OncoTrials - мониторинг клинических исследований

Описание

The study will evaluate the progression-free survival benefit of duvelisib monotherapy as compared to investigator`s choice of gemcitabine or bendamustine in participants with relapsed/refractory nodal T cell lymphoma with TFH phenotype.

Критерии включения

• * Pathologically confirmed nodal T cell lymphoma with TFH phenotype according to the criteria of the World Health Organization classification (Swerdlow 2017, Alaggio 2022) including any one of Angioimmunoblastic T cell lymphoma (AITL), follicular T cell lymphoma, and other nodal peripheral T cell lymphoma (PTCL) with a TFH phenotype.
• * Relapsed or refractory to at least 1 prior systemic, cytotoxic therapy for T cell lymphoma.
• * Measurable disease as defined by Lugano 2014 criteria (Cheson 2014) for T cell lymphoma.

Критерии исключения

• * Cutaneous-only disease.
• * Received prior allogeneic transplant any time in the past or received autologous transplant within 60 days prior to the first dose of study drug.
• * Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor.
• * Prior exposure to planned study treatment investigator`s choice therapy (gemcitabine or bendamustine) within 60 days prior to the first dose of study drug.
• Other protocol-defined criteria apply.

Описание

This is a multi-center, open-label, non-randomized, single-arm clinical trial. Refractory/relapse T-NHL patients are treated with autologous and allogeneic CD7 CAR T-cell therapy. The primary objective is to prospectively evaluate the safety of CD7 CAR T cell bridging to HSCT in the treatment of r/r T-NHL. The primary endpoint is the type and incidence of dose limiting toxicity (DLT) within 21 days after CD7 CAR-T cell infusion. A total of 36 subjects is estimated to be enrolled.

Критерии включения

• (Patients who met all the inclusion criteria were eligible for enrolment):
• * Relapsed or refractory CD7-positive T-cell lymphomas that were treated with with standard chemotherapy, with poor prognosis from currently available treatments at and no available treatment options (e.g., HSCT or chemotherapy);
• * Male or female, age 14-70;
• * Eastern Cooperative Oncology Group (ECOG) Physical Status Score 0-2;
• * life expectancy is at least 60 days;
• * Subjects should be capable of understanding and signing the informed consent form prior to any screening procedures. Subjects are willing to follow the study visit schedule and associated study procedures as specified in the protocol. Candidates between the ages of 19-70 years old will need to be sufficiently aware of and capable of signing the informed consent form; underage candidates between the ages of 14-18 years old will need to be sufficiently aware of the informed consent form and their legal guardian will also need to sign the informed consent form separately.

Критерии исключения

• (Patients who fulfil any of the following criteria may not be enrolled):
• * Patients with history of allogeneic HSCT but PBMNC is not available from prior- transplant donor for preparation of CAR T cells and peripheral blood tumour load />30%; patients without history of allogeneic HSCT and peripheral blood tumour load />30%;
• * Intracranial hypertension or cerebral impaired consciousness;
• * Symptomatic heart failure or severe arrhythmia;
• * Symptoms of severe respiratory failure;
• * With other types of malignancy;
• * Diffuse intravascular coagulation;
• * Serum creatinine and/or urea nitrogen ≥ 1.5 times the normal value;
• * With sepsis or other uncontrollable infection;
• * Suffering from uncontrollable diabetes mellitus;
• * Severe mental disorders;
• * Have significant intracranial lesions on cranial MRI;
• * Organ transplantation (excluding haematopoietic stem cell transplantation) history;
• * Female patients (patients of childbearing potential) with positive blood HCG test;
• * Hepatitis (including hepatitis B and C) and positive screening for AIDS and syphilis.

Описание

This research is being done to evaluate tazemetostat in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy as a possible treatment for peripheral T-Cell Lymphoma (PTCL).

