OncoTrials. Мониторинг клинических исследований

NCT06545682 (добавлено: Сегодня! )

Phase Ib Study of AlpeliSib with PEmbroLizumab in Patients with MEtastatic Breast CaNcer or MelanomA (SELENA)

Phase Ib Study of AlpeliSib with PEmbroLizumab in Patients with MEtastatic Breast CaNcer or MelanomA (SELENA)

Теги: #Relapsed|Refractory

Локации: MD Anderson Cancer Center; Houston; Texas; United States

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Критерии включения

1. Patients must be 18 years or older.
2. Patients must be willing and able to provide informed consent.
3. In the dose escalation, patients must have histologically documented locally advanced, unresectable, or metastatic melanoma or TNBC that has progressed on treatments that are known to prolong survival or for which no standard treatment is available or refused such therapy. Presence of active brain metastases is not required. Patients with active metastases as defined below can be eligible in the dose escalation.
4. In the dose expansion, patients must have histologically documented locally advanced, unresectable, or metastatic melanoma or TNBC that has progressed on treatments that are known to prolong survival or for which no standard treatment is available or refused such therapy.
1. Melanoma patients without brain metastases who have progressed on an anti-PD-1 or anti-PD-L1-based regimen.
2. Melanoma patients with active and untreated brain metastases who have progressed on an anti-PD-1 or anti-PD-L1-based regimen.
3. TNBC patients (defined as ER /<1%, HER2 0, 1+, 2+, and fluorescence in situ hybridization negative) with active untreated brain metastases. Prior treatment with anti-PD-1/anti-PD-L1 is not required.
5. All patients must have had a brain magnetic resonance imaging (MRI) scan in the previous 28 days to confirm eligibility for the following cohorts:
1. Dose escalation and dose expansion Cohort 1: Confirmed absence of untreated brain metastases in patients with histologically confirmed advanced melanoma. Prior surgery for brain metastases must have been completed at least 4 weeks prior study treatment initiation, whole brain radiation therapy must have been completed at least 3 weeks prior to study treatment initiation, and stereotactic radiosurgery must have been completed within 7 days prior to study treatment initiation.
2. Dose escalation and dose expansion Cohorts 2 and 3: At least one confirmed measurable untreated brain lesion ≥ 0.5 cm and /< 3.0 cm in the longest axis.
6. Has measurable disease based on the RECIST v1.1.
7. Has adequate organ function as defined in Table 2:
8. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 4).
9. Has a life expectancy of at least 12 weeks.
10. Able to swallow and retain orally administered medication.
11. In the dose expansion, patients with EC disease must be willing to provide tissue from a newly obtained, safely accessible core or excisional biopsy lesion at pre-treatment and at least one time point while on study treatment. Correlative biopsies will be optional in the dose escalation portion of the study. Newly obtained biopsy is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of study treatment on Day 1 without intervening systemic therapy.
12. Women of childbearing potential (WOCBP) should have a negative urine pregnancy test within 72 hours prior to receiving the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
13. Alpelisib and pembrolizumab can cause fetal harm when administered to a pregnant woman. Therefore, WOCBP must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of screening through 4 months after the last dose of study treatment. Refer to Pregnancy Assessment Policy MD Anderson Cancer Center (MDACC) Institutional Policy # CLN1114. This includes all female patients between the onset of menses and 55 years unless the patient presents with an applicable exclusionary factor such as one of the following:
1. Postmenopausal (no menses in ≥ 12 consecutive months)
2. History of hysterectomy or bilateral salpingo-oophorectomy
3. Ovarian failure (follicle-stimulating hormone and estradiol in menopausal range and have received whole pelvic radiation therapy)
4. History of bilateral tubal ligation or another surgical sterilization procedure
14. Approved methods of birth control are as follows: hormonal contraception (i.e., birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device, tubal ligation or hysterectomy, patient/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the study and the study treatment washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
15. Male patients with partner(s) of childbearing potential must agree to use adequate contraception from the time of screening through 4 months after the last dose of study treatment.

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Критерии исключения

1. Has a history of or active autoimmune disease, as follows: history of inflammatory bowel disease, history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis /[scleroderma/], systemic lupus erythematosus, autoimmune vasculitis /[e.g., Wegener`s granulomatosis/]), motor neuropathy considered of autoimmune origin (e.g., Guillain-Barré syndrome and myasthenia gravis), or history of autoimmune thyroiditis (patients may be eligible if their current thyroid disorder is treated and stable with replacement or other medical therapy).
2. Has active infection or had a serious general medical condition(s) (such as vascular accident) in the past 6 months.
3. Any unresolved /> Grade 1 toxicity (per CTCAE v5.0) from previous anticancer therapy or previously administered agent at the time of enrollment, except for alopecia and Grade 2 anemia (if hemoglobin is /> 9 g/dL). Note: If the patient received major surgery, he/she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
4. Patients who received chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to starting study treatment.
5. Presence of any clinically significant gastrointestinal abnormality or other condition(s) (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) that may alter absorption such as malabsorption syndrome or major resection of the stomach or substantial portion of the small intestine based on investigator discretion.
6. Previous major surgery within 14 days prior to enrollment.
7. Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease).
8. Established diagnosis of diabetes mellitus type I or uncontrolled type II (based on fasting blood glucose and HbA1c /[see inclusion criteria #4/]).
9. History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis.
10. History of severe cutaneous reaction, such as SJS, erythema multiforme (EM), TEN, or drug reaction with eosinophilia and systemic symptoms (DRESS).
11. Based on average of triplicate 12-lead electrocardiogram (ECG), a mean resting QTc interval using Fridericia formula /> 450 msec for males and /> 470 msec for females at screening or a history of congenital long QT syndrome or QTc /> 480 msec for patients with a bundle branch block.
12. History or evidence of cardiovascular risk including any of the following:
1. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting, or bypass grafting within 6 months prior to enrollment.
2. Class III or IV heart failure as defined by the New York Heart Association functional classification system.
3. Known left ventricular ejection fraction /< 50%.
4. Known cardiac metastases.
13. Poorly controlled hypertension (defined as systolic blood pressure ≥150 mmHg or diastolic blood pressure />100 mmHg based on a mean of three measurements taken at approximately 2-minute intervals).
Note: Initiation or adjustment of antihypertensive medication(s) is permitted if done 30 or more days prior to enrollment.
14. For dose expansion Cohorts 2 and 3 with active brain metastases:
1. Patients must not have any of the following on the screening brain MRI:
* Any untreated brain lesions /> 3.0 cm in size.
* Any brain lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatment-related edema may pose risk to the patient (e.g., brainstem lesions). Patients who undergo local treatment for such lesions may still be eligible for the study.
2. Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of dexamethasone (or equivalent) /> 4 mg.
* Poorly controlled (/> 1/week) generalized or complex partial seizures, or manifestation of neurologic progression due to brain metastases notwithstanding CNS-directed therapy.
15. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient`s participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorder that in the opinion of the treating physician or principal investigator (PI) would interfere with cooperation with the requirements of the trial.
18. Known history of hepatitis B or C or positive test for human immunodeficiency virus.
19. Has received a live vaccine within 30 days of planned start of study treatment.
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; COVID-19 vaccines are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
20. Current use of or anticipated requirement during the study of any prohibited medication(s) (See Section 5.5.2).
21. History of allergic reactions attributed to compounds of similar chemical or biologic composition to alpelisib and pembrolizumab.
22. Pregnant or nursing.

NCT06786533 (добавлено: 2025-01-23)

Clinical Study of Anti-FLT3 CAR-T Cells for the Treatment of Relapsed/refractory AML

Phase 1 Study of Anti-FLT3 Chimeric Antigen Receptor-redirected T Cells in Subjects with Relapsed/refractory Acute Myeloid Leukemia (AML)

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: MD Anderson; Houston; Texas; United States

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Критерии включения

* 18 years of age or older at enrollment
* Subjects with AML unlikely to be cured with currently available therapies. Specifically, the following groups are eligible:
1. Refractory AML: i.e., newly diagnosed AML that after two cycles of intensive chemotherapy has not achieved a complete remission or morphologic leukemia free state by ELN criteria.1 Intensive chemotherapy must have included either the combination of cytarabine and an anthracycline (3+7 or similar) or combination of venetoclax with a hypomethylating agent.
Patients with FLT3 ITD must also have failed treatment with a FLT3 inhibitor and patients with IDH1 or IDH2 mutations must have failed treatment containing ivosidenib or enasidenib respectively (i.e., progression on treatment, or failure to achieve CR after six months of treatment,) OR:
2. AML relapsed following allogeneic stem cell transplantation (including MDS evolved to AML post-allogeneic stem cell transplantation). Note: morphologic relapse is not required; persistent/recurrent disease-associated molecular, phenotypic, or cytogenetic abnormalities (measurable residual disease, MRD) at any time after allogeneic HCT is eligible. OR:
3. AML that has relapsed within 12 months after initial induction and consolidation therapy OR:
4. AML that has relapsed more than 12 months after initial induction but that has failed to achieve CR or morphologic leukemia free state after one reinduction OR:
5. AML after second or subsequent relapse.
* FLT3 expression must be detectable in AML blast by flow cytometric analysis.
* Subjects must have a suitable stem cell transplant donor. Donor may be matched or mismatched and must be found to be suitable according to the institution`s standard criteria. That donor shall be "cleared" for donation by institutional standards prior to administration of HG-CT-1. Adult donors can be either related or unrelated, HLA-matched or partially matched. Matched or partially matched umbilical cord blood donors are also eligible.
* Subjects with relapsed disease after prior allogeneic transplant must be off systemic immunosuppression for at least 1 month at the time of enrollment without GvHD that requires systemic immunosuppression.
* Satisfactory organ functions:
1. Creatinine ≤ 1.6 mg/dl and Creatinine clearance (CrCl) as calculated by the Cockcroft-Gault formula ≥ 60 mL/min.
2. ALT/AST must be ≤ 3 x upper limit of normal unless related to disease.
3. Direct bilirubin /< 2.0mg/dl unless subject has Gilbert`s syndrome (in which case it should be ≤3.0 mg/dL).
4. Left ventricular ejection fraction ≥ 45% as confirmed by echocardiogram or MUGA.
5. DLCO />45% predicted and O2 Saturation /> 90% on room air.
* ECOG Performance status 0-1.
* Written informed consent is given.
* Subjects of reproductive potential must agree to use acceptable birth control methods (as described in protocol Section 4.7).

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Критерии исключения

* Pregnant or lactating (nursing) women.
* Active second malignancy will not be eligible with the following exceptions:
1. Carcinoma in situ of the cervix (which may be considered for enrollment),
2. Indolent, non-metastatic prostate cancer
3. Non melanoma skin cancer
4. Other indolent and controlled malignancies not requiring urgent treatment.
* Subjects with a history of a prior allogeneic stem cell transplantation are excluded if:
1. Subjects are less than 100 days post-transplant OR
2. Subjects have evidence of ongoing active GvHD and are taking immunosuppressive agents (/>0.5mg/kg/methylprednisolone equivalents or other immunosuppression for GvHD treatment) OR
3. Subjects have received DLI within 30 days prior to enrollment.
* Active hepatitis B (HBV) or active hepatitis C (HCV) or any HIV infection. Note: prior HCV that has been appropriately treated or evidence of past HBV infection do not constitute exclusions.
* Concurrent use of systemic steroids at a prednisone dose of greater than 10 mg or equivalent, recent, or current use of inhaled steroids is not exclusionary.
* Concurrent use of immunosuppressant medications such as calcineurin inhibitors, methotrexate, or alemtuzumab.
* Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the site Pl would pose an unacceptable risk to the subject.
* Active or uncontrolled viral, bacterial, or fungal infection. May be receiving ongoing therapy for controlled infection.
* Subjects with signs or symptoms indicative of active CNS involvement. A CNS evaluation shall be performed as clinically appropriate to rule out CNS involvement. Subjects with adequately treated CNS leukemia are eligible.
* Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
* Hyperleukocytosis (/>50,000 blasts/µL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy.
* Patients with Acute Promyelocytic Leukemia are not eligible.

NCT06783790 (добавлено: 2025-01-22)

Avapritinib Combined With Azacitidine and Venetoclax in the Treatment of Relapsed AML After Allo-HSCT

An Exploratory Clinical Study of the Safety and Efficacy of Avapritinib Combined With Azacitidine and Venetoclax in the Treatment of Relapsed Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

Теги: #Relapsed|Refractory

Локации: Institute of Hematology & Blood Diseases Hospital; Tianjin; China

NCT06504459 (добавлено: 2025-01-22)

Venetoclax in Combination With Cladribine and Cytarabine Alternating With Azacitidine Plus Venetoclax for the Treatment of Newly Diagnosed Monocytic AML and Active Signaling Mutated AML

A Phase II Study of Venetoclax (ABT-199) in Combination With Cladribine and Low-Dose Cytarabine Alternating With Azacitidine Plus Venetoclax in Newly Diagnosed Monocytic AML and Active-Signaling Mutated AML

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: OHSU Knight Cancer Institute; Portland; Oregon; United States

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Критерии включения

* Ability to comprehend the investigational nature of the study and provide informed consent (i.e., participant or legally authorized representative /[LAR/]). Written informed consent must be obtained prior to any study-specific procedures or interventions
* Eligible AML patients of all races and ethnic groups will be considered for participation, irrespective of gender identity
* Newly diagnosed, histologically confirmed monocytic AML, as defined by World Health Organization (WHO), or active signaling mutated AML defined as AML with mutation(s) to N/KRAS, FLT3 ITD/TKD, NF1, PTPN11 or CBL
* Ineligible for standard of care induction therapy using intensive chemotherapy (IC) or unwilling to undergo IC induction therapy. Ineligible for IC is defined as
* ≥ 75 yrs of age; OR
* 18-74 yrs of age with one of the following:
* Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2 at screening
* Severe cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
* Severe pulmonary disorder (e.g., diffuse capacity of the lung for carbon monoxide /[DLCO/] ≤ 65% or forced expiratory volume in 1 second /[FEV1/] ≤ 65%)
* Creatinine clearance /< 45 ml/min (calculated by the Cockcroft-Gault equation)
* Hepatic disorder with total bilirubin /> 1.5 x upper limit of normal (ULN)
* Any other comorbidity that the treating physician judges to be incompatible with IC
* If ≥ 75 yrs of age, the following organ function values must be met and ECOG must be 0 to 2 at screening:
* Creatinine clearance (calculated with the Cockcroft-Gault equation) ≥ 30 ml/min
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (Unless due to leukemic infiltration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase /[SGOT/]) or alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase /[SGPT/]) ≤ 3 x ULN (Unless due to leukemic infiltration) (With the exception of documented Gilbert`s syndrome or similar conditions. Liver function testing (LFT) and timepoints may be added, as clinically indicated, in such cases)
* Note: In cases of confirmed leukemic organ involvement, exceptions may be made
* Willing and able to provide bone marrow (BM) samples, including BM samples for research use only analysis
* Willing and able to accept supportive and prophylactic care for hematologic toxicities, infection, and immediate sequalae
* Willingness to adhere to (a) study schedule of activities; (b) requirements for bio samples collections; and (b) lifestyle restrictions while on-treatment
* Negative urine pregnancy test at screening and within 24 hours of cycle 1 day 1 (C1D1) for persons of childbearing potential (PCBP). Serum pregnancy testing will be used for confirmation in cases of equivocal results. Pregnancy is exclusionary because the agents used in this study have the potential for teratogenic or abortifacient effects
* Willingness to comply with study requirements for contraception within the specified timeframe, as follows:
* Sperm producing participants who are active with PCBP must use approved contraception from C1D1 to 30 days, 3 months, or 6 months, after the last dose of venetoclax (30 days), azacitidine (3 months), cladribine (6 months), or cytarabine (6 months), whichever is later in time
* PCBP who are sexually active with sperm-producing persons must use contraception from C1D1 to 30 days after the last dose of venetoclax or to 6 months after the last dose of azacitidine, cladribine, or cytarabine, whichever is later in time

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Критерии исключения

* Symptomatic central nervous system involvement with AML
* Prior treatment for AML, with the exception of cytoreduction for proliferative disease (per institutional protocol) with any of the following: Hydroxyurea, hematopoietic growth factors, leukapheresis
* Another active malignancy within the previous 5 years of C1D1
* Investigational therapy within 28 days of C1D1, or within 5 half-lives or longer, if known
* Recent and significant medical interventions, such as major surgery within 28 days or stem cell transplant within 100 days (and without active treatment for graft versus host disease /[GVHD/]) of C1D1. Standard of care procedures for patients with hematologic malignancies, such as biopsies and lumbar punctures, are not exclusionary
* Hypersensitivity to any of the components of the investigational regimen (i.e., cladribine, cytarabine, venetoclax, azacitidine) or any excipients in the formulations
* Treatment based on agents targeting or inhibiting BCL-2 (for other, prior indication/malignancy) within the previous 5 years
* History of dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
* Use of drugs with documented drug-drug interaction toxicities with the study drugs
* Strong or moderate CYP3A4 inducers or inhibitors within 2 days or 3 half lives whichever is longer, prior to C1D1 are exclusionary. Dose adjustments and other modifications may be considered if the wash-out period has not been met, with the approval of the investigator and the research pharmacy
* Uncontrolled infection. Participants with controlled infection must be afebrile and hemodynamically stable for at least 72 hours prior to C1D1 and must be amenable to alternate treatment if current treatment will interact with investigational regimen
* Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Enrollment of individuals with evidence of chronic HBV or HCV infection will be considered on a case-by-case basis by the principal investigator
* Individuals with serology positive for human immunodeficiency virus (HIV) and under active treatment with highly active antiretroviral therapy (HAART) (or another therapy that may interfere with metabolism of study agents)
* Pregnancy at enrollment or unwillingness to stop breastfeeding. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding be discontinued from start of treatment until 1 week after the final dose of any study drug
* Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, unstable cardiac or pulmonary function or acute insufficiency (e.g., symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia), or psychiatric illness or social situation that could limit compliance with study requirements

NCT06773208 (добавлено: 2025-01-15)

A Study of Azacitidine and Venetoclax in People With Acute Myeloid Leukemia (AML)

A Phase 2 Study of Azacitidine and Venetoclax to Treat Acute Myeloid Leukemia Patients With Measurable Residual Disease Before an Allogeneic Stem Cell Transplant

Теги: #Relapsed|Refractory

Локации: Memorial Sloan Kettering at Basking Ridge (All Protocol Activities); Basking Ridge; New Jersey; United States,Memorial Sloan Kettering Bergen (All Protocol Activities); Montvale; New Jersey; United States,Memorial Sloan Kettering Cancer Center (All Protocol Activities); New York; New York; United States,Memorial Sloan Kettering Monmouth (All Protocol Activities); Middletown; New Jersey; United States,Memorial Sloan Kettering Nassau (All Protocol Activities); Rockville Centre; New York; United States,Memorial Sloan Kettering Suffolk-Commack (All Protocol Activities); Commack; New York; United States,Memorial Sloan Kettering Westchester (Limited Protocol Activities); Harrison; New York; United States

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Критерии включения

* 1. Adult patient ≥18 years of age at the time of signing the informed consent form (ICF). Legal Authorized Representatives (LAR) are permitted.
2. Patient is willing and able to adhere to the study visit schedule and other protocol requirements.
3. Patient has a confirmed diagnosis of de-novo AML (non-APL) as per World Health Organization (2022) guidelines. All (non-APL) subtypes of AML are permitted, irrespective of ELN risk category or mutational status.
4. Patient has received 2 cycles of intensive chemotherapy (either induction + consolidation or 2 induction cycles).
5. Patient is in a morphologic remission, defined as less than 5% percent blasts seen by aspirate differential (or immunohistochemistry if no aspirate available) from bone marrow biopsy.
6. Patient and is either in CR, or CR with partial count recovery, either CRi/CRh///^1.
1CR= BM with /<5% blasts, absence of circulating blasts; absence of extramedullary disease, absolute neutrophil count (ANC) ≥ 1000 cells/µL and platelet (PLT) count ≥ 100,000/µL. CRh = CR with ANC 500-1000 cells/µL and PLT 50,000-100,000 /µL. CRi = CR without meeting CRh criteria (residual neutropenia or thrombocytopenia).
7. Patient has positive measurable residual disease (MRD) at or above a level of 0.1%, by flow cytometry or in molecular cases (NPM1 mutated or one of the CBF translocations) RT-qPCR reported at or above 0.01%, as described above (see section 3.6).
8. Patient is eligible for intensive chemotherapy and immediate allogeneic transplant, with intention to proceed to transplant after trial intervention.
9. Patient has an ECOG performance status of ≤3 10. Patient has adequate organ function defined as:
1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
2. Serum total bilirubin /< 1.5 x ULN (or direct bilirubin normal in subjects with total bilirubin /> 1.5 ULN). Except in cases of Gilbert`s disease.
3. Creatinine clearance greater than 30 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation.
11. Absence of active uncontrolled infection, heart failure or severe psychiatric or neurological disease.
12. Females of childbearing potential may participate provided they have a negative serum pregnancy test at screening and a negative serum OR urine pregnancy test within two weeks of starting on treatment.
13. Females of reproductive potential should use effective contraception during the study, and for 6 months after last dose of azacitidine. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after.
Exclusion Criteria:
1. Patients with acute promyelocytic leukemia (APL) or relapsed/refractory AML 2. Blast crisis of chronic myeloid leukemia 3. Patient with 5% blasts or more by flow or bone marrow aspirate differential (or IHC if no aspirate available) 4. Patient without count recovery (CBC less than CRh) 5. Patient has received previous therapy with a venetoclax containing regimen. 6. Patient has presence of any other condition that may increase the risk associated with study participation, and in the opinion of the investigator, would make the patient inappropriate for entry into the study.
7. Patient has active uncontrolled systemic fungal, bacterial, or viral infection.
8. Patient had recent, significant venous or arterial thrombotic event that would necessitate full anticoagulation or dual anti-platelet therapy, including PE within 30 days prior to start of treatment or insertion of drug eluting stent within 6 months prior to start of treatment. Chronic indications for anticoagulation such as atrial fibrillation, can be included if CHADS2 score below 4.
9. Patient has mechanical heart valve. 10. Patient had recent significant hemorrhagic episode, at the discretion of investigator.
11. Patient has significant active cardiac disease within 6 months prior to start of study treatment.
12. Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
13. Female subject who is pregnant or lactating.