The name of the study drugs involved in this study are:

* Tazemetostat (a type of inhibitor for Enhancer of Zeste Homolog 2 (EZH2))
* Standard of care CHOP therapy:

* Cyclophosphamide (a type of alkylating agent)
* Doxorubicin (a type of anthracycline antibiotic)
* Vincristine (a type of vinca alkaloid)
* Prednisone (a type of corticosteroid)
* Standard of care BEAM conditioning regimen for autologous stem cell transplant:

* Carmustine (a type of alkylating agent)
* Etoposide (a type of Topoisomerase II inhibitor)
* Cytarabine (a type of antineoplastic)
* Melphalan (a type of alkylating agent)

Критерии включения

• * Participants must have histologically or cytologically confirmed peripheral T cell lymphoma of one of the following subtypes: PTCL-NOS, Follicular helper T-cell lymphoma (ICC 2022) or Nodal T-follicular helper (TFH) cell lymphoma by (WHO 2022) which includes follicular helper T-cell lymphoma, AITL and follicular helper T cell lymphoma, follicular type, EATL, MEITL. All pathology will be reviewed at BWH. BWH review is not required prior to enrollment and patients may be enrolled based upon local pathology analysis. Ten blank slides will be required from outside tumor biopsy for correlative studies.
• * No prior treatment for T NHL with the exception of one cycle of CHOP or CHOEP or 7 days of corticosteroids at a dose of up to prednisone 60 mg or equivalent for palliation of disease related symptoms so long as the corticosteroids are discontinued prior to tazemetostat prephase or cycle 1 of treatment if not receiving the prephase.
• * At least one bi-dimensionally measurable lesion, defined as />1.5 cm in its longest dimension as measured by CT.
• * Age ≥18 years.
• * ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• * Participants must have adequate organ and marrow function as defined below:
• * absolute neutrophil count ≥1,000/mcL (750 mcl if bone marrow involvement with lymphoma)
• * platelets ≥75,000/mcL (25,000 if bone marrow involvement with lymphoma)
• * total bilirubin ≤ institutional upper limit of normal (ULN)
• * AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
• * creatinine ≤ 1.5 x institutional ULN OR
• * glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2
• * Because the effects of tazemetostat on human immunodeficiency virus (HIV)-infected participants and anti-retroviral therapy is unknown, patients with known HIV infection are not eligible for this trial.
• * For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• * Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment, are not eligible.
• * Left ventricular ejection fraction of /> 50% as assessed by echocardiography or multi-gate acquisition (MUGA) scan.
• * The effects of tazemetostat on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men 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. For women of childbearing potential, a negative serum pregnancy test result within 7 days prior to commencement of dosing. Women who are considered not to be of childbearing potential are not required to have a pregnancy test.
• * Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of tazemetostat administration.Women should use effective contraceptive methods beginning ≥28 days prior to initiating, during tazemetostat treatment, and for at least 6 months after the final dose of tazemetostat
• * Ability to understand and the willingness to sign a written informed consent document.

Критерии исключения

• * Participants who have had chemotherapy for T cell lymphoma prior to entering the study (except 1 cycle of CHOP/CHOEP as noted above). Prior radiotherapy may be allowed after discussion with the sponsor-investigator so long as the area radiated was not the only measurable site of disease.
• * Participants who are receiving any other investigational agents.
• * Patients with known central nervous system involvement with lymphoma
• * History of allergic reactions attributed to compounds of similar chemical or biologic composition to tazemetostat or other agents used in study.
• * Prior organ transplantation.
• * Current motor or peripheral neuropathy with grade />1.
• * History of other malignancy that could affect compliance with the protocol or interpretation of results. Exceptions include:
• * Patients with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study are eligible.
• * Patients with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for /> 2 years prior to enrollment are eligible.
• * Patients with low-grade, early-stage prostate cancer (Gleason score 6, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible.
• * Uncontrolled intercurrent illness.
• * Pregnant women and women intending to become pregnant are excluded from this study because chemotherapeutic agents used in this study have 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 tazemetostat, breastfeeding should be discontinued if the mother is treated with tazemetostat.
• * Evidence of significant, uncontrolled, concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina)
• * Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
• * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or significant infections within 2 weeks before the start of Cycle 1.
• * Inability to swallow pills.
• * Because no dosing or adverse event data are currently available on the use of tazemetostat in combination with CHOP in participants /<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.

Описание

Evaluate the Safety, Pharmacokinetics and Efficacy of CHT101 in Subjects With Relapsed or Refractory T or B Cell Hematological Malignancies

Критерии включения

• (abbreviated):
• 1. Willing and able to provide written informed consent.
• 2. Aged 18 to 70 years, male or female.
• 3. Confirmed CD70 positive in tumor tissue by immunohistochemistry (IHC).
• 4. Only the following subtypes of hematological malignancies with measurable disease will be enrolled:
• 1. Peripheral T cell lymphoma (including peripheral T cell lymphoma NOS, angioimmunoblastic T cell lymphoma, anaplastic large cell lymphoma, etc.) who have failed ≥1 line of systemic therapy.
• 2. Cutaneous T cell lymphoma (including mycosis fungoides (MF) or Sézary syndrome (SS) /[stage ≥IIB with disease involving two or more compartments or single-compartment disease with large-cell transformation/]) who have failed ≥2 lines of systemic therapies.
• 3. Aggressive B cell lymphoma who are refractory or relapsed post ≥2 lines of systemic therapies which contain anti-CD20 antibody and anthracyclines.
• 4. Indolent B cell lymphoma who are refractory or relapsed post ≥2 lines of systemic therapies which contain anti-CD20 antibody.
• 5. Chronic lymphocytic leukemia (CLL) who are refractory or relapsed post ≥2 lines of systemic therapies which contain BTK inhibitor and BCL-2 inhibitor.
• 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• 6. Estimated life expectancy ≥12 weeks.
• 7. Female patients of childbearing potential and male patients must agree to use a highly effective method of contraception from signing ICF through 2 years after last CHT101 infusion.

Критерии исключения

• (abbreviated):
• 1. History or presence of CNS metastasis, or clinically relevant CNS pathology such as seizure, stroke, severe brain injury, etc.
• 2. History of solid organ transplantation.
• 3. Prior treatment with CD70-targeting agents.
• 4. Prior treatment with CAR-T or other cellular/gene therapies.
• 5. Ongoing bacterial, viral or fungal infection requiring systemic anti-infectives.
• 6. Active autoimmune disease requiring immunosuppression.

Описание

This is an open-label, phase 2 randomized study to evaluate the efficacy, safety, pharmacokinetics (PK) and pharmadynamics (PD), of PTX-100 monotherapy at 500 or 1000 mg/m2 in patients with relapsed/refractory Cutaneous T-Cell Lymphoma (CTCL).

PTX-100 will be administered by IV infusion over 60 minutes on days 1 to 5 of a 14-day cycle for 4 cycles, then 21 day cycle thereafter. Subjects will be treated or followed up, if subjects discontinue treatment, for up to 18 months.