NCT06765876 (добавлено: 2025-01-10)

CART123 T Cells in Relapsed or Refractory CD123+ Hematologic Malignancies: a Dose Escalation Phase I Trial

Safety and Efficacy of Anti-CD123 Chimeric Antigen Receptor-Modified Autologous T Cells (CART123) in Patients with Relapsed/Refractory CD123+ Hematologic Malignancies: a Dose Escalation, Open-Label, Phase I Study

Теги: #Relapsed|Refractory

Локации: Ustav hematologie a krevni transfuze / Institute of Hematology and Blood Transfusion; Prague; Czech Republic

NCT06762132 (добавлено: 2025-01-08)

A Clinical Study to Explore the Safety and Efficacy of CD33 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia

A Clinical Study to Explore the Safety and Efficacy of CD33 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia

Теги: #Relapsed|Refractory

Локации: The first affiliated hospital of medical college of zhejiang university; Hangzhou; Zhejiang; China

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Критерии включения

* 1. Male or female, age ≥ 18 years old;
* 2. CAR-T cells can be prepared normally, or who have failed to prepare autologous CAR-T cells (including the number of autologous lymphocytes /<1×10/^9 or the expansion during the preparation process is insufficient or cannot reinfusion);
* 3. Patients diagnosed with CD33 positive acute myeloid leukemia (AML) through histological or immunological examination，and CD33 positive expression rate />80%;
* 4. Complies with the 2016 WHO classification for AML diagnosis and meets the diagnostic criteria for recurrence and refractory acute myeloid leukemia in the "Chinese Guidelines for the Diagnosis and Treatment of relapsed and refractory acute myeloid leukemia (2017 edition)", and currently there are no clinically relevant treatments or suitable clinical trials for registration:
* a) Diagnostic criteria for recurrent AML: After complete remission (CR), leukemia cells reappear in peripheral blood or primitive cells in bone marrow/>0.050 (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy) or leukemia cell infiltration appears outside the bone marrow;
* b) Diagnostic criteria for refractory AML: initial treatment cases that have failed to respond to two courses of standard protocol treatment; Patients who relapse within 12 months after consolidation and intensive treatment after CR; Patients who relapse after 12 months but fail conventional chemotherapy; Patients with 2 or more relapses; Persistent extramedullary leukemia;
* 5. The number of primitive cells (promyelocytes and/or promyelocytes) in the bone marrow /> 5% (morphology) and/or /> 1% (flow cytometry detection);
* 6. Total bilirubin ≤ 51 μmol / L, ALT and AST ≤ 3 times of the upper limit of normal value, serum creatinine ≤ 176.8 μmol / L；
* 7. Echocardiography shows left ventricular ejection fraction (LVEF) ≥ 50%;
* 8. There is no active pulmonary infection, and the oxygen saturation during air inhalation is more than 92%;
* 9. The estimated survival time is more than 3 months;
* 10. ECOG score was 0-2;
* 11. Pregnant/lactating women, or male or female patients who have fertility and are willing to take effective contraceptive measures at least 6 months after the last cell infusion during the study period;
* 12. Those who voluntarily participated in this trial and provided informed consent

NCT06484062 (добавлено: 2025-01-08)

Testing the Anti-cancer Drug, Cirtuvivint, and Its Combination With ASTX727 to Improve Outcomes in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndromes

A Phase I Study Evaluating the Safety of Cirtuvivint as Monotherapy and in Combination With ASTX727 and ASTX727 + Venetoclax in Patients With Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: Dana-Farber - Harvard Cancer Center LAO; Boston; Massachusetts; United States

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Критерии включения

* In Cohorts I and II, patients must have R/R AML and MDS (venetoclax naïve or venetoclax exposed)
* Relapsed AML is defined as the appearance of 5% or greater myeloblasts in the bone marrow or peripheral blood after achieving a complete remission (CR), CR with partial hematologic recovery (CRh), or CR with incomplete hematologic recovery (CRi). Patients with mutations in FLT3, IDH1 or IDH2 must have failed or been intolerant of a Food and Drug Administration (FDA) approved FLT3, IDH1 or IDH2 inhibitor before enrolling on study
* Refractory AML is defined as failure to achieve a CR, CRh, or CRi after one of the following regimens: (i) Two cycles of intensive induction chemotherapy with a cytarabine containing regimen (e.g., 7+3, mitoxantrone, etoposide, cytarabine /[MEC/], high-dose cytarabine /[HIDAC/], etc.) or, (ii) Two cycles of hypomethylating agent (HMA)/venetoclax or low-dose cytarabine (LDAC)/glasdegib or, (iii) Four cycles of HMA monotherapy
* Relapsed MDS is defined as: (i) Intermediate, high, or very high-risk disease by International Prognostic Scoring System-Revised (IPSS-R) and, (ii) Any relapse after achieving any 2023 IWG MDS defined response
* Refractory MDS is defined as: (i) Intermediate, high, or very high-risk disease by IPSS-R and /> 5% blasts in the bone marrow or peripheral blood, (ii) Failure to achieve a response (as per IWG 2006 criteria) after four cycles of HMA monotherapy, or (iii) Two cycles of HMA + venetoclax
* In Cohort III, patients must have prior untreated high-risk MDS
* MDS with /> 5% blasts in the bone marrow or peripheral blood AND
* IPSS-R high or very high-risk disease OR
* Molecular International Prognostic Scoring System (IPSS-M) high or very high-risk disease
* No prior use of deoxyribonucleic acid methyltransferase inhibitor (DNMTi) therapy with the exception of one single cycle of DNMTi. Prior use of erythropoiesis stimulating agents (ESA), thrombopoietin agonists, lenalidomide, and luspatercept are allowed
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of SM08502 (cirtuvivint) in combination with ASTX727 in patients /< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
* Total bilirubin ≤ 2 x institutional upper limit of normal (ULN) (unless bilirubin rise is due to Gilbert`s syndrome or of non-hepatic origin; in that case a cut off of ≤ 4 × institutional ULN will be used)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase /[SGOT/])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase /[SGPT/]) ≤ 3 x institutional ULN (unless considered due to organ involvement by the patient`s myeloid malignancy; in that case a cut off of ≤ 5 x institutional ULN will be used)
* Glomerular filtration rate (GFR) ≥ 45 mL/min/1.73m/^2
* If female, patient must be either:
* Postmenopausal (surgically sterile or age /> 55 years with no menses for 12 or more months without an alternative medical cause or age equal to 55 or less with no menses for 12 or more months without an alternative medical cause and a follicle stimulating hormone /[FSH/] level /> 40 IU/L); or
* Of children bearing potential. These patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Patient must agree to have a negative urine or serum beta-human chorionic gonadotropin (HCG) test result during screening and repeated within 7 days prior to study drug (local labs are allowed) to be eligible
* The effects of SM08502 (cirtuvivint) and ASTX727 on the developing human fetus are unknown. For this reason, and because these agents are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and during the treatment therapy. Women of childbearing age should agree to use adequate contraception for 7 months after completion of SM08502 (cirtuvivint) administration. For ASTX727, adequate contraception must continue for at least 6 months after last dose of ASTX727. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of the study and at least 4 months after the last dose of SM08502 (cirtuvivint) and 3 months after last dose of ASTX727. Women who are lactating must refrain from breastfeed during the study and at least for two weeks after last dose of ASTX727
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

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Критерии исключения

* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities /> grade 1) with the exception of alopecia or abnormal blood counts
* Patients who are receiving any other investigational agents
* Systemic anti-leukemic therapy within 14 days of first day of study treatment. If on venetoclax, then a wash-out period of at least five times the half-life of the treatment. Exceptions: No wash-out required for intrathecal chemotherapy, hydroxyurea, cytarabine (Ara-C), or palliative radiation therapy to painful sites of leukemic disease
* Patient is receiving known inhibitors or activators of flavin-containing monooxygenases (FMO1 or FMO3), and these cannot be stopped at least 5 days prior to SM08502 (cirtuvivint) treatment start. Known inhibitors of FOMO are chlorpromazine and imipramine
* Patient is receiving strong inhibitors or strong inducers of CYP3A4/5 and these cannot be stopped at least 5 days prior to SM08502 (cirtuvivint) treatment start
* Strong inhibitors include grapefruit juice or grapefruit/grapefruit related citrus fruits (e.g., Seville oranges, pomelos), ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir, nefazodone, lopinavir, troleandomycin, mibefradil, and conivaptan. Examples may be found at the FDA website. Refer to the prescribing information of concomitant medications if in doubt or consult the sponsor for guidance
* Strong inducers include phenobarbital, rifampin, phenytoin, carbamazepine, rifabutin, rifapentin, clevidipine, and St. John`s Wort. Examples may be found at the FDA website. Refer to the prescribing information of concomitant medications if in doubt or consult the sponsor for guidance.
* While moderate inhibitors or moderate inducers of CYP3A4/5 are not an exclusion criterium for the trial, it is preferred that moderate inhibitors or moderate inducers of CYP3A4/5 be replaced prior to the first dose of SM08502 (cirtuvivint) and during study conduct where this is possible.
* Moderate inhibitors include erythromycin, ciprofloxacin, verapamil, diltiazem, atazanavir, fluconazole, darunavir, delavirdine, amprenavir, fosamprenavir, aprepitant, imatinib, tofisopam, and cimetidine. Examples may be found at the FDA website. Refer to the prescribing information of concomitant medications if in doubt or consult the sponsor for guidance
* Moderate inducers include bosentan, efavirenz, etravirine, modafinil, and nafcillin. Examples may be found at the FDA website. Refer to the prescribing information of concomitant medications if in doubt or consult the sponsor for guidance
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to SM08502 (cirtuvivint) or ASTX727
* Chronic, active hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: patients with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface /[HBs/] antigen negative, anti-HBs antibody positive and anti-hepatitis B core /[HBc/] antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate. Patients who had prior HCV that has been definitively treated with negative HCV viral load prior to study initiation and no evidence of cirrhosis, are allowed to participate. If there is no known history of HBV infection no HBV studies need to be obtained. If there is no known history of HCV infection, no HCV studies need to be obtained
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
* Pregnant and lactating women are excluded from this study because SM08502 (cirtuvivint) is a small molecule inhibitor of CLK DYRK with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SM08502 (cirtuvivint), breastfeeding should be discontinued if the mother is treated with SM08502 (cirtuvivint). These potential risks may also apply to other agents used in this study
* Patients with acute promyelocytic leukemia
* Subject has symptomatic central nervous system (CNS) involvement with AML
* Patient has immediate life-threatening, severe complications of their myeloid malignancy such as uncontrolled bleeding and/or uncontrolled infection
* Patient has significant active cardiac disease within 6 months prior to the start of study treatment, including uncontrolled New York Heart Association (NYHA) class III or IV congestive heart failure; acute coronary syndrome (ACS); and/or stroke
* Left ventricular ejection fraction (LVEF) /< 40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan obtained within 30 days prior to the start of study treatment
* Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally. Patient needs to be able to swallow pills
* Patient has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
* Subject has corrected QC (QTc) interval (i.e., Fridericia`s correction /[QTcF/]) ≥ 480 ms or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening

NCT06313437 (добавлено: 2025-01-03)

Revumenib in Combination With 7+3 + Midostaurin in AML

A Phase I Trial of Revumenib in Combination With 7+3 (7 Days of Cytarabine and 3 Days of Daunorubicin) + Midostaurin Induction Chemotherapy for the Frontline Treatment of NPM1 and FLT3 Mutated AML

Теги: #FLT3 mutation , #Newly diagnosed

Локации: Brigham and Women`s Hospital; Boston; Massachusetts; United States,Dana-Farber Cancer Institute; Boston; Massachusetts; United States

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Критерии включения

* Patients with AML who are newly diagnosed according to the WHO 2022 Classification and previously untreated except for hydroxyurea. ATRA pretreatment for suspected APL for less than 5 days is allowed. Eligible patients with AML arising from an antecedent hematologic disease (AHD) including MDS, may have been treated for their prior hematologic disease (except for allogenic transplant).
* Patients must be ≥ 18 and /< 75 years old.
* Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.
* Presence of FLT3-ITD and/or TKD mutation(s) AND NPM1 mutation in bone marrow or peripheral blood
* Dose escalation phase only: Presence of any of the following adverse risk genetic characteristics:
* 2022 ELN adverse risk genetic features:
* t(6;9)(p23.3;q34.1)/DEK::NUP214
* t(v;11q23.3)/KMT2A-rearranged
* t(9;22)(q34.1;q11.2)/BCR::ABL1
* t(8;16)(p11.2;p13.3)/KAT6A::CREBBP
* inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/ GATA2, MECOM(EVI1)
* t(3q26.2;v)/MECOM(EVI1)-rearranged
* -5 or del(5q); -7; -17/abn(17p)
* Complex karyotype, monosomal karyotype
* Mutations in either one of these genes: ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2
* Mutated TP53
* NPM1 + FLT3-ITD + DNMT3A mutation
* LVEF ≥ 50% by MUGA or ECHO at screening.
* Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 60 mL/min; determined by the Cockcroft Gault formula.
* Adequate liver function as demonstrated by:
* aspartate aminotransferase (AST) ≤ 2.5 × ULN/*
* alanine aminotransferase (ALT) ≤ 2.5× ULN/*
* total bilirubin ≤ 1.5 × ULN/* /* Unless considered due to leukemic organ involvement. Note: Subjects with Gilbert`s Syndrome may have a total bilirubin /> 1.5 × ULN per discussion with the Sponsor-Investigator
* Resolution of adverse reactions to prior drug therapy (such as hydroxyurea) to ≤ grade 1
* Eligible for intensive cytarabine/daunorubicin (7+3) chemotherapy based on the opinion of the treating physician.
* Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.
* Females of childbearing potential (i.e., not postmenopausal for at least 1 year or not surgically sterile) must have negative results by a serum or urine pregnancy test performed within 7 days of day 1.
* Ability to understand and the willingness to sign a written informed consent document. (Providing consents in as many languages as possible is encouraged)
* Consolidation should occur between 1-4 weeks following count recovery after induction and remission (must be confirmed by labs to document maximal response) is established. Subjects will receive medium intensity cytarabine -based consolidation in combination with midostaurin and revumenib if the following criteria are fulfilled.
* an induction response /< 5% blasts in the bone marrow and ANC />1000 and PLT />75000 for whom documented path report is submitted.
* sufficiently fit (performance status /<3)
* resolution of any adverse reactions to no greater than grade 1 severity

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Критерии исключения

* Subject has acute promyelocytic leukemia, inversion (16), t(8;21) AML as described below. Contact Sponsor-Investigator with questions. Inversion 16 and t(8;21): CBF chromosomal abnormalities may be assessed by molecular (PCR), metaphase cytogenetics, or FISH.
* Subject has known active CNS involvement with AML.
* Subject has received a strong CYP3A4 inducer (APPENDIX C) within 7 days prior to the initiation of study treatment
* Strong CYP3A4 inhibitors (APPENDIX C) are contraindicated except strong CYP3A4 inhibitor antifungal azole medications (systemic itraconazole, ketoconazole, posaconazole, voriconazole). For strong CYP3A4 inhibitor antifungal azole medications, the starting dose of revumenib has to be adjusted (Table 1).
* QTc using Fridericia`s correction /[QTcF/]) /> 450 msec. Drugs that prolong QTc should be avoided if possible. A list of common QTc prolonging drugs and alternatives that are not QTc prolonging can be found in APPENDIX D.
* Subject has tested positive for HIV (due to potential drug-drug interaction between antiretroviral medications and Midostaurin/revumenib). Note: HIV testing is not required.
* Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV /[i.e., HBs Ag-, and antiHBs+/] are allowed.
* Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment.
* Subject has a cardiovascular disability status of New York Heart Association Class ≥ 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
* Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study.
* Subject has chronic respiratory disease that requires continuous oxygen use.
* Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
* Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to uncontrolled systemic infection.
* Subject has a history of other malignancies prior to study entry, with the exception of:
* Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
* Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
* Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
* Prior malignancies treated with (surgery+/- chemotherapy+/- radiation) that have remained disease free for at least two years after completion of therapy
* Subject treated with any form of chemotherapy, immunotherapy, or investigative agent within 1 month of enrollment.
* Patients who have had prior exposure to a menin inhibitor.

NCT06575296 (добавлено: 2024-12-28)

Revumenib for the Treatment of Acute Leukemia in Patients Post-Allogeneic Stem Cell Transplant

A Phase I Study of SNDX 5613 (Revumenib) as Post-Transplant Maintenance After Allogeneic Hematopoietic Cell Transplant in Patients With KMT2A-Rearranged or NPM1-Mutated Acute Leukemia

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: City of Hope Medical Center; Duarte; California; United States

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Критерии включения

* PATIENTS WHO ARE SCHEDULED TO UNDERGO HEMATOPOIETIC CELL TRANSPLANTATION (HCT) OR THOSE WHO HAVE UNDERGONE HCT: Documented informed consent of the participant and/or legally authorized representative
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Agreement to allow the use of archival tissue from diagnostic tumor biopsies; if unavailable, exceptions may be granted with study principal investigator (PI) approval
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participant is willing and able to adhere to the study visit schedule and other protocol requirements
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Age: />= 2 years
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Have a date for transplant within the next 4 weeks or have received transplant within the last 4 months
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participant was diagnosed with an acute leukemia as defined by the World Health Organization (WHO) 5th edition criteria for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or acute leukemia with ambiguous lineage
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participant must meet one of the following disease characteristics:
* Confirmed NPM1m AML with at least one of the following additional characteristics
* FLT3-ITD co-mutation
* Pre-transplant MRD+ disease by flow cytometry or real time polymerase chain reaction (qPCR)
* Requires more than one AML induction regimen to acquire complete response (CR)1
* In second or later complete remission
* Confirmed KMT2Ar acute leukemia obtained by fluorescence in situ hybridization (11q23 MLL-break apart fluorescence in situ hybridization /[FISH/]) or next-generation sequencing (NGS)
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Any donor (sibling, unrelated, mismatched related/unrelated, cord and haploidentical) or graft source (peripheral blood /[PB/] stem cell or bone marrow /[BM/]) will be included
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Conditioning regimen: investigator`s choice based on center guidelines
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: GVHD prophylaxis: investigator`s choice based on center guidelines
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Patients receiving menin inhibitors prior to alloHCT are eligible
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Negative serum pregnancy test for female patients of childbearing potential who have already undergone alloHCT
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: If a female of childbearing potential, must be willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: If male of childbearing potential, must agree to use barrier contraception from the time of enrollment through 120 days following the last study drug dose
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for /> 1 year (women only)
* PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Participant has an Eastern Cooperative Oncology Group (ECOG) =/< 2 or Karnofsky Performance Status (KPS) />= 70, or a Lansky Performance Score of />= 70 (if aged /< 18 years)
* PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Participant must be eligible for alloHCT by City of Hope (COH) standard operating procedure (SOP) guidelines
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Patients should be in complete remission (CR) by day + 30 (± 7 days) post-HCT BM biopsy
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: No evidence of active or uncontrolled infection at the time of start of revumenib therapy
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant has an ECOG =/< 2 or KPS />= 70, or Lansky Performance Score of />= 70 if aged /< 18 years
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: No active grade 2-4 acute GVHD (prednisone dose of =/< 0.5 mg/kg daily is allowed)
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Hemoglobin (Hgb) />= 9. Transfusion or growth factors are not allowed to achieve these levels
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Platelets />= 75 thousand (k). Transfusion or growth factors are not allowed to achieve these levels
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Patients must be fully engrafted after HCT, defined as absolute neutrophil count (ANC) />= 500 for 3 days. Patients may NOT be given granulocyte colony-stimulating factor (GCSF) to meet eligibility criteria; however, they may receive GCSF after start of treatment
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: No morphologic evidence of relapse post-HCT (pre-HCT MRD+ is)
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant is between day + 50 and + 150 after first alloHCT with no morphologic evidence of relapse post-HCT
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Total bilirubin =/< 1.5 x upper limit of normal (ULN) (unless considered to be due to Gilbert`s syndrome)
* Note: Participants who are /< 75 years of age may have a bilirubin of =/< 3.0 x ULN. Patients with abnormal liver function tests (LFTs) in the context of active GVHD will not be included
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Aspartate aminotransferase (AST) =/< 2.5 x ULN
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Alanine aminotransferase (ALT) =/< 2.5 x ULN
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: QTc using Fridericia`s correction (QTcF) =/< 450 msec (males) or =/< 470 msec (females)
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Ejection fraction (EF) of />= 50% by echocardiogram or multigated acquisition (MUGA) scan
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Creatinine clearance of />= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula

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Критерии исключения

* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Prior diagnosis of acute promyelocytic leukemia
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participants who are unable to take a strong CYP3A4 inhibitor such as voriconazole or posaconazole. Note: Patients must be taking a strong CYP3A4 inhibiting antifungal at least 7 days prior to starting revumenib cycle 1
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Patients requiring the concurrent use of medications known or suspected to prolong the QT/corrected QT (QTc) interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (e.g., diphenhydramine, famotidine, ondansetron, bactrim, tacrolimus, azoles)
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: History of or any concurrent condition, therapy, laboratory abnormality, or allergy to excipients that in the investigator`s opinion might confound the results of the study, interfere with the patient`s participation for the full duration of the study, or is not in the best interest of the patient to participate
* PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
* PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Participant has detectable human immunodeficiency virus (HIV) viral load within the previous 6 months (must have viral load testing prior to study enrollment if participant has a known history of HIV 1/2 antibodies)
* PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Active uncontrolled hepatitis B or C, defined as hepatitis B or C virus (HBV/HCV) surface antigen positive and HBV/HCV core antibody positive, with positive HBV/HCV deoxyribonucleic acid (DNA), or HBV/HCV positive core antibody alone with positive HBV/HCV DNA
* PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Hepatitis C, defined as positive HCV antibody with reflex to positive HCV ribonucleic acid (RNA)
* PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Other active malignancy; patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Active grade II-IV acute GVHD, chronic GVHD (moderate or severe) and/or requiring systemic steroids with prednisone dose equivalent of />= 0.25mg/kg within 4 weeks of revumenib administration
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participants who are unable to take a strong CYP3A4 inhibitor such as voriconazole or posaconazole. Note: Patients must be taking a strong CYP3A4 inhibiting antifungal at least 7 days prior to starting revumenib in cycle 1
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Patients requiring the concurrent use of medications known or suspected to prolong the QT/QTc interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (e.g., diphenhydramine, famotidine, ondansetron, bactrim, tacrolimus, and azoles)
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Female participant who is pregnant or lactating
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant has a malabsorption syndrome or other condition that precludes enteral route of administration
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant has chronic respiratory disease that requires continuous oxygen, or significant renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect participation in this study
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Cardiac disease: any of the following within the 6 months prior to study entry:
* Myocardial infarction
* Uncontrolled/unstable angina
* Congestive heart failure (New York Heart Association Classification class />= II)
* Life-threatening or uncontrolled arrhythmia
* Cerebrovascular accident
* Transient ischemic attack
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Gastrointestinal disease:
* Any gastrointestinal issue of the upper gastrointestinal (GI) tract likely to affect oral drug absorption or ingestion (e.g., gastric bypass, gastroparesis, etc.)
* Cirrhosis with a Child-Pugh score of B or C
* CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: GVHD: Signs or symptoms of acute or cGVHD /> grade 0 within 4 weeks of enrollment. Patients may be on physiological doses of steroids

NCT06656494 (добавлено: 2024-12-28)

ICP-248 in Combination with Azacitidine in Treatment-Naïve Subjects with Acute Myelogenous Leukemia(AML) or Previously Treated Relapsed/Refractory Subjects with Acute Myelogenous Leukemia(R/R AML).

A Phase 1 Study of ICP-248 in Combination with Azacitidine in Treatment-Naïve Subjects with Acute Myelogenous Leukemia Who Are Not Eligible for Standard Anthracycline-Based Induction or Previously Treated Relapsed/Refractory Subjects with Acute Myelogenous Leukemia.

Теги: #Relapsed|Refractory

Локации: The First Affiliated Hospital, Zhejiang University School of Medicine; Hangzhou; Zhejiang; China

NCT06746519 (добавлено: 2024-12-27)

BN104 in Combination With Chemotherapy or Targeted Agents for Acute Myeloid Leukemia

A Phase I/II , Multicenter, Open Label Clinical Study Evaluating the Safety, Pharmacokinetics, and Efficacy of the Combination of the Menin Inhibitor BN104 for the Treatment of Patients With Acute Myeloid Leukemia

Теги: #Relapsed|Refractory

Локации: The First Affiliated Hospital of Soochow University; Suzhou; Jiangsu; China

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Критерии включения

* Have been fully informed about the study and have voluntarily signed the ICF;
* Patients with newly diagnosed primary AML according to the 2022 World Health Organization (WHO) criteria (Groups A and B) or patients with relapsed/refractory AML who have been previously treated with menin inhibitor monotherapy (Group C) and have an intermediate or poor prognosis according to the 2022 ELN Risk Stratification, as well as a defined combination of NPM1 mutation or NUP98 rearrangement or KMT2A rearrangement
* Peripheral blood leukocyte count ≤ 25 x 109/L (limited to patients enrolled in groups B and C, where hydroxyurea is allowed to control peripheral blood leukocyte count)
* Aged 18 years or older;
* ECOG (GroupA and B:0,1,2; GroupC:0,1,2,3)
* For patients in group B, unfit for intensive chemotherapy is defined as:≥75 years of age or;Age ≥18 years and age /<75 years with any of the following co-morbidities;ECOG score of 2 or 3;Cardiac history: congestive heart failure requiring treatment, or ejection fraction ≤50%, or chronic stable angina;DLCO ≤ 65% or FEV1 ≤ 65%;Creatinine clearance ≥30 ml/min and /<45 ml/min;Liver injury total bilirubin /> 1.5 x ULN but ≤ 3 x ULN.
* For patients in group C, previous failed treatment with menin inhibitors is required;
* adequate hepatic, renal, and cardiac function, as defined:Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal range (ULN);Total bilirubin ≤ 1.5 x ULN/* and in patients with Gilbert disease, total bilirubin ≤ 3 x ULN;Creatinine clearance ≥ 45 ml/min/* as estimated by the Cockcroft-Gault formula (if /<45 ml/min, enrollment is allowed if creatinine ≤ 130 µmol/L); Left ventricular ejection fraction ≥ 45%/*; Note: In Phase II studies, ALT or AST may be relaxed to ≤5 x ULN if the investigator assesses that the elevated ALT or AST is due to leukemia invasion of the liver;For patients /<75 years of age enrolled in Group B, total bilirubin ≤ 3 × ULN, creatinine clearance ≥ 30 ml/min, or left ventricular ejection fraction /< 50% are allowed;
* for patients with D-dimer test result /> 5×ULN in the screening period, relevant tests (e.g. review of coagulation function after a certain time interval, ultrasound of deep veins of the lower limbs, etc.) are required to exclude deep vein thrombosis, hypercoagulable state of blood and disseminated intravascular coagulation before enrollment;
* expected survival of more than 12 weeks as judged by the investigator;
* Be willing to attend study visits as required by the study protocol
* female patients of childbearing potential or male patients whose female partners are of childbearing potential must agree to use an effective method of contraception, such as a double-barrier method of contraception, condoms, oral or injectable contraceptives, and intrauterine devices (IUDs), for the duration of the study and within 30 days of the last study dose. Postmenopausal women (/>45 years of age and menopause of more than 1 year) and surgically sterilized women are exempt from this condition.

×

Критерии исключения

* have active central nervous system (CNS) leukemia;
* a known history of clinically significant liver disease, including viral or other hepatitis or cirrhosis:Positive hepatitis B surface antigen (HBsAg) serology requires a negative hepatitis B virus (HBV) DNA test for enrollment; For patients with hepatitis C virus (HCV) antibody serology positive, a negative HCV RNA test result is required for enrollment.
* known human immunodeficiency virus (HIV) infection;
* pregnant (positive screening pregnancy test) or lactating females;
* meet any of the following cardiac-related criteria:Hereditary long QT interval syndrome or QTcF /> 450 msec;Various clinically significant cardiovascular diseases, including acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting within 6 months prior to enrollment, congestive heart failure graded by the New York Heart Association (NYHA) as grade 2 or higher (inclusive);
* the patient has suffered from other malignant tumors within the past 5 years, except for radically treated basal cell carcinoma of the skin, carcinoma in situ of the breast or carcinoma in situ of the cervix;
* have received prior anti-leukemia therapy (for patients in Groups A and B), except for the following: use of hydroxyurea or leukocyte monocloning for control of white blood cell count, or treatment with all-trans retinoic acid due to initial suspicion of acute promyelocytic leukemia, or use of nondemethylating medications for the treatment of MDS
* for patients in Group C, prior anti-leukemia therapy, including chemotherapy, radiotherapy, hormonal therapy, targeted therapy, or immunotherapy, administered less than 2 weeks or 5 half-lives (whichever is shorter) prior to the start of study treatment; for patients who have undergone autologous hematopoietic stem cell transplantation or CAR-T therapy within 60 days prior to the start of study treatment, or have not recovered from toxicity associated with ASCT or CAR-T therapy Exclusion will be required for those who have had an allogeneic HSCT within 100 days prior to the start of study treatment, or if the patient still has a combination of active acute and chronic graft-versus-host disease, or if the patient still requires immunosuppressive therapy;
* pre-existing treatment with targeted menin (for Group A and B patients)
* pre-existing non-hematologic toxicities that have not returned to grade 0 or 1 (except alopecia areata);
* patients who have had a chest CT within 1 month prior to screening and suggestive of pulmonary nodules need to undergo T-SPOT (T-cell spotting test for tuberculosis infection) during the screening period, and those with positive results need to be excluded (no additional tests are required if no chest CT has been performed within 1 month prior to screening);
* uncontrolled active infection:Patients with non-serious infectious complications (e.g., oral Candida infection or uncomplicated urinary tract infection, etc.) for which oral/topical anti-infective therapy is being applied may be enrolled;Patients with severe infections requiring hospitalization or intravenous antibiotic therapy within 14 days prior to enrollment, patients with no evidence of infection, and patients receiving prophylactic anti-infective, antifungal, or antiviral therapy for prolonged neutropenia may be enrolled;Patients treated with intravenous antibiotics or hospitalized for febrile neutropenia, but no evidence of infectious etiology is found, and patients with a normal temperature for more than 72 hours without antipyretic medication may be enrolled;
* patients with known dysphagia, short bowel syndrome, gastroparesis, or other conditions that limit oral drug intake or gastrointestinal absorption;
* patients with a history of severe allergy to menin inhibitors or hypersensitivity to any component of BN104
* inadequate patient compliance with participation in this clinical study as judged by the investigator
* any other disease, metabolic abnormality, physical examination abnormality, or clinically significant laboratory test abnormality that, in the judgment of the investigator, gives reason to suspect that the patient has a disease or condition that is inappropriate for the use of the study medication, or that will interfere with the interpretation of the results of the study, or that places the patient at high risk.

NCT06456463 (добавлено: 2024-12-27)

A Study of Tagraxofusp in Combination With Venetoclax and Azacitidine in Adults With Untreated CD123+ Acute Myeloid Leukemia Who Cannot Undergo Intensive Chemotherapy

A Phase II Multicenter Open-label Trial of Tagraxofusp (Tag) in Combination With Venetoclax and Azacitidine (Ven/Aza) in Adults With Previously Untreated CD123+ Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy

Теги: #Newly diagnosed

Локации: AdventHealth Cancer Institute; Orlando; Florida; United States,Austin Hospital; Heidelberg; Victoria; Australia,Baylor Scott & White Health; Dallas; Texas; United States,Beth Israel Deaconess Medical Center; Boston; Massachusetts; United States,Box Hill Hospital; Box Hill; Victoria; Australia,Cleveland Clinic Foundation; Cleveland; Ohio; United States,Columbia University Irving Medical Center; New York; New York; United States,Concord Repatriation General Hospital; Concord; New South Wales; Australia,Dana Farber Cancer Institute (DFCI); Boston; Massachusetts; United States,Henry Ford Health; Detroit; Michigan; United States,Huntsman Cancer Institute; Salt Lake City; Utah; United States,John Theurer Cancer Center - Hackensack Meridian Health; Hackensack; New Jersey; United States,Massachusetts General Hospital; Boston; Massachusetts; United States,Monash Medical Centre; Clayton; Victoria; Australia,National Cancer Center; Goyang-si; Gyeonggi; Korea, Republic of,North Shore University Hospital; Manhasset; New Y

NCT06660368 (добавлено: 2024-12-20)

BCL2i CLAG-M in R/R Acute Myeloid Leukemia

A Prospective, Multicenter, Randomized, Open-Label, Phase II Study of Salvage BCL2i Plus CLAG-M in Relapsed or Refractory Acute Myeloid Leukemia

Теги: #Relapsed|Refractory

Локации: Dana-Farber Cancer Institute; Boston; Massachusetts; United States,Moffitt Cancer Center; Tampa; Florida; United States

NCT06741722 (добавлено: 2024-12-20)

Safety and Efficacy of Mitoxantrone Hydrochloride Liposome Based DCMG Regimen for R/R AML

Safety and Efficacy of Mitoxantrone Hydrochloride Liposome Based DCMG Regimen for Relapsed/refractory Acute Myeloid Leukemia

Теги: #Relapsed|Refractory

Локации: Chinese PLA General Hospital; Beijing; China

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Критерии исключения

* The subject`s prior anti-tumor treatment history meets one of the following conditions:
1. Previously received mitoxantrone or mitoxantrone hydrochloride liposome injection;
2. Previously received doxorubicin or other anthracyclines, with a total cumulative dose of doxorubicin /> 360 mg/m² (other anthracycline drugs are converted at a ratio of 1 mg doxorubicin equivalent to 2 mg daunorubicin or 0.5 mg idarubicin);
* Cardiac function and disease meet any of the following conditions:
1. Long QTc syndrome or QTc interval /> 480 ms;
2. Complete left bundle branch block, second-degree or third-degree atrioventricular block;
3. Severe, uncontrolled arrhythmia requiring medication;
4. New York Heart Association (NYHA) classification ≥ Class II;
5. Ejection fraction (EF) /< 50% or below the lower limit of normal for the study center`s laboratory;
6. History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmias, or any other arrhythmia requiring treatment, clinically significant pericardial disease, or evidence on electrocardiogram of acute ischemia or active conduction system abnormalities within 6 months prior to enrollment.
* Underwent any major surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, or experimental treatment within 2 weeks before the first administration of the study drug;
* Uncontrolled systemic diseases (such as progressive infections, uncontrolled hypertension, diabetes, etc.);
* Previous or current diagnosis of other malignancies (excluding adequately controlled basal cell carcinoma of the skin that is non-melanoma, breast/cervical carcinoma in situ, or other malignancies that have been adequately controlled without treatment in the past five years);
* Active hepatitis B or C infection during the viremic phase (Hepatitis B testing: if either HBsAg or core antibody is positive, add HBV-DNA testing; viral DNA levels exceeding 1x10/^3 copies/mL; Hepatitis C testing: if HCV antibody is positive, add HCV-RNA testing; viral RNA levels exceeding 1x10/^3 copies/mL);
* Human Immunodeficiency Virus (HIV) infection (HIV antibody positive);
* Pregnant women, breastfeeding women, patients who refuse to use effective contraception during the study period;
* Significant neurological or psychiatric history;
* Patients deemed unsuitable for participation in this study by the investigator.

NCT06737523 (добавлено: 2024-12-19)

Chiglitazar Sodium Combined With Venetoclax and Azacitidine (CVA) for the Treatment of R/R AML

A Multicenter, Prospective, Single-arm Clinical Study of Chiglitazar Sodium Combined With Venetoclax and Azacitidine (CVA) for the Treatment of Refractory/Relapsed Acute Myeloid Leukemia (R/R AML)

Теги: #Relapsed|Refractory

Локации: The First Affiliated Hospital of Xiamen University; Xiamen; Fujian; China

NCT06578247 (добавлено: 2024-12-06)

Quizartinib or Placebo Plus Chemotherapy in Newly Diagnosed Patients With FLT3-ITD Negative AML

Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial Of Quizartinib Administered in Combination With Induction and Consolidation Chemotherapy and Administered as Maintenance Therapy in Adult Patients With Newly Diagnosed FLT3-ITD Negative Acute Myeloid Leukemia

Теги: #FLT3 mutation , #Newly diagnosed

Локации: `Shathd` Ead Sofia; Sofia; Bulgaria,Affiliated Hospital of Nantong University; Nantong; China,Ajou University Hospital; Suwon; Korea, Republic of,Akademiska sjukhuset; Uppsala; Sweden,Asan Medical Center; Seoul; Korea, Republic of,Asst Dei Sette Laghi Ospedale Di Circolo E Fondazione Macchi Varese; Varese; Italy,Augusta University; Augusta; Georgia; United States,AZ DELTA; Roeselare; Belgium,Az Sint-Jan; Brugge; Belgium,Azienda Ospedaliera Universitaria Policlinico Tor Vergata; Rome; Italy,Azienda Ospedaliera Vincenzo Cervello; Palermo; Italy,Azienda Ospedaliero Universitaria Consorziale Policlinico Di Bari; Bari; Italy,Azienda Ospedaliero-Universitaria Cittă Della Salute E Della Scienza Di Torino; Torino; Italy,Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia (Presidio Spedali Civili); Brescia; Italy,Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda); Milano; Italy,Box Hill Hospital; Box Hill; Australia,Centre Hospitalier de Versailles; Le Chesnay Cede

NCT06709131 (добавлено: 2024-11-30)

A Clinical Study to Explore the Safety and Efficacy of CT0991 in Relapsed/Refractory Acute Myeloid Leukemia

A Clinical Study to Investigate the Safety and Efficacy of CT0991 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Теги: #Relapsed|Refractory

Локации: The first affiliated hospital of medical college of zhejiang university; Hangzhou; Zhejiang; China

×

Критерии исключения

1. The participant has any serious illness, laboratory abnormality, or psychiatric disorder that may impair the ability to receive or tolerate planned trial treatment; or the investigator judges that the participant `s participation in the clinical trial is not in his/her best interest (e.g., compromised health), or may hinder, limit, or confound protocol-specific assessments;
2. Participants were diagnosed with acute promyelocytic leukemia (APL), BCR-ABL positive leukemia (chronic myeloid leukemia in acute phase), secondary AML (other than MDS), central nervous system leukemia;
3. Participants with a history of epilepsy or other central nervous system disease;
4. Participants who have received autologous stem cell transplantation within 12 weeks or allogeneic stem cell transplantation within 6 months prior to screening;
5. Participant has clinically significant active GVHD or is receiving systemic corticosteroids for GVHD;
6. Participant has a second primary malignancy other than AML that has required treatment or has not been in complete remission within the past 2 years. The following cancers were considered curable, including nonmetastatic basal cell or squamous cell skin cancer, nonmetastatic prostate cancer, breast or cervical carcinoma in situ, and nonmuscle-invasive bladder cancer. Participants receiving ongoing hormonal therapy may be included in this trial at the discretion of the medical monitor in consultation with the investigator;
7. Participants had positive serology for human immunodeficiency virus (HIV) and syphilis, active hepatitis C virus (HCV) infection, or active hepatitis B virus (HBV) infection. Participants with a history of previously treated hepatitis B or C were allowed to be included in this trial if viral load could not be detected by qPCR and/or nucleic acid testing;
8. Major surgery within 14 days prior to washout or planned major surgery within 28 days after receiving CT0991 infusion. If required, the medical monitor and investigator must discuss to confirm whether the surgery is considered a major surgery before the participant is included in this trial;
9. Received anti-tumor therapy 14 days before Preconditioning, including chemotherapy, molecular targeted therapy;
10. Systemic therapeutic doses of glucocorticoids (defined as ≥ 20 mg prednisone or other equivalent per day) within 14 days prior to cleansing; however topical glucocorticoids such as topical dermal, eye drops, nasal sprays, inhalations, and physiologic replacement therapy doses of glucocorticoids are permitted ;
11. Vaccination with live attenuated vaccine or mRNA vaccine within 4 weeks prior to clear shower;
12. Allergic or intolerant to clear shower drugs and tocilizumab, or allergic to DMSO in cell infusion preparations, or previous history of other serious allergies such as anaphylactic shock;
13. Toxicities caused by previous treatment did not recover to Common Terminology Criteria for Adverse Events (CTCAE) ≤ Grade 1, except alopecia, peripheral neuropathy, and other events that were judged by the investigator to be unlikely to be cumulative toxicities due to clear shower or CT0991 infusion;
14. Pregnant or lactating women.

NCT06594445 (добавлено: 2024-11-23)

HM2023-05: GTB-3650 Trike for High Risk MDS and R/R AML

HM2023-05: GTB-3650 (Anti-CD16/IL-15/Anti-CD33) Tri-Specific Killer Engager (TriKE®) for the Treatment of High Risk Myelodysplastic Syndromes (MDS) and Refractory/Relapsed Acute Myeloid Leukemia (AML)

Теги: #Relapsed|Refractory

Локации: Masonic Cancer Center; Minneapolis; Minnesota; United States

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Критерии исключения

* Pregnant or breast-feeding. The effect of GTB-3650 TriKE on the fetus is unknown. Persons of childbearing potential must have a negative serum or urine test within 7 days prior to Cycle 1 Day 1 to rule out pregnancy.
* A candidate for hematopoietic stem cell transplant (HSCT) or newly relapsed after HSCT (e.g. no post-HSCT therapy given).
* Bi-phenotypic acute leukemia or mixed lineage leukemia.
* Acute promyelocytic leukemia (APL).
* New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan unless cleared for study by Pulmonary. Infiltrates attributed to infection must be stable/improving with associated clinical improvement after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
* Active systemic infection requiring parenteral antibiotic therapy. Any prior systemic infections must have resolved following optimal therapy.
* Known history of HIV.
* Active Hepatitis B or Hepatitis C (virus detectable by PCR) - chronic asymptomatic viral hepatitis is allowed.
* Positive test results from chronic hepatitis B infection (defined as positive HBsAg serology) and/or positive test results for hepatitis C (HCV antibody serology test).
* Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer currently in complete remission, or any other cancer from which the patient has been disease-free for 1 year
* Active central nervous system (CNS) malignancy or symptoms of CNS spread or administration of IT chemotherapy within 14 days prior to Day 1.
* Extramedullary disease causing symptoms and/or involving the CNS or spinal canal - asymptomatic extramedullary disease outside the CNS and spinal canal is eligible provided the marrow has measurable disease.
* Known autoimmune disease requiring active treatment or persons with a condition requiring systemic treatment with steroids (/> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before Cycle 1 Day 1. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
* The potential risk of QT/QTc prolongation is unknown in humans receiving
TriKE therefore either of the following is an exclusion criteria:
* QTc interval /> 480 msec at screening
* A family history of long QT syndrome
* Psychiatric illness/social situations that, in the judgement of the enrolling Investigator, would limit compliance with study requirements.
* Other illness or a medical issue that, in the judgement of the enrolling Investigator, would exclude the patient from participating in this study.

NCT06287944 (добавлено: 2024-11-22)

225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody With Fludarabine, Melphalan and Total Marrow and Lymphoid Irradiation as Conditioning Treatment for Donor Stem Cell Transplant in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome

Phase I Study of Escalating Doses of 225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody Added to the Conditioning Regimen of Fludarabine, Melphalan and Organ Sparing Total Marrow and Lymphoid Irradiation (TMLI) as Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: City of Hope Medical Center; Duarte; California; United States

×

Критерии включения

* Documented informed consent of the participant and/or legally authorized representative
* Assent, when appropriate, will be obtained per institutional guidelines
* ≥ 60 years. Note: Patients ≥ 18 years and /< 60 years with HCT-comorbidity index (CI) ≥ 2 are also included
* Karnofsky performance status ≥ 70
* Eligible patients will have a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories :
* Acute myelogenous leukemia:
* Patients with de novo or secondary disease in unfavorable risk group including poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for AML i.e., monosomal karyotype, -5,5q-,-7,7q-,11q23-non t(9;11), inv (3), t(3;3), t(6;9), t(9;22) and complex karyotypes (≥ 3 unrelated abnormalities), or all patient in intermediate risk groups accept patients with FLT3-NPM1+ disease, OR
* Patients with a complete morphological remission (CR) with minimal residual disease (MRD)-positive status by flow cytometry (≥ 0.1% by flow cytometry) or cytogenetic after at least 2 prior induction therapies, OR
* Patients with chemosensitive active disease defined as at least 50% reduction in their blast count after last treatment
* Myelodysplastic syndrome in high-intermediate (int-2) and high-risk categories per Revised International Prognostic Scoring System- (IPSS-R)
* Acute lymphocytic leukemia
* Patients with de novo or secondary disease according to NCCN guidelines for ALL hypoploidy (/< 44 chromosomes); t(v;11q23): MLL rearranged; t(9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomal abnormalities); high white blood cell (WBC) at diagnosis (≥ 30,000 for B lineage or ≥ 50,000 for T lineage); iAMP21loss of 13q, and abnormal 17p, OR
* Patients with a complete response (CR) with MRD-positive status by flow cytometry (≥ 0.1% by flow cytometry) or cytogenetics after at least 2 prior induction therapies, OR
* Patients with chemosensitive active disease defined as at least 50% reduction in their blast count after last treatment
* A pretreatment measured creatinine clearance (absolute value) of ≥ 60 ml/minute (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Patients must have a serum bilirubin ≤ 2.0 mg/dl (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Patients must have a serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 times the institutional upper limits of normal (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Patients must have a serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 times the institutional upper limits of normal (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Ejection fraction measured by echocardiogram or multigated acquisition scan (MUGA) ≥ 50% (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Diffusion capacity of the lung for carbon monoxide (DLCO) /> 50% predicted (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Forced expiratory volume in 1 second (FEV1) /> 50% predicted (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for /> 1 year (women only)
* DONOR SPECIFIC CRITERIA: All candidates for this study must have an human leukocyte antigen (HLA) (A, B, C, and DR) identical sibling who is willing to donate mobilized peripheral blood stem cells (preferred) or bone marrow, or have a 10/10 (A, B, C, DR and DQ) allele matched unrelated donor. DQ or DP mismatch is allowed per discretion of the principal investigator. City of Hope (COH) standards of practice (SOP) (B.001.11) will be used for allogeneic donor evaluation, selection, and consent. Donor screening will be in compliance with all requirements of Food and Drug Administration (FDA) regulation 21 CFR Part 1271 including donor screening for COVID-19 exposure or infection

×

Критерии исключения

* Patients who had a prior allogeneic transplant
* All patients with prior radiation treatment to the lung, liver, and kidney
* Patients who have received prior radiopharmaceutical therapy
* Inclusion of other patients with previous radiation exposure will be determined based on the radiation oncologist medical doctor (MD) principal investigator (PI) evaluation and judgement
* For patients with leukemia or MDS: Patients may not have received more than 3 prior regimens, where the regimen intent was to induce remission
* Receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous 2 weeks from conditioning
* Patients should have discontinued all previous intensive therapy, chemotherapy, or radiotherapy for 2 weeks prior to commencing therapy on this study. Note: Low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted. These include hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors (TKIs). FLT-3 inhibitors can also be given up to 3 days before conditioning regimen
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
* Patients with other active malignancies are ineligible for this study, other than non-melanoma skin cancers
* Patients should not have any uncontrolled illness including ongoing or active bacterial, viral or fungal infection
* The recipient has a medical problem or neurologic/psychiatric dysfunction which would impair his/her ability to be compliant with the medical regimen and to tolerate transplantation or would prolong hematologic recovery which in the opinion of the investigator (treating physician) would place the recipient at unacceptable risk
* Females only: Pregnant or breastfeeding
* Any other condition that would, in the Investigator`s judgment, contraindicate the patient`s participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

NCT06690827 (добавлено: 2024-11-16)

Clinical Trial of CD123-targeted CAR-NK Therapy for Relapse/refractory AML or BPDCN

Clinical Study of CD123 Targeting Chimeric Antigen Receptor NK Cells (CAR-NK) in the Treatment of Relapse/refractory Acute Myeloid Leukemia (AML)or Blastic Plasmacytoid Dendritic Cell Neoplasm(BPDCN)

Теги: #Relapsed|Refractory

Локации: Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology.; Wuhan; Hubei; China

NCT06679582 (добавлено: 2024-11-13)

Luveltamab Tazevibulin (STRO-002) in Infants and Children < 12 Years of Age with Relapsed/Refractory CBFA2T3::GLIS2 AML

A Phase 1/2, Open-label Study Evaluating the Efficacy, Safety, and Pharmacokinetics (PK) of Luveltamab Tazevibulin (STRO-002) in Infants and Children < 12 Years of Age with CBFA2T3::GLIS2 Acute Myeloid Leukemia (AML)

Теги: #Relapsed|Refractory

Локации: Children`s Hospital of Philadelphia (CHOP); Philadelphia; Pennsylvania; United States,Children`s Hospital of Philadelphia; Philadelphia; Pennsylvania; United States,Childrens Hospital of Alabama; Birmingham; Alabama; United States,Childrens National Hospital; Washington; District of Columbia; United States,VCU Massey Cancer Center-Adult Outpatient Pavillion; Richmond; Virginia; United States

NCT06643962 (добавлено: 2024-11-13)

Venetoclax Combined with Intensive Therapy for Acute Myeloid Leukemia Patients with Lower Early Peripheral Blast Clearance Rate After Standard Induction Therapy

A Single-Center Prospective Cohort Study to Evaluate the Efficacy and Safety of Intensifying Treatment with Venetoclax in Patients with Newly Diagnosed Acute Myeloid Leukemia (non-APL) and Exhibiting Lower Early Peripheral Blast Clearance Rate After Standard Intensive Induction Chemotherapy

Теги: #Newly diagnosed

Локации: Affiliated Hospital of Nantong University; Nantong; Jiangsu; China

NCT06370000 (добавлено: 2024-11-13)

Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality

REMAIN1: Relapse Prevention With Maintenance Oral Azacitidine in Transplant Eligible Patients With Acute Myeloid Leukemia Not Proceeding to Transplant Due to Racial or Socioeconomic Disparities

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: Virginia Commonwealth University; Richmond; Virginia; United States

×

Критерии включения

* Patients must have histologically or cytologically confirmed non-Acute Promyelocytic (APL) FLT3 negative AML and have completed induction and consolidation as defined by the treating physician and must be in complete response (CR), Complete response with partial hematologic recovery (CRh), or Complete response with incomplete count recovery (CRi) at time of study enrollment
* For patients in CR1, AML disease phenotype must be one that is considered for allo HCT in CR1 (intermediate or high risk by European Leukemia Net (ELN), MRD+ CR, slow clearance of MRD) or any AML phenotype (aside from FLT3+ and APL) in CR2 and beyond
* Medically eligible for allogeneic hematopoietic cell transplant (allo HCT) as defined by either: treating physician discretion, transplant physician discretion, or hematopoietic cell transplantation-specific Comorbidity index (HCT-CI) index of 5 or less
* Age ≥ 18 years
* Enrollment must occur within 4 months of completion of therapy
* A patient or staff identified health disparity in 1 of the 5 Centers for Disease Control (CDC) defined social determinants of health (SDOH). This may include financial difficulties, lack of caregiver support, difficulties with medical literacy, rurality, appropriate access to health care, lack of an appropriate allogeneic hematopoietic cell transplant (allo HCT) donor, substance abuse
* Patient must have adequate organ function defined as: Creatinine clearance (by Cockroft-Gault formula) greater than or equal to 29 mL/min, total bilirubin and aspartate aminotransferase/ alanine transaminase (AST/ALT) ≤ to institutional 2x upper limit of normal (except Gilbert`s syndrome, which may enroll if /< 2x patient`s baseline total bilirubin)
* Eastern Cooperative Oncology Group (ECOG) 0,1,2,3
* Ability to take oral medications
* No history of malabsorption syndrome which, in the investigator`s opinion, may inhibit absorption of oral medications
* Women of childbearing potential must consent to effective contraception during study treatment and at least 6 months following the last dose. Women who are breastfeeding are also excluded
* Male patients must consent to effective contraception during study and at least 3 months after last dose
* Ability to understand and the willingness to sign a written informed consent document

NCT06452732 (добавлено: 2024-11-09)

Using Multiparametric Flow Cytometry to Detect Peripheral Blood and Bone Marrow Leukaemia Stem Cells for Relapse Prediction in P-AML

Using Multiparametric Flow Cytometry to Detect Peripheral Blood and Bone Marrow Leukaemia Stem Cells for Relapse Prediction in Pediatric Acute Myeloid Leukaemia: a Prospective Study

Теги: #Relapsed|Refractory

Локации: Peking University People`s Hospital; Beijing; Beijing; China,People`s Hospital of Peking University; Beijing; Beijing; China

NCT06458257 (добавлено: 2024-11-08)

The Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Newly Diagnosed High-relapse-risk CEBPA Mutant Acute Myeloid Leukemia

The Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Newly Diagnosed High-relapse-risk CEBPA Mutant Acute Myeloid Leukemia

Теги: #Relapsed|Refractory

Локации: Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine; Shanghai; Shanghai; China

NCT06458244 (добавлено: 2024-11-08)

The Efficacy of Allo-HSCT in ND HR-CBF-AML

The Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Newly Diagnosed High-relapse-risk Core-binding-factor Acute Myeloid Leukemia

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine; Shanghai; Shanghai; China

NCT03816319 (добавлено: 2024-11-02)

TAK-243 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes With Increased Blasts

A Phase 1 Study of TAK-243 for Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes With Increased Blasts

Теги: #Relapsed|Refractory

Локации: Northwestern University; Chicago; Illinois; United States,University Health Network Princess Margaret Cancer Center LAO; Toronto; Ontario; Canada,Virginia Commonwealth University/Massey Cancer Center; Richmond; Virginia; United States

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Критерии включения

* Diagnosis of AML or MDS with increased blasts (MDS-IB) assessed by local laboratory review according to the 2022 World Health Organization (WHO) criteria for myeloid neoplasms. Both patients with MDS-IB1 (5-9% bone marrow blasts) and MDS-IB2 (10-19% bone marrow blasts) are eligible.
* Patients must have relapsed or refractory disease after receiving at least one prior line of therapy
* AML-specific inclusion criteria: Patients with relapsed or refractory AML with />= 5% bone marrow blasts after receiving at least two courses of intensive induction chemotherapy (including, but not limited to, 7+3 regimen, fludarabine, cytarabine, idarubicin and filgrastim /[FLAG-Ida/] and mitoxantrone, etoposide, and cytarabine /[MEC/]) or 2 cycles of venetoclax-based lower intensity regimen (azacitidine plus venetoclax or low-dose cytarabine plus venetoclax), and without any other approved therapies available that would be more appropriate in the investigator`s judgment. Patients who have received only one course of intensive induction chemotherapy but are not eligible for a second course because of decreased performance status or clear disease progression may be eligible for participation after discussion with the study principal investigator (PI). Patients with concomitant extramedullary disease relapse are eligible to participate, but not patients with isolated extramedullary relapse without bone marrow disease.
* MDS-specific inclusion criteria: Patients with relapsed or refractory MDS-IB with />= 5% bone marrow blasts after at least 4 cycles of hypomethylating agent (HMA)-based therapy or at least two courses of intensive induction chemotherapy and meet criteria for stable disease (SD), progressive disease (PD) or disease relapse according to the International Working Group 2023 response criteria for higher-risk MDS. Patients must not have access to any other approved therapies that would be more appropriate in the investigator`s judgment. Patients who have received less than 4 cycles of HMA-based therapy may be eligible to participate after discussion with the study PI if there is clear evidence of progression or intolerance to HMA-based therapy that precludes its continuation.
* Patients must have recovered from the effects of any prior systemic therapy, radiotherapy or surgery:
* Patients should not have received other investigational therapy within 2 weeks.
* Patients should not have received standard chemotherapy within 1 week of administration of study drug; hydroxyurea administration (for leukocyte count control) is permitted.
* Age />=18 years. Because no dosing or adverse event data are currently available on the use of TAK-243 in patients /<18 years of age, children are excluded from this study.
* Eastern Cooperative Oncology Group (ECOG) performance status =/< 2 (Karnofsky />= 50%).
* Serum bilirubin =/< 1.5 × institutional upper limit of normal (ULN).
* Patients with a known history of Gilbert`s syndrome may enroll.
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase /[SGOT/])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase /[SGPT/]) =/< 3 × institutional ULN.
* Serum creatinine /< 176 mcmol/L (2 mg/dL) OR
* Creatinine clearance /> 60 mL/min based on the Cockcroft-Gault equation.
* Documented normal cardiac function (/>= 50%) by echocardiogram or multi-gated acquisition (MUGA) scan.
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load withing 6 months are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* The effects of TAK-243 on the developing human fetus are unknown and ubiquitin-activating enzyme inhibitors are known to be teratogenic. For this reason, female patients must be:
* Postmenopausal (age-related amenorrhea />= 12 consecutive months or follicle-stimulating hormone /> 40 mIU/mL), for at least 1 year before the screening visit, OR
* Surgically sterile (i.e., who had undergone hysterectomy or bilateral oophorectomy), OR
If they are of childbearing potential:
* Agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence /[e.g., calendar, ovulation, symptothermal, postovulation methods/] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.) Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
* Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence /[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner/] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
* Patients should have a minimum life expectancy of 1 month.

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Критерии исключения

* Patients with acute promyelocytic leukemia (APL) or AML with t(15;17)(q22;q12) - PML::RARA).
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities /> grade 1), except anemia, neutropenia or thrombocytopenia of any grade and grade 2 peripheral neuropathy.
* Presence of any other malignancy requiring active therapy.
* Patients who are receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAK-243.
* Concomitant treatment with organic anion transport protein (OATP) and BCRP inhibitors or strong inducers/inhibitors of cytochrome P450 (CYP)3A4/5. Treatment with these agents must be discontinued at least 14 days prior to TAK-243 dosing. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
* Presence of an active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
* Presence of active graft-versus-host disease (GVHD) or continued treatment with systemic immunosuppressive agents following allogeneic hematopoietic stem cell transplantation (HSCT).
* Presence of any co-morbid condition that, in the opinion of the investigator, might compromise the patient`s safety, might interfere with participation in the trial or might interfere with the interpretation of trial results.
* Pregnant and lactating/breast-feeding women are excluded from this study because TAK-243 is a UAE-inhibiting agent with the potential for teratogenic or abortifacient effects and there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TAK-243. Females of child-bearing potential must have a negative serum pregnancy test within 7 days before enrollment and should not be lactating/breast-feeding. Breastfeeding should be discontinued if the mother is treated with TAK-243.
* Major surgery within 14 days before the first dose of any study drug or a scheduled surgery during study period.
* Patients with uncontrolled coagulopathy or bleeding disorder.
* Patients with known hepatic cirrhosis.
* Patients with known active cardiopulmonary disease defined as:
* Unstable angina withing 3 months prior to first dose of TAK-243;
* Myocardial infarction (MI) within 6 months prior to first dose of TAK-243 (patients who had MI and/or coronary revascularization more than 6 months before screening and who are without cardiac symptoms may enroll);
* Congestive heart failure (New York Heart Association /[NYHA/] Class III or IV;
* Cardiomyopathy with left ventricular ejection fraction (LVEF) /< 50%;
* Symptomatic pulmonary hypertension.
* Presence of active central nervous system (CNS) involvement (patients with prior CNS leukemia who have negative CNS cytology and who receive periodic prophylactic intrathecal chemotherapy are eligible).
* Patients with clinically significant arrhythmia:
* History of ventricular fibrillation or torsade de pointes at any time,
* Episode of grade />= 3 atrial fibrillation or flutter in the last 3 months, defined as symptomatic episode, requiring urgent intervention (cardioversion, pacemaker or ablation) or with life-threatening consequences.
* Uncontrolled high blood pressure (i.e., systolic blood pressure />180 mm Hg, diastolic blood pressure /> 95 mm Hg).
* Prolonged rate corrected QT (QTc) interval />= 480 msec, calculated using the Fridericia method.
* Patients with known severe or very severe chronic obstructive pulmonary disease (defined as forced expiratory volume in one second (FEV1) less than 30% or less than 50% of predicted), interstitial lung disease, or pulmonary fibrosis.
* Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).
* Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s).
* Patients with history of neutrophilic dermatosis (e.g. Sweet syndrome, pyoderma gangrenosum), relapsing polychondritis, polyarteritis nodosa and/or giant cell arteritis.
* Patients with VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome) or any other autoinflammatory disease.