Критерии включения

• 1. Adult patient ≥18 years of age at the time of signing the informed consent.
• 2. Patient is capable of giving adequate signed informed consent
• 3. Have a confirmed diagnosis of CTCL with histological confirmation
• 4. Patients must have greater than or equal to Stage Ib disease.
• 5. Has received and failed (or intolerant of) at least 2 prior lines of prior systemic therapy for their disease.
• 6. Has measurable disease defined by at least one of the following, within 28 days prior to start of study treatment: by evaluable by mSWAT or quantifiable by flow cytometry or morphology in blood or measurable by Lugano Criteria.
• 7. On a stable dose of systemic corticosteroid (/< 10 mg prednisone or equivalent) are permitted. Participants on a stable dose of topical corticosteroids are permitted.
• 8. Washout period- must be 2 weeks (4 weeks for monoclonal antibodies) or 5 -half-lives (whichever is longer) since any prior anti-cancer therapy.
• 9. Must be human T-cell lymphotropic virus type 1 (HTLV1) negative.
• 10. Has an ECOG PS of 0 to 2.
• 11. Life expectancy of 3 months or greater
• 12. Has adequate bone marrow function.
• 13. Has adequate hepatic function.
• 14. Has adequate Renal function.
• 15. Has adequate coagulation function.
• 16. Patients with Human Immunodeficiency virus (HIV) must be on established and stable effective anti-retroviral therapy for at least 4 weeks and have an HIV viral load of less than 400 copies/mL.
• 17. Male patients are eligible to participate if they agree to use a highly effective contraception during the treatment period and for at least 3 months after the last dose of study treatment and refrain from donating sperm during this period.
• 18. Female patients are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies:
• -Not a woman of childbearing potential (WOCBP).
• * OR
• * A WOCBP who agrees to use a contraceptive method that is highly effective (with a failure rate of /< 1% per year) or be abstinent from heterosexual intercourse as their preferred method and usual lifestyle, beginning the time of informed consent, during the treatment period and for at least 3 months after the last dose of study treatment.
• 19. A WOCBP must have a negative serum pregnancy within 72 hours of the first dose of study treatment.
• 20. Must be willing and able to adhere to the study as judged by the Investigator.

Критерии исключения

• 1. Patients with known central nervous system involvement.
• 2. Patients who require the use of strong inhibitors or inducers of CYP enzymes or transporters (e.g., CYP3A4, 2D6, 2C19) or (P-gp, BCRP, OATP1B1, OATP1B3, OAT1. OAT3, OCT2, MATE1 and MATE2-K). Patients who are receiving these medications at Screening can be enrolled into the trial if they discontinue them for at least 14 days or 5 half-lives, whichever is longer, before they commence PTX-100. An alternative pharmacological treatment should be instituted by the treating clinician based on clinical judgement.
• 3. Significant cardiovascular disease. A history of, or concurrent interstitial lung disease or severely impaired lung function.
• 5. Active viral, bacterial, fungal infection or other serious infection requiring ongoing systemic treatment. Routine antimicrobial prophylaxis is permitted.
• 6. Medical history of another malignant tumor within the past 5 years. Exceptions are patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ who have undergone curative therapy with no evidence of disease.
• 7. On an immunomodulatory drug for concomitant or intercurrent conditions or who have received any of these agents within 4 weeks of baseline.
• 8. Patients with active viral (any etiology) hepatitis are excluded. However, patients with serologic evidence of chronic hepatitis B virus (HBV) infection (defined by a positive hepatitis B surface antigen test and a positive anti-hepatitis core antigen antibody test) who have a viral load below the limit quantification (HBV deoxyribose nucleic acid titer /< 1000 cps/mL or 200 IU/mL) and are not currently on viral suppressive therapy may be eligible and should be discussed with the Medical Monitor. Patients with a history of hepatitis C virus infection who have completed curative antiviral treatment and have a viral load below the limit of quantification may be eligible and should be discussed with the Medical Monitor.
• 9. A history or current evidence of any condition, laboratory abnormality or other circumstance that might confound the results of the study or interfere with patient participation for the full duration of the study.
• 10. Prior allogeneic or autologous hematopoietic transplantation 11. Has a known psychiatric disorder that would interfere with compliance with the requirements of the study.
• 12. Is a consumer of illicit or recreational drugs or has a recent history (within the last year) of drug or alcohol abuse or dependence that in the judgment of the Investigator, would interfere with compliance with the requirements of the study.

Описание

This is an open-label, phase Ib study evaluating the combination treatment of sintilimab and linperlisib in patients with relapsed or refractory extranodal natural killer/T-cell lymphoma (NKTCL).

Критерии включения

• 1. Pathologically confirmed extranodal NKTCL.
• 2. Voluntary participation in the clinical study; fully understand the study, and have signed the written informed consent form.
• 3. Age ≥ 18 years.
• 4. Relapsed or refractory NKTCL after failure of at least one line of asparaginase-based chemotherapy or chemoradiotherapy regimen.
• 5. ECOG performance status: 0-2.
• 6. Estimated survival time ≥ 3 months.
• 7. At least one measurable lesion according to the Lugano 2014 lymphoma evaluation criteria.
• 8. Adequate organ and bone marrow function.