NCT06377579 (добавлено: 2024-10-30)

OBServatory of Compassionate Use of IVOsidenib in France for Patients with Acute Myeloid Leukemia

OBServatory of Compassionate Use of IVOsidenib in France for Patients with Acute Myeloid Leukemia

Теги: #Relapsed|Refractory

Локации: Amiens CHU; Amiens; France,Angers CHU; Angers; France,Bayonne CH; Bayonne; France,Besançon CHU; Besançon; France,Bordeaux CHU; Pessac; France,CHU Estaing; Clermont-Ferrand; France,Créteil CHU HENRI MONDOR; Créteil; France,DUNKERQUE-Hôpital Alexandra Lepève; Dunkerque; France,Grenoble CHU; Grenoble; France,ICANS - Institut de cancérologie de strasbourg europe; Strasbourg; France,Le Mans CH; Le Mans; France,Lyon sud CHU; Lyon; France,Marseille IPC; Marseille; France,Meaux CH de l`Est francilien; Meaux; France,Montpellier - Chu Saint Eloi; Montpellier; France,Mulhouse Chu; Mulhouse; France,Nantes CHU; Nantes; France,Nice CHU; Nice; France,Orléans CHU; Orléans; France,Paris Saint Louis; Paris; France,Toulouse - IUCT Oncopole - Service d`Hématologie; Toulouse; France

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Описание

Mutations in IDH genes are found in numerous cancers and more specifically in acute myeloid leukemia (AML). These mutations target specific amino acids, at positions 140 or 172 of IDH2, and 132 of IDH1. Mutant IDH proteins acquire an abnormal enzymatic activity allowing them to convert α-ketoglutarate (αKG) into D-2 hydroxyglutarate (D-2HG), an oncometabolite which massively accumulates in IDH-mutated cells. At high levels, D-2HG behaves as a competitive inhibitor of αKG and affects the activity of Fe(II)/αKG-dependent dioxygenases. This enzymatic family is involved in a broad spectrum of pathways such as demethylation of histone (JHDM histone demethylases) or DNA (methylcytosine hydroxylases of the TET family). As a result, IDH-mutated cells show altered survival, motility, invasiveness and cell differentiation. In AML, IDH1 mutations might be present in 10-15% at diagnosis

Ivosidenib (IVO) a first-in-class, oral, irreversible inhibitor of mutant IDH1 has shown clinical activity as a single agent in studies involving patients with IDH1 mutated relapsed or refractory (R/R) AML and in front line settings. In phase II clinical trials, IVO yielded 30-35% of complete response rates both in frontline and R/R settings, with long lasting responses. Based on these results, the FDA (Food and Drug Agency) gave its approval for newly-diagnosed AML IDH1mut patients who are ≥ 75 years old or who have comorbidities and in R/R. However, European Medicines Agency (EMA)`s did not approved IVO due to lack of evidences to support the application. Agios Netherlands B.V. (the company that previously own the drug before Servier Laboratories) withdrew its EMA application. Nevertheless, IVO has been available in France through a compassionate use program (CUP), since February 2020 for R/R patients and March 2022 for first line treatment.

In this multicentric retrospective study, sponsor aim to evaluate the efficacy and safety of Ivo in two cohorts of IDH1mut AML patients treated within the CUP. The first cohort will concern patients treated in first line setting and the second cohort those treated in R/R disease. Results might provide new insights regarding IVO in real life settings and support signs of efficacy. This could provide new data for the haematologist community and for another appliance to grant EMA approval of IVO in the setting of R/R IDH1mut AML.

NCT06498973 (добавлено: 2024-10-30)

Tagraxofusp and Azacitidine for Maintenance Treatment in Patients With CD123 Positive AML and MDS Following Donor Hematopoietic Cell Transplant

CD123 Antibody Toxin Congregate (CD123 ATC; Tagraxofusp) Combined With Azacitidine for Maintenance Therapy Post Allogeneic Hematopoietic Cell Transplantation for Patients With CD123-Positive Malignant

Теги: #Relapsed|Refractory

Локации: City of Hope Medical Center; Duarte; California; United States

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Критерии включения

* Documented informed consent of the participant and/or legally authorized representative
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies.
* If unavailable, exceptions may be granted with study principal investigator (PI) approval
* Age: 18-75 years old
* Eastern Cooperative Oncology Group (ECOG) ≤ 2
* First or second allogeneic HCT-eligible patients with AML or MDS with high-risk cytogenetics per European LeukemiaNet (ELN) (AML) or Revised International Prognostic Scoring System (R-IPSS) (MDS); or by having active (morphological) or minimal residual disease (MRD)+ status at the time of HCT (by multicolor flowcytometry, cytogenetics or molecular testing) OR patients who underwent HCT for AML or MDS with high-risk cytogenetics per ELN (AML) or R-IPSS (MDS)
* Positive for CD123 by flow cytometry of either peripheral blood or bone marrow aspirates at the time of diagnosis at any time-point prior to HCT. (Note: CD123 measurement will be conducted using the 10-color Beckman Coulter Navios XL flow cytometer. We will use CD123 PE /[Beckman Coulter #A32535/] to gate the abnormal population of interest. This population will be compared to the internal negative control population /[e.g., T-cells/]. If more than 20% of the abnormal population is positive relative to this control, it will be classified as positive.)
* Any conditioning regiment or GVHD prophylaxis is allowed
* Any donor (i.e., match related/unrelated, mismatched, haploidentical, etc.) or graft source (i.e., bone marrow, mobilized peripheral blood stem cells, etc.) is allowed
* Prior treatment with CD123-therapy is allowed if no progression is documented on therapy
* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for /> 1 year (women only)
* STUDY MAINTENANCE TREATMENT: Complete response (CR) or MRD-positive on day 30 bone marrow biopsy (BMB) for disease assessment
* STUDY MAINTENANCE TREATMENT: Patients must be fully engrafted after HCT before starting the first cycle of maintenance. Full engraftment is defined as absolute neutrophil count (ANC) of 500 or above for 3 days and platelet count of more than 20,000 without transfusion for 7 consecutive days
* STUDY MAINTENANCE TREATMENT: ECOG ≤ 2
* STUDY MAINTENANCE TREATMENT: No treatment with anti-CD123 therapy after allogeneic HCT
* STUDY MAINTENANCE TREATMENT: No evidence of active or uncontrolled infection
* STUDY MAINTENANCE TREATMENT: No active GVHD; prednisone dose of ≤ 10 mg/daily is allowed
* STUDY MAINTENANCE TREATMENT: ANC ≥ 1.5 (within 7 days of day 1 of the cycle 1)
* NOTE: Transfusion (red blood cells /[RBC/] or platelet) to achieve the above-mentioned counts is allowed
* STUDY MAINTENANCE TREATMENT: Hemoglobin (HbG) ≥ 7 (within 7 days of day 1 of the cycle 1)
* NOTE: Transfusion (RBC or platelet) to achieve the above-mentioned counts is allowed
* STUDY MAINTENANCE TREATMENT: Platelet count ≥ 20K (within 7 days of day 1 of the cycle 1)
* NOTE: Transfusion (RBC or platelet) to achieve the above-mentioned counts is allowed
* STUDY MAINTENANCE TREATMENT: Total bilirubin ≤ 2 x upper limit of normal (ULN) (unless has Gilbert`s disease) (within 7 days of day 1 of the cycle 1)
* STUDY MAINTENANCE TREATMENT: Aspartate aminotransferase (AST) ≤ 2.5 x ULN (within 7 days of day 1 of the cycle 1)
* STUDY MAINTENANCE TREATMENT: Alanine aminotransferase (ALT) ≤ 2.5 x ULN (within 7 days of day 1 of the cycle 1)
* STUDY MAINTENANCE TREATMENT: Serum albumin /> 3.2 (within 7 days of day 1 of the cycle 1) (note that albumin infusions are not permitted in order to enable eligibility but can be given after treatment starts)
* STUDY MAINTENANCE TREATMENT: Creatinine clearance of ≥ 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 7 days of day 1 of the cycle 1)
* STUDY MAINTENANCE TREATMENT: If not receiving anticoagulants: International normalized ratio (INR) or prothrombin (PT) ≤ 1.5 x ULN (within 7 days of day 1 of the cycle 1)
* If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
* STUDY MAINTENANCE TREATMENT: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 7 days of day 1 of the cycle 1)
* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* STUDY MAINTENANCE TREATMENT: The Patient should agree to use acceptable contraceptive methods for the duration of the time in the study, and to continue to use contraceptive methods for 6 months following the end of study therapy
* STUDY MAINTENANCE TREATMENT: The patient may not have persistent clinically significant toxicities grade ≥ 1 from previous therapies, including cytotoxic chemotherapy, targeted therapies, biological therapies, or immunotherapies, not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue)
* STUDY MAINTENANCE TREATMENT: The patient has not received treatment with another investigational agent within 14 days of study entry
* STUDY MAINTENANCE TREATMENT: The patient does not have clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication)
* STUDY MAINTENANCE TREATMENT: The patient does not have uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study
* STUDY MAINTENANCE TREATMENT: The patient does not have known active or suspected central nervous system (CNS) disease. If suspected, CNS disease should be ruled out with relevant imaging and/or examination of cerebrospinal fluid
* STUDY MAINTENANCE TREATMENT: The patient does not have uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements
* STUDY MAINTENANCE TREATMENT: The patient does not have any condition which, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicities

NCT06514261 (добавлено: 2024-10-29)

Testing the Combination of an Anti-Cancer Drug, Iadademstat, With Other Anti-Cancer Drugs (Venetoclax and Azacitidine) for Treating AML

Phase 1 Trial of Iadademstat in Combination With Venetoclax and Azacitidine in Patients With Treatment Naive AML

Теги: #Relapsed|Refractory

Локации: UC Irvine Health/Chao Family Comprehensive Cancer Center; Orange; California; United States,UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care; Irvine; California; United States,University of Pittsburgh Cancer Institute (UPCI); Pittsburgh; Pennsylvania; United States,UPMC Hillman Cancer Center LAO; Pittsburgh; Pennsylvania; United States

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Критерии включения

* Patients must have established and confirmed diagnosis of intermediate or adverse-risk AML according to the European LeukemiaNet 2022 classification criteria
* Previously untreated AML excluding hydroxyurea and all-trans retinoic acid (ATRA). ATRA would only be used for suspected AML
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of iadademstat in combination with venetoclax and azacitidine in patients /< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
* Patient is able to swallow oral medications
* Patient must have a body weight of at least 50 kg due to the use of flat doses
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) OR direct bilirubin ≤ ULN for patients with total bilirubin levels /> 1.5 x ULN or ≤ 3 x ULN if patient has Gilbert`s disease
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase /[SGOT/])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase /[SGPT/]) ≤ 3 × institutional ULN or /< 5 ULN if due to AML
* Chronic kidney disease (CKD)-epidemiology collaboration (EPI) glomerular filtration rate (GFR) ≥ 40 mL/min/1.73 m/^2
* Peripheral white blood cell (WBC) count /< 25 x 10/^9/L on day 1 prior to treatment initiation. Hydroxyurea for up to 2 weeks is allowed for cytoreduction until 24 hours prior to study treatment
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better. Patients with a troponin leak (i.e. elevated troponin levels at presentation without evidence of an active myocardial infarction (MI) are eligible
* The effects of iadademstat on the developing human fetus are unknown. For this reason and because LSD1 inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, females of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 180 days after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Males with female partners of child-bearing potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 180 days after the last dose of study medication. Women of child-bearing potential agree not to donate or freeze egg(s) during the course of this study or within 180 days after receiving their last dose of study drug. Male patients agree not to donate sperm during the course of this study or within 180 days after receiving their last dose of study drug
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

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Критерии исключения

* Patients are willing and able to receive intensive induction chemotherapy
* Patients have isolated myeloid sarcoma or acute promyelocytic leukemia (APL) French-American-British (FAB) M3
* Patients who have not recovered from adverse events of grade 3 or more due to prior anti-cancer therapy (i.e., have residual toxicities /> grade 1) with the exception of alopecia
* Patients who are receiving any other investigational agents
* Patients who have active central nervous system (CNS) involvement by AML
* Patients who have disseminated intravascular coagulopathy with active systemic bleeding or venous or atrial signs of thrombosis
* Patients who require treatment while on study with concomitant drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline) except for drugs that are considered absolutely essential for the care of the patient and with appropriate treatment monitoring
* Patients with manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of oral drugs. In addition, patients with enteric stomata are also excluded
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to iadademstat, azacitidine, mannitol, or venetoclax
* Iadademstat Concomitant Medication Considerations: Patients are not allowed to receive prophylactic hematopoietic colony stimulating factors, any complementary or alternative medicine (any of various systems of healing or treating disease /[as non-prescription drugs, herbal medicine and homeopathy/])
* Patients should not use strong CYP3A inhibitors with the exception of antifungals for which standard of care (SOC) dose modifications of venetoclax exist
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous. This includes, but is not limited to:
* Myocardial infarction with evidence of residual abnormalities within 3 months prior to enrollment (Troponin leak alone not included if no residual dysfunction);
* New York Heart Association (NYHA) Class III or IV heart failure;
* Severe uncontrolled ventricular arrhythmias;
* Electrocardiographic evidence of acute ischemia or active life-threatening conduction system abnormalities:
* Since patients with AML frequently require supportive care with agents that affect the QTc, if clinically indicated, obtain an electrocardiogram (ECG) prior to enrollment
* As infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control (i.e., no signs of severe systemic inflammatory response that makes patient clinically unstable in the opinion of the investigator, and the patient is hemodynamically stable). Patients with uncontrolled infection shall not be enrolled until the infection is treated and brought under control
* Pregnant women are excluded from this study because iadademstat is LSD1 inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with iadademstat, breastfeeding should be discontinued if the mother is treated with iadademstat. These potential risks may also apply to other agents used in this study

NCT06651866 (добавлено: 2024-10-23)

Dose-escalation Study of D-CMG Regimen for the Treatment of Elderly Newly Diagnosed AML Patients

Dose Escalation Study of Liposomal Mitoxantrone Hydrochloride Injection Combined With Decitabine and Cytarabine (D-CMG) for the Treatment of Elderly Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

Теги: #Newly diagnosed

Локации: The First Affiliated Hospital of Xiamen University; Xiamen; Fujian; China

NCT06642025 (добавлено: 2024-10-16)

EX02 CAR-T Cells for Relapsed and Refractory Acute Myeloid Leukemia

An Open-label, Single-arm Clinical Study of EX02 CAR-T Therapy for Relapsed and Refractory Acute Myeloid Leukemia

Теги: #Relapsed|Refractory

Локации: The Second Affliated Hospital of Anhui Medical University; Hefei; Anhui; China

NCT06635681 (добавлено: 2024-10-15)

Efficacy of Venetoclax Combined with Intensive Chemotherapy in Different Subgroups of AML

Efficacy of Venetoclax Combined with Intensive Chemotherapy in Different Subgroups of Acute Myeloid Leukemia : a Multi-center, Single-arm Clinical Trial

Локации: Blood Diseases Hospital; Tianjin; Tianjin; China

NCT06626633 (добавлено: 2024-10-15)

2321GCCC: CRD3874-SI in Patients with Relapsed/refractory AML

Phase 1 Clinical Trial of the STING Agonist CRD3874-SI in Patients with Relapsed/refractory Acute Myeloid Leukemia

Теги: #Relapsed|Refractory

Локации: University of Maryland, Baltimore; Baltimore; Maryland; United States

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Критерии включения

* Male or female age ≥ 18 years at the time of signing the ICF
* Able to understand and willing to provide written informed consent
* Willing to comply with clinical study instructions and requirements.
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (Appendix 1).
* Pathologically confirmed diagnosis of AML by 2022 International Consensus Classification of Myeloid Neoplasms and Acute Leukemias criteria (2)
* AML may be de novo, following a prior hematologic disorder including myelodysplastic syndrome or Philadelphia chromosome-negative myeloproliferative neoplasm, and/or therapy-related
* Patients must have relapsed/refractory AML, with any prior therapies and any number of prior therapies, and have no further standard therapies available.
* Any prior therapy must have been completed ≥2 weeks prior to Day 1 of treatment on study, and all treatment-related adverse events (except alopecia) should have recovered to /<Grade 1.
* Hematologic abnormalities that are thought to be primarily related to leukemia are not considered to be toxicities and do not need to resolve to /<Grade 1.
* Myeloid growth factors must have been stopped ≥1 week (filgrastim) or ≥2 weeks (pegfilgrastim) before starting study treatment.
* Prior autologous hematopoietic stem cell transplantation is allowed.
* Prior allogeneic hematopoietic stem cell transplantation is also allowed, if patients are ≥60 days from stem cell infusion, have no evidence of graft-versus-host disease (GVHD) />Grade 1, and are />4 weeks off calcineurin therapy and ≥2 weeks off all immunosuppressive therapy.
* Peripheral blast count must be /<50 × 109/L. Hydroxyurea is permitted for blast count control before starting study treatment, but must be stopped ≥24 hours before starting study treatment. It may be reintroduced per physician decision if />50 × 109/L blasts recur during treatment Cycle 1 and managed per physician decision.
* Patients with other malignancies are allowed, if other malignancies are inactive and not requiring concurrent therapy except hormonal therapy for stable breast or prostate cancer.
* Aspartate aminotransferase (AST) must be /<2.5 x Upper Limit Normal (ULN), alanine aminotransferase (ALT) /<2.5 x ULN and total serum bilirubin /<1.5 x ULN unless thought due to hemolysis or Gilbert`s Syndrome.
* Adequate renal function as defined by calculated creatinine clearance (CrCl) />60 ml/minute by the Cockcroft-Gault formula
* Left ventricular ejection fraction (LVEF) />50%, as measured by echocardiogram (2D-ECHO)
* Life expectancy of at least three months at screening, according to the Investigator`s opinion
* Women of childbearing potential (defined as a sexually mature female who has not undergone a hysterectomy or bilateral oophorectomy or who has not been naturally postmenopausal for at least 24 consecutive months) must have a negative serum or urine pregnancy test within 7 days of study entry.
* Women of childbearing potential and sexually active men with female partners of childbearing potential must agree to use effective contraception, including abstinence or two forms of contraception, during study treatment and for four weeks after the last dose odf study drug.

×

Критерии исключения

* Acute promyelocytic leukemia
* Blast phase of chronic myeloid leukemia
* Known active central nervous system leukemia
* Concurrent chemotherapy, radiation therapy, immunotherapy or other investigational agents
* Active, uncontrolled infection
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the investigator`s judgment
* Malignancies other than AML requiring active therapy except hormonal therapy for stable breast or prostate cancer
* Active autoimmune disease other than vitiligo, type 1 diabetes, or controlled hypothyroidism
* Interstitial lung disease or any disease requiring supplemental oxygen, or history of pneumonitis or pulmonary fibrosis from any cause
* Known prior severe hypersensitivity to an investigational product or any component of the study drug therapy`s formulations including polyethylene glycol (PEG; National Cancer Institute Common Terminology Criteria for Adverse Events /[NCI CTCAE/] v5.0 Grade ≥ 3)
* Prior chemotherapy or targeted small molecule therapy within 3 weeks, anticancer monoclonal antibody within four weeks or five half-lives, if shorter, or radiation therapy within 2 weeks prior to the first CRD3874-SI infusion prior to study Day 1, or not recovered (i.e., Grade ≤ 1 or at baseline) from AE due to a previously administered agent (Note: Alopecia is acceptable. If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy)
* Prior organ transplantation, other than allogeneic or autologous hematopoietic stem cell transplantation.
* Currently participating in a study and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is longer.
* Received a live vaccine within 30 days of the planned start of study drug. (Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed.)
* Evidence of clinically significant immunosuppression including the following:
* Primary immunodeficiency state such as SCID
* Concurrent opportunistic infection
* Receiving systemic immunosuppressive therapy (/>2 weeks) including oral steroid doses /> 10 mg/day of prednisone or equivalent within seven days prior to enrollment. In the setting of non-immune mediated indications for use, chronic/active low dose steroid use (equivalent to ≤ 10 mg/day prednisone) may be permitted at the discretion of the Principal Investigator (Note: Other steroid formulations or steroid use for other indications may be permitted and include: 1) Intranasal, inhaled, ocular, or topical steroids, or local steroid injection (e.g., intra-articular injection); 2) Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; 3) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
* History or evidence of symptomatic autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other), or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past two years prior to enrollment (Note: Replacement therapy /[e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency/] is not considered a form of systemic treatment for autoimmune disease.)
* Evidence of clinically significant interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis related to prior immunotherapy treatment
* Uncontrolled medical condition including current active infection requiring systemic therapy or symptomatic congestive heart failure (CHF) within six months that in the Investigator`s opinion compromises the ability of the participant to complete all study-related requirements safely
* Mean resting corrected QTcF interval ≥ 470 ms on a 12-lead electrocardiogram (ECG) for males and females
* History of unstable or deteriorating cardiovascular disease within the previous six months prior to screening, including but not limited to the following:
* Unstable angina or myocardial infarction (MI)
* Cerebrovascular accident (CVA)/stroke
* CHF (New York Heart Association /[NYHA/] Class III or IV)
* Uncontrolled clinically significant arrhythmias
* Known to be positive for active Hepatitis B (HBV; Hepatitis B surface antigen /[HBsAg/] reactive with detectable HBV DNA), or Hepatitis C (HCV; detectable HCV RNA /[qualitative/])
* Patients with chronic HBV (positive HBsAg and/or Hepatitis B core antibody /[HBcAb/] and negative HBV DNA by polymerase chain reaction /[PCR/]) are eligible for this study if they are on suppressive antiviral therapy and deemed safe by a gastroenterologist
* Patients who are HCV antibody (Ab)-positive but HCV RNA-negative due to prior treatment or natural resolution will be considered eligible
* Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) disease that is not controlled. Individuals known to be HIV-positive will be considered eligible if all the following criteria are met:
* Established antiretroviral treatment (ART) for at least four weeks and have an HIV viral load less than 400 copies/mL prior to enrollment
* CD4+ T-cell counts ≥ 350 cells/uL
* No opportunistic infection within the past 12 months
* No known history of active tuberculosis (TB)
* The presence of a concurrent active malignancy that in the opinion of the Investigator could compromise the conduct of the study or interfere with determining the outcomes of the study objectives
* Women who are pregnant or breastfeeding
* Expecting to conceive or father children within the projected duration of the study, starting with the prescreening or screening visit through three months after the last dose of study treatment(s)

NCT06508489 (добавлено: 2024-10-15)

A Study to Investigate Natural Killer Cell Engager (SAR443579) With Different Agents in Participants With Hematological Malignancies

A Phase 1/Phase 2, Randomized, Open-label, Multi Cohort, Multi Center, Study Assessing the Safety, Tolerability and Preliminary Efficacy of SAR443579 a Natural Killer Cell Engager (NKCE) Targeting CD123, Administered With Different Agents in Participants With CD123 Expressing Hematological Malignancies

Теги: #Newly diagnosed

Локации: City of Hope National Medical Center- Site Number : 8400003; Duarte; California; United States,City of Hope Site Number : 8400003; Duarte; California; United States,Investigational Site Number : 0360001; Melbourne; Victoria; Australia,Investigational Site Number : 0360002; Wollongong; New South Wales; Australia,The Ohio State University Wexner Medical Center - Ohio State Outpatient Care Upper Arlington- Site Number : 8400001; Columbus; Ohio; United States,The University of Texas MD Anderson Cancer Center- Site Number : 8400008; Houston; Texas; United States

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Критерии исключения

* Any clinically significant, uncontrolled medical conditions (including any serious active systemic infection that is not controlled)
* Known second malignancy either progressing or requiring active treatment within the last 3 years prior to first IMP administration
* Known acquired immunodeficiency syndrome (AIDS-related illnesses) or HIV disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or SARS-CoV-2 infection. With exception for:
1. HBV as determined by positive test for hepatitis B surface antigen (HBsAg) and/or HBV DNA. Participant who tests positive for anti-hepatitis B core (HBc) antigen IgG (with or without testing positive for anti-HBs), but tests negative for HBsAg and HBV DNA, is eligible.
2. A participant who tests positive for anti-HCV antibodies and has undetectable HCV RNA without receiving antiviral treatment for HCV is eligible.
* Active, known, or suspected clinically significant autoimmune disease that has required systemic treatment in the past 2 years prior to first IMP administration, except controlled by replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)
* Predicted life expectancy ≤3 months.
* Medical conditions requiring treatment with medications with narrow therapeutic index that are substrates of CYP enzymes and that cannot be closely monitored to allow for dose adjustment.
* Ongoing adverse event of NCI CTCAE /[Version 5.0/] Grade 2 or greater severity cause by any prior anti-cancer therapy
Substudy 01:
* Patient with Acute Promyelocytic Leukemia (APL)
* Known active central nervous system involvement with AML at the time of enrollment as evidenced by cytology or pathology
* Cardiovascular disease of New York Heart Association (NYHA) Class ≥2.
* Malabsorption syndrome or other condition that precludes enteral route of administration
* A baseline QTc interval of (using the Fridericia correction calculation) />470 msec.
* Subject has received treatment with at least one of the following:
1. A hypomethylating agent, venetoclax and/or chemo therapeutic agent for AML other than hydroxyurea used for disease control prior to the initiation of study therapy.
2. Experimental therapies for AML.
3. Concomitant medications of strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
The above information is not intended to contain all considerations relevant to a participant`s potential participation in a clinical trial.

NCT06511882 (добавлено: 2024-10-15)

Discontinuation of Hypomethylating Agent and Venetoclax in Patients With AML MRD

Discontinuation of Hypomethylating Agent and Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) Who Have Achieved Negative Measurable Residual Disease (MRD)

Теги: #Newly diagnosed

Локации: Moffitt Cancer Center; Tampa; Florida; United States

NCT06492707 (добавлено: 2024-10-15)

DR-18 for the Treatment of Relapsed or Persistent Acute Myeloid Leukemia or Myelodysplastic Syndrome After Hematopoietic Cell Transplantation, the DR. DREAM Trial

Decoy-Resistant Interleukin-18 (DR-18) for Relapse or Pre-emptive Treatment of Measurable Residual Disease After Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndrome (DR. DREAM)

Теги: #Relapsed|Refractory

Локации: Fred Hutch/University of Washington Cancer Consortium; Seattle; Washington; United States

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Критерии исключения

* Active moderate-severe thrombotic microangiopathy (TMA) as evidenced by any of the following: /> 10 schistocytes per high-power field, or required anti-C5 or other anti-complement therapy for TMA in the prior 4 weeks, any of the following manifestations if attributed to TMA in the prior 4 weeks: hypertension, worsening or new renal insufficiency, ≥ 2+ proteinuria, hematochezia, seizure, transient or ongoing neurologic deficits
* Renal insufficiency: Estimated glomerular filtration rate (eGFR) (calculated per the performing laboratory`s standard formula) or measured 24 hour (hr.) creatinine clearance /< 30 mL/min
* Hemodialysis in the prior 4 weeks
* Major cardiac event requiring evaluation in the emergency room (ER) or hospitalization in the past 4 weeks
* New York Heart Association (NYHA) class II or higher congestive heart failure (CHF) in the past 4 weeks
* Uncontrolled cardiac arrhythmias, including atrial fibrillation
* Left ventricular ejection fraction (LVEF) /< 35%. LVEF may be established with echocardiogram or MUGA scan, and left ejection fraction must be ≥ 35%
* Liver dysfunction: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) /> 5 x upper limit of normal (ULN) or bilirubin /> 3 x ULN
* Active uncontrolled infection. NB: Examples of controlled infections:
* Bacterial infection may be still requiring antibiotics at the time of enrollment, but clinical signs and symptoms of the infection should be improving. If the subject had bloodstream infection, negative blood cultures off antibiotics must be documented prior to initiating DR-18 treatment. For urinary tract infection, a repeat urine culture must be sterile prior to initiating DR-18. Radiographic improvement of bacterial pneumonia may lag behind clinical improvement so is not mandatory prior to DR-18 initiation
* Fungal infection may be still requiring antifungal medication at the time of enrollment, but evidence of clinical response to antifungal medication (such as regression of lesions on chest CT) must be available at the time of enrollment
* Asymptomatic shedding of respiratory viruses after cessation of antiviral therapy, or if not specifically treated with antiviral therapy, is permitted
* Cytomegalovirus (CMV) viremia or organ infection meeting institutional criteria for CMV treatment with antiviral therapy such as ganciclovir, valganciclovir or foscarnet must be on maintenance phase of treatment or must have completed treatment and must not be in the induction treatment phase at the time of enrollment. Low-level CMV viremia not meeting institutional criteria for antiviral therapy is permitted, including low-level viremia in patients receiving CMV prophylaxis with letermovir
* Any of the following: Pulmonary dysfunction requiring supplemental oxygen, even intermittently, in the past 2 weeks; corrected diffusion capacity of the lung for carbon monoxide (DLCO) or forced expiratory volume in 1 second (FEV1) /< 60% predicted; bronchiolitis obliterans syndrome; prior diagnosis of idiopathic pulmonary fibrosis; prior diagnosis of drug-induced pneumonitis; cryptogenic organizing pneumonia under active treatment
* Seizure in the past 4 weeks or significant underlying neurologic disease: Study participants must not have significant active underlying neurologic disease, such as Parkinson`s disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, prior symptomatic ischemic or hemorrhagic stroke, or transient ischemic attack, unless approved by principal investigator (PI). Peripheral neuropathy related to diabetes or prior chemotherapy is acceptable
* Other medical, social, or psychiatric factor that interferes with medical appropriateness and/or ability to comply with study, as determined by the PI
* Known allergic reactions to any of the components of study treatments
* Concurrent use of other investigational anti-cancer agents
* Peripheral blood T cell chimerism /< 40%

NCT06492304 (добавлено: 2024-10-15)

A Safety and Efficacy Study Evaluating CTX131 in Adult Subjects With Relapsed/Refractory Hematologic Malignancies

A Phase 1/2 Dose Evaluation and Cohort Expansion Study of the Safety and Efficacy of Anti-CD70 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX131) in Adult Subjects With Relapsed/Refractory Hematologic Malignancies

Теги: #Relapsed|Refractory

Локации: Research 2; Stanford; California; United States,Research Site 1; Houston; Texas; United States,Research Site 2; Bronx; New York; United States,Research Site 3; Boston; Massachusetts; United States,Research Site 4; New York; New York; United States,Research Site 5; Bronx; New York; United States,Research Site 5; Stanford; California; United States,Research Site 6; Phoenix; Arizona; United States

NCT06529250 (добавлено: 2024-10-15)

Intermediate-dose HAD Regimen for CEBPA Double-mutated AML

A Multicenter, Randomized, Controlled Clinical Trial of Intermediate-dose HAD Regimen for CEBPA Double-mutated Acute Myeloid Leukemia

Локации: Blood Hospital; Tianjin; Tianjin; China

NCT06529731 (добавлено: 2024-10-15)

Interferon-γ (IFN-γ) With Donor Leukocyte Infusion to Treat Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes Post Allogeneic Hematopoietic Stem Cell Transplantation

A Phase 2 Trial of Interferon-γ (IFN-γ) in Combination With Donor Leukocyte Infusion (DLI) to Treat Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) After Allogeneic Hematopoietic Stem Cell Transplantation (alloSCT)

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: UPMC Hillman Cancer Center; Pittsburgh; Pennsylvania; United States

NCT06543381 (добавлено: 2024-10-15)

Olutasidenib for the Treatment of Patients with IDH1 Mutated AML, MDS or CMML After Donor Hematopoietic Cell Transplant

Pilot Trial of Olutasidenib Maintenance Post Allogeneic Hematopoietic Cell Transplantation in Patients Carrying IDH1 Mutation with AML, MDS, or CMML Disease

Теги: #Relapsed|Refractory

Локации: City of Hope Medical Center; Duarte; California; United States,Cleveland Clinic Cancer Center; Cleveland; Ohio; United States

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Критерии включения

* Documented informed consent of the participant and/or legally authorized representative
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval
* Age: ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) ≤ 2 or Karnofsky performance status (KPS) ≥ 70
* Patients who are scheduled to receive or have already undergone allogeneic hematopoietic cell transplantation (alloHCT) from any donor type, any conditioning regimen, and regardless of GVHD prophylaxis will be include
* Patients must have AML, MDS, or CMML with mIDH1 diagnosis at diagnosis (regardless of time from HCT). Note: Patient with pre-HCT disease relapse will no be included if mIDH1 is not detected after relapse
* Day 30 marrow post alloHCT should show evidence of morphologic remission with /< 5% bone marrow (BM) blasts. Patients with MRD-positive status either by flow cytometry or IDH1 mutation testing will be eligible
* Patients with previous therapy with IDH1 inhibitors will be included
* Absolute neutrophil count (ANC) /> 1000/mm/^3 (within 28 days prior to day 1 of protocol)
* Hemoglobin ≥ 8.0 gm/dL (within 28 days prior to day 1 of protocol)
* Platelets ≥ 50,000/mm/^3 (within 28 days prior to day 1 of protocol) Note: Patients with lower counts can enroll if infection cytomegalovirus (CMV)/human herpes virus 6 (HHV6), etc. is being treated actively
* Bilirubin ≤ 2 x upper limit of normal (ULN) (within 28 days prior to day 1 of protocol) (unless has Gilbert`s disease). Patients with abnormal liver function tests (LFTs) due to active GVHD will not be eligible
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase /[SGOT/])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase /[SGPT/]) ≤ 2 x ULN (within 28 days prior to day 1 of protocol). Patients with abnormal LFTs due to active GVHD will not be eligible
* Creatinine clearance of ≥ 30/min/1.73 m/^2 for participants with creatinine levels above institutional normal per 24 hour urine test or the Cockcroft-Gault formula (within 28 days prior to day 1 of protocol)
* Corrected QT interval (QTc) ≤ 480 ms (Note: To be performed within 28 days prior to day 1 of protocol therapy)
* Seronegative for HIV antigen/antibody (Ag/Ab) combo, hepatitis C virus (HCV) (if positive, hepatitis C ribonucleic acid /[RNA/] quantitation must be performed), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin /[RPR/]) (within 28 days prior to day 1 of protocol)
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 28 days prior to day 1 of protocol). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Agreement by females and males of childbearing potential, defined as not being surgically sterilized (men and women) or have not been free from menses for /> 1 year (women only), to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy

NCT06549790 (добавлено: 2024-10-15)

Study of NMS-03597812 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia

A Phase Ia/Ib Study of NMS-03597812 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia Including Patients With TP53 Mutations

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: Blood and Marrow Transplant Group of Georgia; Atlanta; Georgia; United States,City of Hope - Duarte; Duarte; California; United States,Gabrail Cancer Research Center; Canton; Ohio; United States,The University of Texas MD Anderson Cancer Center; Houston; Texas; United States

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Критерии включения

* Confirmed diagnosis of refractory/relapsed (R/R) AML according to 2022 ELN recommendation:
Phase Ia
* single agent dose escalation of NMS-03597812: R/R AML patients who have exhausted standard therapy: a) prior fit patients to intensive chemotherapy (IC): failed at least one cycle of IC in front-line therapy or b) prior unfit to IC: failed at least 2 cycles of hypomethylating agents (HMA)/venetoclax combination therapy, or at least 4 cycles of HMA monotherapy; c) patients must have failed all other approved therapies for which they are eligible, including FLT3 inhibitors, IDH1/2 inhibitors, and CD33 directed therapy
Phase Ib
* Cohort A: single agent in R/R AML TP53mt patients who have exhausted standard therapy: a) prior unfit to intensive chemotherapy (IC): failed at least 2 cycles of HMA/venetoclax combination therapy, or at least 4 cycles of HMA monotherapy; b) patients must have failed all other approved therapies for which they are eligible, including FLT3 inhibitors, IDH1/2 inhibitors, and CD33 directed therapy
* Cohort B: single agent in R/R AML TP53wt patients who have exhausted standard therapy: a) prior fit patients to intensive chemotherapy (IC): failed at least one cycle of IC in front-line therapy or b) prior unfit to IC: failed at least 2 cycles of HMA/venetoclax combination therapy, or at least 4 cycles of HMA monotherapy; c) patients must have failed all other approved therapies for which they are eligible, including FLT3 inhibitors, IDH1/2 inhibitors, and CD33 directed therapy
* Adult (age ≥ 18 years) patients
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Unless agreed with sponsor, the interval from prior antitumor treatment should be at least 2 weeks or 5 half-lives, whichever is longer, other than hydroxyurea
* All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTCAE version 5.0 Grade≤ 1
* Adequate organ function
* Must use highly effective contraception or true abstinence. Female patients must be surgically sterile or, if patient is of childbearing potential, must agree to use effective contraception of therapy and in the following 210 days after discontinuation of study treatment. Since NMS-03597812 has potential induction of CYP3A4, women of childbearing potential must be advised that hormonal contraceptives might lose efficacy and must use alternate form of highly effective contraception. Male patients must be surgically sterile or must agree to use highly effective contraception or true abstinence during the period of therapy and in the following 120 days for male patients who must refrain from donating sperm during this period after discontinuation of study treatment.
* Capability to swallow capsules intact (without chewing, crushing, or opening)
* Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study indications or procedures
* Signed and dated Independent Ethics Committee (IEC) or Institutional Review Board (IRB)-approved informed consent form indicating that the patient is aware of the neoplastic nature of his/her disease and has been informed of the procedures to be followed, the investigational nature of the therapy, potential benefits, side effects, discomforts, risks, and alternative treatments.

×

Критерии исключения

* Current enrollment in another interventional clinical study unless only participating in survival follow up
* White blood cells (WBC) count />20×10/^3/microliter (μL). However, patients can be treated with hydroxyurea and/or leukapheresis prior to study treatment start to reduce the WBC to ≤ 20×10/^3/μL to enable eligibility for study drug dosing.
* Diagnosis of acute promyelocytic leukemia or BCR-ABL-positive leukemia
* Currently active second malignancy, except for adequately treated basal or squamous cell skin cancer and/or cone biopsied in situ carcinoma of the cervix uteri and/or superficial bladder cancer.
* Patients with known leukemia involvement of central nervous system (CNS).
* Hematopoietic stem cell transplantation (HSCT) within 3 months of treatment start and/or persistent non- hematologic toxicities of Grade ≥2 related to the transplant
* Active acute or chronic graft versus host disease (GVHD) requiring immunosuppressive treatment
* Patients with QTcF interval ≥ 470 milliseconds or with risk factors for torsade de pointes (e.g., uncontrolled heart failure, uncontrolled hypokalemia, history of prolonged QTc interval or family history of long QT syndrome). For patients receiving treatment with concomitant medications known to prolong the QTc interval, replacement with another treatment needs to be considered. If replacement or discontinuation is not clinically feasible, a careful risk/benefit evaluation should be performed prior to enrollment.
* Pregnancy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the screening period prior to start of study drug.
* Breast-feeding or planning to breast feed during the study or within 90 days after study treatment.
* Known active gastrointestinal disease (eg, gastro-duodenal ulcer, gastrectomy, Crohn`s disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
* Patient who are receiving concomitant medications with antacids (proton pump inhibitors are strictly prohibited; calcium carbonate antacids are only allowed 6 hours prior to a dose or 1 hour after). Note: exclusion criterion not applicable to optional backfill cohort for investigation of drug-drug interaction with antiacids.
* Patient who are receiving concomitant medications that are strong inducers or inhibitors of CYP3A4 (with the exception of azole antifungals) and CYP2C9 that cannot be replaced with alternative therapy.
* Patients who are receiving concomitant medications that are sensitive substrates of CYP3A4,CYP2D6, CYP1A2 and CYP2B6 with narrow therapeutic window that cannot be replaced with alternative therapy. Drugs with broad therapeutic indices may still be acceptable.
* Patients who are receiving concomitant medications that are strong or moderate P-gp inhibitors that cannot be replaced with alternative therapy.
* Major surgery within 4 weeks before study treatment start.
* Radiotherapy within 4 weeks before study treatment start. However, if the radiation portal covered ≤5 % of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy.
* History of necrotic pancreatitis or acute severe pancreatitis, requiring medical intervention and/or hospitalization, in the previous 6 months before study treatment start.
NOTE: Other protocol defined inclusion/exclusion criteria may apply.

NCT06439199 (добавлено: 2024-10-15)

Biological, Prospective Study Evaluating the Dosage of Plasma Cytokines Including the FLT3 Ligand and IL6 of Patients Treated With Non-intensive Chemotherapy

Single-center, Biological, Uncontrolled, Prospective Study Evaluating the Dosage of Plasma Cytokines Including the FLT3 (FMS-like Tyrosine Kinase 3) Ligand and IL6 With a View to Making a First Estimate of Their Prognostic Value on the Outcome of Patients Treated With Non-intensive Chemotherapy Such as Azacytidine for Acute Myelogenous Leukemia (AML), High Risk Myelodysplastic Syndrome (HR-MDS) or Chronic Myelomonocytic Leukemia (CMML)

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: Nantes University Hospital; Nantes; Loire-Atlantique; France

NCT06401603 (добавлено: 2024-10-15)

A Phase I Study of Decitabine, Lisaftoclax, and Olverembatinib in Patients With Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia

A Phase I Study of Decitabine, Lisaftoclax, and Olverembatinib in Patients With Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia

Теги: #Relapsed|Refractory

Локации: MD Anderson Cancer Center; Houston; Texas; United States

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Критерии включения

a) Diagnosis: Age ≥18 years with CML-AP, CML-MBP, or Ph+ AML by WHO 2016 criteria.
* Participants must have been intolerant or resistant to at least one prior BCR::ABL1 TKI
2. Performance status ≤3 (ECOG Scale).
3. Adequate liver, cardiac, renal and pancreatic function as defined by the following criteria:
1. Total serum bilirubin /< 1.5 x upper limit of normal (ULN), unless due to Gilbert`s syndrome, hemolysis or the underlying leukemia approved by the PI
2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) /< 3 x ULN, unless due to the underlying leukemia approved by the PI
3. Creatinine clearance ≥30 mL/min
4. Serum amylase or lipase /< 1.5 x ULN
4. Ability to understand and the willingness to sign a written informed consent document
5. Willingness to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months after completion of study participation. For women of child-bearing potential, adequate methods of contraception include: complete abstinence,, hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal Ligation or hysterectomy, subject/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide.
Exclusion Criteria:
1. Participants who have previously received lisaftoclax or olverembatinib
2. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
3. Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
4. Clinically significant and uncontrolled cardiovascular disease, including but not restricted to:
i. Myocardial infarction (MI), stroke, revascularization, unstable angina, or transient ischemic attack within 6 months.
ii. Left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment.
iii. Diagnosed or suspected congenital long QT syndrome. iv. Clinically significant atrial or ventricular arrhythmias (such as uncontrolled, clinically significant atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) as determined by the treating physician.
v. Prolonged QTc interval on pre-entry electrocardiogram (/> 480 msec) unless corrected after electrolyte replacement.
vi. History of venous thromboembolism including deep venous thrombosis or pulmonary embolism within the past 3 months, excluding line associated DVT of the upper extremity vii. Uncontrolled hypertension (diastolic blood pressure />100mmHg; systolic />150mmHg).
5. Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment).
6. Active central nervous system leukemia
7. Known human immunodeficiency virus (HIV) seropositive, unless well-controlled on stable doses of anti-retroviral therapy.
8. Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection Note: Participants who have isolated positive hepatitis B core antibody (ie, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Participants who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
9. Participants with a prior or concurrent malignancy whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the PI
10. Consumed strong inducer of CYP3A or p-glycoprotein within 14 days of study enrollment, or 5 half-lives, whichever is longer. Agents include but are not limited to: carbamazepine, phenytoin, rifampin, and St. John`s wart
11. Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator. Prior recent treatment with corticosteroids, hydroxyurea, cytarabine (up to 2 g/m2 given for cytoreduction within the preceding 7 days) and/or an FDA-approved BCR::ABL1 TKI is permitted.
12. Inability to swallow
13. Pregnant or breastfeeding women will not be eligible
14. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Decitabine, Lisaftoclax, and Olverembatinib or other agents used in study.
15. Participants with psychiatric illness/social situations that would limit compliance with study requirements.

NCT06399640 (добавлено: 2024-10-15)

Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia

Phase Ib Study of Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia

Теги: #Relapsed|Refractory

Локации: Vanderbilt University/Ingram Cancer Center; Nashville; Tennessee; United States

NCT06398457 (добавлено: 2024-10-15)

Darzalex Faspro (Daratumumab and Hyaluronidase-fihj) Before Standard Desensitization and Allogeneic Peripheral Blood Stem Cell Transplantation in Adult Patients at High-risk for Primary Graft Failure Secondary to Donor Specific Antibodies

A Pilot Study of Darzalex Faspro (Daratumumab and Hyaluronidase-fihj) Before Standard Desensitization and Allogeneic Peripheral Blood Stem Cell Transplantation in Adult Patients at High-risk for Primary Graft Failure Secondary to Donor Specific Antibodies

Теги: #Plasma cell leukemia , #Relapsed|Refractory

Локации: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Baltimore; Maryland; United States

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Критерии исключения

1. Previous exposure to Daratumumab-SC or other anti-CD38 therapy
1. Exposure to Daratumumab-SC or other anti-CD38 therapies (unless a re-treatment study)
2. Exposure to an investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic half-lives, whichever is longer.
3. Focal radiation therapy within 14 days prior to beginning of planned RIC allogeneic peripheral blood stem cell transplant regimen with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma
2. Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) /< 50% of predicted normal. Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is /< 50% of predicted normal.
3. Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
4. Known hypersensitivity or intolerance to boron or mannitol, sorbitol, corticosteroids, monoclonal antibodies or human proteins, or the excipients
5. Diagnosis of multiple myeloma or Amyloid light-chain (AL) amyloidosis
6. A planned myeloablative alloBMT or the planned use of bone marrow or cord blood as a stem cell source
7. History of HIV infection at any time in past.
8. Seropositive for hepatitis B (HBV) (defined by a positive test for hepatitis B surface antigen /[HBsAg/] positive, or antibodies to hepatitis B surface and/or core antigens /[antiHBs or antiHBc, respectively/] with hepatitis B virus /[HBV/]- DNA quantitation positive). Patients who are positive for antiHBs and/or antiHBc must have a negative polymerase chain reaction (PCR) for HBV-DNA quantitation result during screening. Patients with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR. Those who are PCR positive will be excluded.
9. Seropositive for hepatitis C (except in the setting of a sustained virologic response (SVR), defined as aviremia at least 12 weeks after completion of antiviral therapy)
10. Clinically significant cardiac disease, including:
1. Myocardial infarction within 6 months before RIC alloHSCT or unstable or uncontrolled disease/condition related to or affection cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV)
2. Uncontrolled cardiac arrhythmia

NCT06386302 (добавлено: 2024-10-15)

Chidamide, Venetoclax, and Azacitidine for Newly Diagnosed Acute Myeloid Leukemia

A Multicenter, Randomized, Controlled Clinical Trial of Chidamide Combined With Venetoclax and Azacitidine in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) Who Are Not Suitable for Intensive Chemotherapy

Теги: #Newly diagnosed

Локации: Blood Hospital; Tianjin; Tianjin; China

NCT06284486 (добавлено: 2024-10-15)

A Multi-Site Break Through Cancer Trial: Phase II Study Investigating Dual Inhibition of BCL2 and Menin in AML MRD Using the Combination of Venetoclax and Revumenib

A Multi-Site Break Through Cancer Trial: Phase II Study Investigating Dual Inhibition of BCL2 and Menin in AML MRD Using the Combination of Venetoclax and Revumenib

Теги: #Relapsed|Refractory

Локации: MD Anderson Cancer Center; Houston; Texas; United States

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Критерии исключения

1. Prior treatment with a menin inhibitor.
2. Participants who are expected to receive standard therapy (either intensive or hypomethylating agent and venetoclax) with continued tolerability and benefit.
3. Participants who are expected to be able to proceed with stem cell transplantation within the next 30 days.
4. Participants with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment.
5. The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea for patients with rapidly proliferative disease or for control of counts during differentiation syndrome. (3) use of steroids for treatment of differentiation syndrome.
6. Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
7. Participants with a concurrent active malignancy under treatment.
8. Known active hepatitis B (HBV) or Hepatitis C (HCV) or HIV infection.
9. Female subjects who are pregnant or breast-feeding.
10. Participant has an active uncontrolled infection.
11. Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
12. QTc />450 msec for males and QTc />470 msec for females using the Fridericia Formula.
13. History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator`s opinion might confound the results of the study, interfere with the participants`s participation for the full duration of the study, or is not in the best interest of the patient to participate.
14. Clinically active central nervous system (CNS) leukemia.
15. Participants on immunosuppressive therapy post-HSCT at the time of screening (must be off all systemic immunosuppression therapy for at least 2 weeks and calcineurin inhibitors for at least 4 weeks). The use of topical steroids for cutaneous graft-versus-host disease (GVHD) or stable systemic steroid doses less than or equal to 20 mg of prednisone daily are permitted.
16. Participants with Grade /> 2 active acute GVHD, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.

NCT06247787 (добавлено: 2024-10-15)

A Study to Find the Highest Dose of Imetelstat in Combination With Fludarabine and Cytarabine for Patients With AML, MDS or JMML That Has Come Back or Does Not Respond to Therapy

A Phase 1 Study of GRN163L (Imetelstat) in Combination With Fludarabine and Cytarabine for Patients With Acute Myeloid Leukemia That is in Second or Greater Relapse or That is Refractory to Relapse Therapy; Myelodysplastic Syndrome or Juvenile Myelomonocytic Leukemia in First or Greater Relapse or is Refractory to Relapse Therapy

Теги: #Relapsed|Refractory

Локации: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center; Houston; Texas; United States,C S Mott Children`s Hospital; Ann Arbor; Michigan; United States,Children`s Hospital Colorado; Aurora; Colorado; United States,Children`s Hospital of Alabama; Birmingham; Alabama; United States,Children`s Hospital of Orange County; Orange; California; United States,Children`s Hospital of Philadelphia; Philadelphia; Pennsylvania; United States,Children`s Hospital of Pittsburgh of UPMC; Pittsburgh; Pennsylvania; United States,Cincinnati Children`s Hospital Medical Center; Cincinnati; Ohio; United States,Riley Hospital for Children; Indianapolis; Indiana; United States,Saint Jude Children`s Research Hospital; Memphis; Tennessee; United States,UCSF Medical Center-Mission Bay; San Francisco; California; United States,University of Minnesota/Masonic Cancer Center; Minneapolis; Minnesota; United States,Washington University School of Medicine; Saint Louis; Missouri; United States

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Критерии включения

* Patients must be ≥ 1 year and ≤ 18 years of age at the time of study enrollment
* Patients, with or without down syndrome (DS), and with de novo acute myeloid leukemia, therapy-related AML, MDS or JMML and meet one of the following:
* Second or greater relapse or refractory AML, including isolated extramedullary disease (EMD), but excluding isolated central nervous system (CNS) or isolated testicular relapse
* First or greater relapse of MDS
* First or greater relapse of JMML
* For flow cytometry, it`s strongly recommended to enroll onto APAL2020SC or to send samples to Hematologics, Inc. Otherwise, assessments must be performed at a College of American Pathologists (CAP)/Clinical Laboratory Improvement Act (CLIA) certified lab that has expertise in AML.
* For FISH/Karyotype, samples must be sent to a Children`s Oncology Group (COG)-approved Cytogenetics Lab
* Bone marrow relapse AML:(patients must meet one of the following criteria to be defined as having relapsed disease)
* A single bone marrow sample showing ≥ 5% leukemic blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing, or other molecular method
* A single bone marrow with at least two tests showing ≥ 1% leukemic blasts; examples of tests include:
* Flow cytometry showing ≥ 1% leukemic blasts by multidimensional flow cytometry (MDF)
* Karyotypic abnormality with at least one metaphase similar or identical to diagnosis
* Fluorescence in situ hybridization (FISH) abnormality identical to one present at diagnosis
* Polymerase chain reaction (PCR) or next generation sequencing (NGS)-based demonstration of leukemogenic lesion identical to diagnosis and ≥ 1%
* In cases where a bone marrow aspirate cannot be obtained because of extensive fibrosis, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy. A complete blood count documenting the presence of at least 1,000/ uL (i.e., a white blood cell /[WBC/] count ≥ 10,000/uL with ≥ 10% blasts or a WBC count of ≥ 5,000/uL with ≥ 20% blasts) circulating leukemic cells (blasts) can also be used if a bone marrow aspirate or biopsy cannot be performed
* Extramedullary relapse: Biopsy proven extramedullary disease after documented complete remission
* Refractory disease AML: Following a re-induction cycle after a second relapse, or refractory to two reinduction attempts after first relapse with:
* A single bone marrow sample showing ≥5% leukemic blasts by flow cytometry, FISH testing, or other molecular method
* A single bone marrow with at least two tests showing ≥1% leukemic blasts: examples of tests include:
* Flow cytometry showing ≥1% leukemic blasts by multidimensional flow cytometry (MDF)
* Karyotypic abnormality with at least one metaphase similar or identical to diagnosis.
* FISH abnormality identical to one present at diagnosis
* Polymerase chain reaction (PCR) or next generation sequencing (NGS)-based demonstration of leukemogenic lesion identical to diagnosis and ≥ 1%
* In cases where a bone marrow aspirate cannot be obtained because of extensive fibrosis, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy. A complete blood count documenting the presence of at least 1,000/ uL (i.e., a WBC count ≥ 10,000/uL with ≥ 10% blasts or a WBC count of ≥ 5,000/uL with ≥ 20% blasts) circulating leukemic cells (blasts) can also be used if a bone marrow aspirate or biopsy cannot be performed
* Extramedullary refractory disease:
* Biopsy proven persistent extramedullary disease
* In cases where a bone marrow aspirate cannot be obtained because of extensive fibrosis, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy. A complete blood count documenting the presence of at least 1,000/ µL (i.e., a WBC count ≥ 10,000/μL with ≥ 10% blasts or a WBC count of ≥ 5,000/μL with ≥ 20% blasts) circulating leukemic cells (blasts) can also be used if a bone marrow aspirate or biopsy cannot be performed
* Central nervous system disease: Patients with relapsed or refractory disease with central nervous system (CNS) 1 and CNS 2 status are eligible
* MDS: Bone marrow relapse:(patients must meet one of the following criteria to be defined as having relapsed disease)
* A single bone marrow sample showing ≥ 5% leukemic blasts by flow cytometry, FISH testing, or other molecular method
* A single bone marrow with at least two tests showing ≥1% leukemic blasts; examples of tests include:
* Flow cytometry showing ≥ 1% leukemic blasts by multidimensional flow cytometry (MDF)
* Karyotypic abnormality with at least one metaphase similar or identical to diagnosis
* FISH abnormality identical to one present at diagnosis
* Polymerase chain reaction (PCR) or next generation sequencing (NGS)-based demonstration of MDS associated lesion identical to diagnosis and ≥ 1%
* In cases where a bone marrow aspirate cannot be obtained because of extensive fibrosis, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
* JMML: Diagnosis: Patients must have had histologic verification of juvenile myelomonocytic leukemia (JMML) at original diagnosis and currently have relapsed or refractory disease. The diagnosis is made based on the following criteria
* JMML category 1 (all of the following):
* Splenomegaly
* /> 1000 (1x10/^9 /uL) circulating monocytes
* /< 20% Blasts in the bone marrow or peripheral blood
* Absence of the t(9;22) or BCR/ABL fusion gene
* The diagnostic criteria must include all features in category 1 andeither (i) one of the features in category 2 or (ii) two features from category 3 to make the diagnosis
* JMML category 2 (at least one of the following if at least two category 3 criteria are not present):
* Somatic mutation in RAS or PTPN11
* Clinical diagnosis of NF1 or NF1 gene mutation
* Homozygous mutation in CBL
* Monosomy 7
* JMML category 3 (at least two of the following if no category 2 criteria are met):
* Circulating myeloid precursors
* White blood cell count, />10 000 (10x10/^9 / uL)
* Increased hemoglobin F for age
* Clonal cytogenetic abnormality
* Granulocyte-macrophage-colony-stimulating factor {GM-CSF) hypersensitivity
* Patients with relapsed JMML must have had at least one cycle of intensive frontline therapy or at least 2 cycles of a deoxyribonucleic acid (DNA) hypomethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality. Frontline therapy is defined as one cycle of intravenous chemotherapy that includes of any of the following agents: fludarabine, cytarabine, or any anthracycline but specifically excludes oral 6-mercaptopurine. Frontline therapy will also include any conditioning regimen as part of a stem cell transplant. Patients who transform to AML at any point with more than 20% blasts are eligible for this trial per the AML specific criteria
* Patient`s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky (≥ 50) for patients /> 16 years of age and Lansky for patients ≤ 16 years of age (≥ 50)
* Patients must have fully recovered (grade /< 2) from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required time frame, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See DVLhomepage on the COG Members site for commercial and investigational agent classifications (https://cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/TableOfMyelosuppressiveAnti-CancerAgents.pdf). For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
* ≥ 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy
* Note: Cytoreduction with hydroxyurea must be discontinued ≥ 24 hours prior to the start of protocol therapy
* Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil (ANC) counts):
* ≥ 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research Ccoordinator prior to enrollment
* Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1
* Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon, or cytokines (other than hematopoetic growth factors)
* Stem cell Infusions (with or without total body irradiation /[TBI/]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: ≥ 84 days after infusion and no evidence of graft-versus-host disease GVHD
* Patients must be off calcineurin inhibitors for at least 28 days prior to the date of enrollment. Patients may be on physiological doses of steroids (equivalent to ≤ 10 mg prednisone daily for patients ≥ 18 years or ≤ 10mg/m/^2/day /[up to a maximum of 10 mg/day/] for patients /< 18 years)
* Autologous stem cell infusion including boost infusion: ≥ 30 days
* Cellular Therapy: ≥ 30 days after the completion of any type of cellular therapy (eg, modified T cells, NK cells, dendritic cells, etc.)
* External Beam Radiation (XRT)/external beam irradiation including protons: ≥ 14 days after local XRT; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis; ≥ 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (eg, radiolabeled antibody, 131I MIBG): ≥ 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to imetelstat
* For patients with leukemia:
* Platelet count ≥ 25,000/uL (may receive platelet transfusions). These patients must not be known to be refractory to red cell or platelet transfusion
* Hemoglobin />= 8.0 g/dL at baseline (may receive red blood cell (RBC) transfusions)
* Adequate renal function defined as:
* Estimated glomerular filtration rate (GFR) (eGFR) ≥ 70 mL/min/1.73 m/^2 "Bedside" Schwartz formula (2009): eGFR = 0.413 x (height /[cm/] / serum creatinine /[mg/dL/]) OR
* a 24 hour urine creatinine clearance ≥ 70 mL/min/1.73 m/^2 OR
* a GFR ≥ 70 mL/min/1.73 m/^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Adequate liver function defined as:
* Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
* Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase /[ALT/]) ≤ 3 x ULN, unless attributed to leukemia involvement
* AST ≤ 3 x ULN, unless attributed to leukemia involvement
* Albumin ≥ 2 g/dL
* Shortening fraction of ≥ 27% by echocardiogram, or
* Ejection fraction of ≥ 50% by gated radionuclide study

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Критерии исключения

* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, or because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (eg, male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. Women of childbearing potential must use highly effective contraception in addition to a barrier method during treatment and for at least 1 month after the last dose of imetelstat or longer if required by the institutional guidelines for conventional chemotherapy (fludarabine/cytarabine). Male patients who can father a child should use contraception during treatment and for 3 months after the last dose of imetelstat or longer if required by the institutional guidelines for conventional chemotherapy (fludarabine/cytarabine). Imetelstat should not be administered to nursing mothers
* Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid
* Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
* Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy
* Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Specific to MDS patients: Low-grade MDS/refractory cytopenia of childhood (RCC) - MDS with less than 2% blasts in peripheral blood (PB) or less than 5% blasts in the bone marrow (BM) by morphology
* Uncontrolled seizure disorder that is not stabilized with anti-convulsants
* Patient has undergone surgery that requires general anesthesia within 3 weeks before enrollment (line placement/removal/revision or tissue collection is allowed)
* Known hypersensitivity to the study drug or excipients of the preparation
* Patients with acute promyelocytic leukemia (APL) with PML-RARA genetic abnormality according to World Health Organization (WHO) classification or t(15;17) are not eligible
* Patients known to have a congenital bone marrow failure syndrome where increased risk of toxicity may be expected as judged by the Investigator, for example dyskeratosis congenita, are not eligible
* Patients with isolated or refractory CNS or isolated or refractory testicular relapse are not eligible
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

NCT06138990 (добавлено: 2024-10-15)

Pharmacoscopy-guided Clinical Standard-of-care in R/r AML

Pharmacoscopy-guided Clinical Standard-of-care in Relapsed/refractory Acute Myeloid Leukemia, a Randomized Phase-2 Clinical Trial

Теги: #Relapsed|Refractory

Локации: Inselspital Bern; Bern; Switzerland,University Hospital Zurich; Zurich; Switzerland

NCT05554393 (добавлено: 2024-10-15)

Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial)

A Measurable Residual Disease (MRD) Driven, Phase II Study of Venetoclax Plus Chemotherapy for Newly Diagnosed Younger Patients With Intermediate Risk Acute Myeloid Leukemia: A Tier 1 MYELOMATCH Clinical Trial

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: Baptist Cancer Center-Grenada; Grenada; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Collierville; Collierville; Tennessee; United States,Baptist Memorial Hospital and Cancer Center-Desoto; Southhaven; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Golden Triangle; Columbus; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Memphis; Memphis; Tennessee; United States,Baptist Memorial Hospital and Cancer Center-Oxford; Oxford; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Union County; New Albany; Mississippi; United States,Benefis Sletten Cancer Institute; Great Falls; Montana; United States,Billings Clinic Cancer Center; Billings; Montana; United States,Bozeman Health Deaconess Hospital; Bozeman; Montana; United States,Cancer Care Center of O`Fallon; O`Fallon; Illinois; United States,Cancer Care Specialists of Illinois - Decatur; Decatur; Illinois; United States,Cancer Hematology Centers - Flint; Flint; Michigan; U

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Критерии включения

* Patient must have enrolled onto MYELOMATCH and must have been given a treatment assignment to MyeloMATCH to MM1YA-CTG01 based on the presence of an actionable mutation as defined in MYELOMATCH
* Participants must have been registered to master screening and re-assessment protocol (myeloMATCH MSRP) prior to consenting to this study. Participants must have been assigned to this clinical trial, via MATCHBox, prior to registration to this study. Participants must have agreed to have specimens submitted for translational medicine (MRD) and must be offered the opportunity to submit biosamples for banking for future research as per the myeloMATCH MSRP
* Note: Pre-enrollment/diagnosis labs must have already been performed under the MSRP
* Previously untreated, de novo acute myeloid leukemia (AML) defined by /> 20% myeloblasts in the peripheral blood or bone marrow (refer to the 2016 updated World Health Organization /[WHO/] classification of myeloid neoplasms and acute leukemia) excluding all the following categories of AML:
* Favorable cytogenetics: (t(8;21)q22;q22.1); RUNX1-RUNX1T1, inversion 16(p13.1;q22), t(16;16)(p13.1;q22); CBFB-MYH11
* CEBPA biallelic mutations
* NPM1 mutation
* AML with PML-RARalpha
* AML with any adverse cytogenetics, TP53 mutation, RUNX1 mutation, ASXL1, 11q23/KMT2 rearrangements
* AML with FLT3-ITD or FLT3-TKD mutations
* Therapy related AML, or AML following a diagnosis of myelodysplasia or myeloproliferative neoplasm Participants with central nervous system (CNS) disease are eligible for this trial and will be treated according to institutional guidelines with intrathecal chemotherapy for this aspect of their disease
* Age 18-59 years at time of induction therapy
* Eastern Cooperative Oncology Group (ECOG) performance status =/< 3
* Total bilirubin =/< 2 x institutional upper limit of normal (ULN) (must be done within 7 days of enrollment)
* Aspartate aminotransferase (AST) (serum glutamate pyruvate transaminase /[SGPT/]) +/or alanine aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase /[SGOT/]) =/< 3 × institutional ULN (must be done within 7 days of enrollment)
* Cardiac ejection fraction />= 50% (echocardiography or multigated acquisition scan /[MUGA/]) (must be done within 7 days of enrollment)
* Calculated creatinine clearance />= 30 mL/min/ 1.73m/^2; Clearance to be calculated using Cockcroft formula (must be done within 7 days of enrollment)
* White blood cells (WBC) must be /< 25 x 10/^9/L. Hydroxyurea and leukapheresis are permitted to control the WBC prior to enrollment and initiation of protocol-defined therapy but must be stopped at least 24 hours prior to the initiation of protocol therapy
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Women/men of childbearing potential must have agreed to use a highly effective contraceptive method while on treatment and for 6 months after stopping study drug. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures.
Women of childbearing potential will have a pregnancy test to determine eligibility as part of the pre-study evaluation; this may include an ultrasound to rule-out pregnancy if a false-positive is suspected. Patient will be considered eligible if an ultrasound is negative for pregnancy
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
* Patients must be accessible for treatment, response assessment and follow up. Patients enrolled on this trial must be treated and followed at the participating centre. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
Patients must agree to return to their primary care facility for any adverse events which may occur through the course of the trial
* In accordance with Canadian Cancer Trials Group (CCTG) policy, protocol treatment is to begin within 7 working days of patient enrollment
* Participants receiving strong or moderate CYP3A inhibitors must agree to discontinue use at least 48 hours prior to start of study treatment if assigned to arm 1 or 2
* Patients with known human immunodeficiency virus (HIV) infection who are on effective anti-retroviral therapy and have undetectable viral load within 6 months of enrollment are eligible for this trial
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days of enrollment. Patients need to be on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection who have been treated and cured are eligible. Patients who with active HCV infection who are currently being treated must have an undetectable HCV viral load within 28 days of enrollment to be eligible

NCT06317649 (добавлено: 2024-06-21)

Venetoclax and HMA Treatment of Older and Unfit Adults With FLT3 Mutated Acute Myeloid Leukemia (AML) (A MyeloMATCH Treatment Trial)

A Randomized Phase II Study of Venetoclax and HMA-Based Therapies for the Treatment of Older and Unfit Adults With Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia (AML): A MyeloMATCH Treatment Trial

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: Augusta University Medical Center; Augusta; Georgia; United States,Baptist Cancer Center-Grenada; Grenada; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Collierville; Collierville; Tennessee; United States,Baptist Memorial Hospital and Cancer Center-Desoto; Southhaven; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Golden Triangle; Columbus; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Memphis; Memphis; Tennessee; United States,Baptist Memorial Hospital and Cancer Center-Oxford; Oxford; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Union County; New Albany; Mississippi; United States,Benefis Sletten Cancer Institute; Great Falls; Montana; United States,Billings Clinic Cancer Center; Billings; Montana; United States,Bozeman Health Deaconess Hospital; Bozeman; Montana; United States,Cancer Care Center of O`Fallon; O`Fallon; Illinois; United States,Cancer Care Specialists of Illinois - Decatur; Decatur; Illinois;

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Критерии включения

* Patient must be ≥ 60 years of age or adults ˂ 60 who in the opinion of the treating physician are better served by azanucleoside-based therapy rather than intensive, cytarabine-based induction based on clinical status (i.e., performance status, age /> 75 years), organ dysfunction, or disease biology
* Patient must have a morphologically confirmed diagnosis of AML according to the World Health Organization (WHO) 2016 classification excluding acute promyelocytic leukemia (APL) with PML-RARA, AML with RUNX1-RUNX1T1, or AML with CBFB-MYH11
* Patient must have no prior therapy for AML with the exception of hydroxyurea and all-trans retinoic acid (ATRA), or leukapheresis. Patients with cytarabine-based emergency therapy prior to the start of therapy on this trial are eligible
* Patient must have no prior therapy with hypomethylating agents or FLT3 inhibitors
* Patient must have the FLT3-ITD or D835 mutation based on MyeloMATCH Master Screening and Reassessment Protocol (MSRP)
* Patient must be assigned to this protocol by the myeloMATCH MSRP
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
* All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
* A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Contraception measures must continue for 30 days after the last dose of venetoclax for all patients and for 6 months after the last dose of gilteritinib for patients of childbearing potential and for 4 months after the last dose of gilteritinib for male patients with partners of childbearing potential. Patient must not breastfeed during treatment and for 2 months after treatment ends
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Total bilirubin 2X ≤ institutional upper limit of normal (ULN) (unless thought to be elevated due to disease involvement or Gilbert`s syndrome)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase /[SGOT/])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase /[SGPT/]) =/< 3.0 x institutional ULN
* Either measured or estimated by Cockcroft-Gault equation
* Creatinine clearance of ≥ 30 mL/min/1.73m/^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration/randomization are eligible for this trial
* Patients must not have a baseline corrected QT interval ≥ 480 msec using Fredericia correction (QTcF).
NOTE: Since older patients are at risk for prolonged QTc and many will require supportive care with agents that affect the QTc, an ECG is recommended if clinically indicated. If the QTc is prolonged, they should be treated on tier advancement process (TAP) instead of EA02
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patient must not have the medical necessity for ongoing treatment with a strong CYP3A4 inducing drug
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patients must not have an active or uncontrolled infection

NCT06357182 (добавлено: 2024-06-13)

Iadademstat in Combination With Azacitidine and Venetoclax in Treating Newly Diagnosed Acute Myeloid Leukemia

A Phase Ib Investigation of the LSD1 Inhibitor Iadademstat (ORY-1001) in Combination With Azacitidine and Venetoclax in Newly Diagnosed AML

Теги: #Relapsed|Refractory

Локации: OHSU Knight Cancer Institute, Portland, Oregon, United States,OHSU Knight Cancer Institute; Portland; Oregon; United States

×

Критерии исключения

* Prior allergic response to iadademstat (IADA), venetoclax, azacitidine, or any excipients in the formulations
* Body weight /< 50 kg
* Investigational therapy within 5 half-lives or, if unknown, within 28 days prior to start of IADA
* Treatment for AML within 14 days prior to start of IADA. Cytoreduction for patients with proliferative disease must meet the criteria listed in inclusion criteria
* Radiotherapy less than 14 days prior to start of IADA
* Recent and significant medical interventions, such as major surgery within 28 days prior to the start of IADA, or stem cell transplant within 100 days prior to the start of IADA. Patients with active treatment for graft-versus-host disease (GVHD) are excluded
* Another active malignancy within 5 years prior to the start of IADA, or at the investigator`s discretion
* Treatments targeting or inhibiting LSD1/KDM1A or BCL 2 within 12 months prior to the start of IADA
* Documented dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
* Treatment with monoamine oxidase inhibitors (e.g., tranylcypromine), if treatment is not finalized at least 3 weeks prior to the start of IADA
* Active central nervous system involvement with AML
* Uncontrolled infection. Participants with controlled infection must be afebrile and hemodynamically stable for at least 72 hours prior to start of IADA and must be amenable to alternate treatment if current treatment will interact with investigational regimen
* Active hepatic disorder or documented positive hepatitis B or C virus (HBV/HCV, respectively) status, except in cases of undetectable HBV/HCV viral load for at least 3 months prior to the start of IADA. (Hepatitis B or C testing is not required for eligibility assessment.)
* Individuals serology positive for human immunodeficiency virus (HIV) and under active treatment with highly active antiretroviral therapy (HAART) (or another therapy that may interfere with metabolism of study agents). Otherwise, enrollment may be considered in cases of HIV that is controlled with another treatment type or in cases that that acceptable modification of the patient`s HIV treatment exists
* Use a P-gp inhibitor within 23 days prior to treatment with venetoclax
* Use of strong or moderate CYP3A4 inducers or inhibitors within 2 days or 3 half lives whichever is longer, prior to start of treatment with venetoclax
* Unwillingness to stop breastfeeding. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided throughout the study and until at least 60 days after last dose of IADA
* Uncontrolled hypertension (i.e., systolic blood pressure /> 180 mm Hg, diastolic blood pressure /> 95 mm Hg). Use of anti-hypertensive agents to control hypertension before C1D1 is allowed
* Patients with poorly controlled diabetes. Poorly controlled diabetes mellitus defined as glycosylated hemoglobin (HbA1c) ≥ 8%; patients with a history of transient glucose intolerance due to corticosteroid administration may be enrolled in this study if all other inclusion/exclusion criteria are met
* Patients with mean of triplicate corrected QT interval (Fridericia`s correction formula /[QTcF/]) /> 450 ms at Screening based on central reading
* Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, unstable cardiac or pulmonary function or acute insufficiency (e.g., symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia), or psychiatric illness or social situation that could limit compliance with study requirements, at the discretion of the investigator

NCT05554406 (добавлено: 2024-06-08)

Testing the Effects of Novel Therapeutics for Newly Diagnosed, Untreated Patients With High-Risk Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)

A Randomized Phase II Study Comparing Cytarabine + Daunorubicin (7 + 3) vs (Daunorubicin and Cytarabine) Liposome, Cytarabine + Daunorubicin + Venetoclax, Azacitidine + Venetoclax, and (Daunorubicin and Cytarabine) Liposome + Venetoclax in Patients Aged 59 or Younger Who Are Considered High-Risk (Adverse) Acute Myeloid Leukemia As Determined by MYELOMATCH; A MYELOMATCH Clinical Trial

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: Augusta University Medical Center; Augusta; Georgia; United States,Banner University Medical Center - Tucson; Tucson; Arizona; United States,Baptist Cancer Center-Grenada; Grenada; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Collierville; Collierville; Tennessee; United States,Baptist Memorial Hospital and Cancer Center-Desoto; Southhaven; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Golden Triangle; Columbus; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Memphis; Memphis; Tennessee; United States,Baptist Memorial Hospital and Cancer Center-Oxford; Oxford; Mississippi; United States,Baptist Memorial Hospital and Cancer Center-Union County; New Albany; Mississippi; United States,Benefis Sletten Cancer Institute; Great Falls; Montana; United States,Billings Clinic Cancer Center; Billings; Montana; United States,Bozeman Health Deaconess Hospital; Bozeman; Montana; United States,Cancer Care Center of O`Fallon; O`Fallon; Illinois; United

×

Критерии включения

* STEP 1 REGISTRATION:
* Participants must have been registered to Master Screening and Re-Assessment Protocol, MYELOMATCH, prior to consenting to this study. Participants must have been assigned to this clinical trial, via MATCHBox, prior to registration to this study.
* Note: Pre-enrollment/diagnosis labs must have already been performed under the MYELOMATCH
* Participants must have newly diagnosed, untreated acute myeloid leukemia (AML) per World Health Organization (WHO) criteria
* Participants must have high-risk (adverse) AML per European LeukemiaNet (ELN) 2017 criteria
* Participants with therapy-related AML (t-AML), or with AML evolving from an antecedent hematologic disorder (such as myeloproliferative neoplasm), or AML with myelodysplasia-related changes (AML-MRC) are eligible
* Acute promyelocytic leukemia is excluded
* Participants with favorable or intermediate risk disease are excluded
* Participants with FLT3 mutations (ITD or TKD) are excluded
* Participants with t(9;22) translocation are excluded
* A single dose of intrathecal chemotherapy is allowed prior to study entry
* Prior anthracycline therapy is allowed but must not exceed a cumulative lifetime dose of 200 mg/m/^2 daunorubicin or equivalent. Prior hypomethylating agent (HMA) exposure is allowed, as long as not for AML diagnosis
* Participants must not have received or be currently receiving any prior therapy for acute myeloid leukemia. Hydroxyurea to control the white blood cells (WBC) is allowed prior to registration and initiation of protocol-defined therapy. All trans retinoic acid (ATRA) given until a diagnosis of acute promyelocytic leukemia is ruled out is also allowed.
* Participants must not be receiving or planning to receive any other investigational agents before completing protocol therapy
* Participants must be between 18 and 59 years of age
* Participants must have Zubrod performance status =/< 3 as determined by a history and physical (H/&P) completed within 14 days prior to registration
* Participants must have a complete medical history and physical exam within 7 days prior to registration
* Participants must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of oral medications
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months prior to registration
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days prior to registration and be on suppressive therapy, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration
* The following tests must be performed within 14 days prior to registration to establish baseline values:
* Complete blood count (CBC)/differential/platelets
* Total bilirubin
* Lactate dehydrogenase (LDH)
* Albumin
* Glucose
* Fibrinogen
* Participants must have adequate kidney function as evidenced by creatinine clearance />= 30mL/min (by Cockcroft Gault) within 28 days prior to registration
* Participants must have adequate liver function as evidenced by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) /< 3.0 x upper limit of normal (ULN), and total bilirubin =/< 2.0 x ULN (or 5.0 x ULN if the participant has a history of Gilbert`s disease) within 28 days prior to registration
* Total bilirubin =/< 2.0 x ULN (or 5.0 x ULN if the participant has a history of Gilbert`s disease) within 28 days prior to registration
* Participants must have adequate cardiac function as determined by echocardiography or MUGA scan with an ejection fraction />= 50% within 28 days prior to registration
* Participants with a prior or concurrent malignancy whose natural history (in the opinion of the treating physician) does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. No concurrent therapies for such malignancy are allowed with the exception of hormonal therapy
* Participants with known history of Wilson`s disease or other known copper-metabolism disorder are excluded
* Participants must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use 2 contraception methods. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods (e.g., hormonal contraceptives /[examples include birth control pills, vaginal rings, or patches/] associated with inhibition of ovulation for at least 1 month prior to taking study drug), "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. A barrier method should be used during this study along with hormonal contraceptives from initial study drug administration to 30 days after the last dose of study drug as drug-drug interaction with venetoclax is unknown
* Participants must have agreed to have specimens submitted for translational medicine (MRD) under the myeloMATCH MSRP and specimens must be submitted
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution`s identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

NCT06326021 (добавлено: 2024-04-18)

Optimised CD33 (FL-33) CAR T Therapy for Refractory/Relapsed Acute Myeloid Leukaemia

Optimised CD33 (FL-33) CAR T Therapy for Refractory/Relapsed Acute Myeloid Leukaemia：a Single-center, Open-label, Non-randomised, Single-arm Phase Ⅰ Clinical Trial

Теги: #Relapsed|Refractory

Локации: BeijingGoBroadH, Beijing, China,BeijingGoBroadH; Beijing; China

NCT06150040 (добавлено: 2023-12-02)

Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX]

A Phase I/II Study to Evaluate the Safety Clinical and Biological Activity of a Humanized Monoclonal Antibody Targeting Netrin-1 (NP137) in Combination With Standard AZACITIDINE+ VENETOCLAX in Patients With Refractory Acute Myeloid Leukemia

Теги: #FLT3 mutation , #Relapsed|Refractory

Локации: Centre Leon Berard, Lyon, France,Centre Léon Bérard; Lyon; France

×

Критерии включения

I1. Adult is ≥ 65 years of age at the time of signing the ICF (Inform Consent Form)
I2. Histologically confirmed acute myeloid leukemia (AML) as defined by the 2022 World Health Organization (WHO) Classification.
I3. Patient previously untreated for AML (except with the first 2 cycles of his/her current A+V treatment) and who is considered as ineligible for induction regimen and intensive chemotherapy due to age and other comorbidity that the physician judges to be incompatible with such treatment:
OR Patient with expected poor prognosis under intensive /induction chemotherapy (e.g. with complex karyotype) OR "No-go" patients according ALFA decision tool (/[e.i: patient with Adverse cytogenetics ≥1 of the following: mKRAS, mTP53)
Note : Patients with favourable-risk cytogenetics with intensive chemotherapy are not eligible, such as:
* t(8;21)(q22;q22.1); RUNX1-RUNX1T1
* inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
* Mutated NPM1 without FLT3-ITD or with FLT3-ITDlow†
* Biallelic mutated CEBPA
I4. Patients under treatment by A+V treatment as standard first line treatment for AML with no CR nor CRi after 2 cycles of AZACITIDINE +VENETOCLAX.
I5. Patient must be, in the judgment of the investigator, an appropriate candidate for an experimental therapy i.e. with no available other standard treatment or options except palliative care.
I6. Participant must have a life expectancy of at least 12 weeks.
I7. Participants has with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 are eligible to the safety run-in part whatever their age. Then for the expansion part, patient with ECOG PS (Performance Status) of 0 to 2 for subject ≥ 75 years OR of 0 to 3 for subject ≥ 65 to 74 years of age are eligible.
I8. Demonstrate adequate cardiac function:
* QTc (corrected QT interval) ≤470ms
* Resting systolic BP /<160mmHg
* Resting diastolic BP /<100mmHg
* LVEF (left ventricular ejection fraction) ≥50% as determined by multiple-gated acquisition (MUGA) scan or transthoracic echocardiogram.
I9. Demonstrate adequate organ function as defined in table below, all screening laboratory tests should be performed within 7 days prior Cycle 1 day 1 :
* White Blood Cells Count /< 25 × 109/L or lower; use of leukapheresis or hydroxyurea is permitted to achieve this concentration before Cycle 1 Day 1, at the discretion of the treating physician and according to institutional practice. (see exclusion criteria E6)
* Creatinine clearance Calculated creatinine clearance ≥30 mL/min determined by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula OR via urine collection for 24-hour creatinine clearance or serum creatinine ≤ 2 upper limit of normal (ULN)
* Bilirubin Total bilirubin /< 2 × the upper limit of normal (ULN) If total bilirubin ≥ 2 ULN, Direct Bilirubin must be /< 2 x ULN unless considered due to leukemic organ involvement(/< 5 ULN) and with the following Exception: Patients with known Gilbert disease who have serum bilirubin level ≤ 3 ULN may be enrolled.
* SGOT (serum glutamate oxaloacetate transaminase) (AST) and SGPT (serum glutamate pyruvate transaminase) (ALT) ≤ 3 x ULN unless considered due to leukemic organ involvement (/< 5 ULN)
I10. Patient has no evidence of spontaneous tumor lysis syndrome (TLS) before NP137 introduction.
I11. Female subjects must be either:
* Postmenopausal; defined no menses for ≥ 12 months without an alternative medical cause; OR
* Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
I12. Non-sterile male subjects must use contraceptive methods with partner(s) prior to beginning study drug administration and continuing up to 3.5 months /[106 days/] after the last dose of NP137. Male subjects must agree to refrain from sperm donation from initial study drug administration during this same period.
I13. Patient must understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures.
I14. Patient must be able and willing to comply with study visits and procedures as per protocol.
I15. Patients must be covered by a medical insurance

×

Критерии исключения

E1. Patient who is eligible for any curative therapy including but not limited to induction / intensive chemotherapies, CAR-T cell therapy and agrees to receive this therapy.
E2. Patient previously treated for AML with a hypomethylating agent and/or other chemotherapeutic agents either conventional or experimental for AML before NP137 introduction.
E3. Patient who has acute promyelocytic leukemia.
E4. Patient who experienced:
* Any persisting non hematological grade ≥ 3 AZACITIDINE AND VENETOCLAX related Adverse events before C1D1.
* Any vascular disorder grade ≥ 3 within 6 months prior C1D1.
E5. History of severe allergic anaphylactic reactions (≥ grade 3) to one of the components of the study drugs or to humanized antibodies or premedication and/or any of their excipients.
E6. Prior therapy or needs to be treated with a forbidden concomitant/concurrent therapies/procedures including:
* Any investigational agent or have used an investigational device.
* Major surgery within 4 weeks of start of study treatment. Participants must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment, C1D1.
* Anti-cancer treatment other than those specified in the protocol i.e. AZACITIDINE + VENETOCLAX.
* Live or live-attenuated vaccine within 30 days prior to the first dose of study treatments. Note: Inactivated vaccine are allowed.
Note:
* During the safety run in phase, Hydroxyurea is authorized prior C1D1 but a wash-out period of 2 days or 5/*t1/2 before C1D1 whatever • shorter is required.
* During the expansion phase, the use of hydroxyurea for patients with rapidly proliferative disease is allowed during the course of cycle 1 at the discretion of the treating physician and according to institutional practice
E7. Active or untreated central nervous system involvement.
E8. Other invasive malignancy in the last 2 years except for those with a minimal risk of metastasis or death such as adequately managed in-situ carcinoma of the cervix, basal or squamous cell skin cancer, localized prostate cancer or ductal carcinoma in situ treated with curative intent, previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
E9. Patients with any other known concurrent severe and/or uncontrolled medical condition including but not limited to diabetes, cardiovascular disease including hypertension, renal disease, or active uncontrolled infection, which could compromise participation in the study. For active infection requiring systemic therapy or fever likely secondary to infection within prior 48 hours: prophylactic antibiotics or prolonged course of IV antibiotics for controlled infection are allowed.
E10. Patients with uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, clinically significant and uncontrolled arrhythmia as judged by the treating physician.
E11. Patient with evidence of uncontrolled active infection requiring systemic therapy (viral, bacterial or fungal).
E12. Patients known to be positive to HIV (testing will be performed a screening).
E13. Patients known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. Hepatitis B or C testing is not required and subjects with serologic evidence of prior vaccination to Hepatitis B virus (i.e., HBs Ag, anti-HBs+ and anti-HBc-) may participate.
Patients placed under a legal protection regimen: Judicial Safeguards, curatorship or guardianship.

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