Критерии исключения

• 1. Patients previously treated with PI3K inhibitors.
• 2. Patients with hemophagocytic syndrome.
• 3. Patients known to be allergic to any component of monoclonal antibodies.
• 4. Patients with a history of other malignancies within the past 5 years or concurrent malignancies (excluding basal cell carcinoma of the skin).
• 5. Patients with aggressive NK-cell leukemia or central nervous system involvement.
• 6. Patients who have participated in other drug clinical trials within 4 weeks prior to the start of this study or have received anti-tumor treatment within 4 weeks before the study initiation.
• 7. Patients with clinically significant gastrointestinal abnormalities that may affect drug intake, transport, or absorption (e.g., inability to swallow, chronic diarrhea, intestinal obstruction) or patients who have undergone total gastrectomy.
• 8. Patients with a history of interstitial lung disease (except for asymptomatic interstitial lung disease caused by radiotherapy).

Описание

This is a phase I/II clinical trial to evaluate the efficacy and safety of Golidocitinib combined with Pomalidomide for relapsed/refractory peripheral T-cell lymphoma.

Критерии включения

• * Patients must demonstrate a comprehensive understanding of the study protocol, voluntarily consent to participation, and execute the informed consent document.
• * Inclusive of both genders, participants must be aged 18 years or older and not exceed 80 years of age.
• * Histopathological confirmation of peripheral T-cell lymphoma (PTCL) must adhere to the World Health Organization (WHO) 2016 classification criteria. This encompasses a range of PTCL subtypes, including but not limited to peripheral T cell lymphoma not otherwise specified (PTCL NOS), vascular immunoblastic T cell lymphoma (AITL), NK/T cell lymphoma, anaplastic large cell lymphoma ALK positive (ALCL ALK+), anaplastic large cell lymphoma ALK negative (ALCL ALK-), enteropathy-associated T-cell lymphoma, hepato-splenic T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, and other subtypes deemed eligible for study participation by the investigators.
• * Subjects must exhibit relapsed or refractory disease following prior systemic therapy, which may include autologous hematopoietic stem cell transplantation. Relapse is characterized by disease recurrence post-complete response (CR), whereas refractory disease is indicated by stable disease (SD) or progressive disease (PD) following systemic chemotherapy, or by the absence of CR upon treatment completion necessitating further intervention.
• * At least one lesion must be present that is evaluable or measurable according to the Lugano2014 criteria: for lymph node lesions, the minimum measurable length is 1.5cm; for non-lymph node lesions, extra-nodal lesions must exceed 1.0cm in length.
• * Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score ranging from 0 to 2.
• * Laboratory parameters must meet the following criteria: (1) absolute neutrophil count (ANC) of at least 1.5×10/^9/L; (2) platelet count (PLT) of at least 75×10/^9/L (with a minimum of 50×10/^9/L for patients with bone marrow infiltration); (3) hemoglobin (HB) level of at least 80 g/L; (4) serum total bilirubin (TBIL) not exceeding 1.5 times the upper limit of normal (ULN); (5) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels not exceeding 2.5 times the ULN; (6) serum creatinine (Scr) not exceeding 1.5 times the ULN.
• * Participants must not have undergone radiotherapy, chemotherapy, targeted therapy, or hematopoietic stem cell transplantation within the 3 weeks preceding study enrollment.
• * Investigators must assess that the subject has a life expectancy of at least six months.

Критерии исключения

• * Presence of hemophagocytic syndrome.
• * Involvement of the central nervous system or meninges by lymphoma.
• * A history of malignant tumors within the past five years, with the exception of locally curable tumors that have been subjected to radical treatment (e.g., basal or squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast).
• * History of any of the following treatments:(1) Allogeneic hematopoietic stem cell transplantation prior to the administration of the investigational drug; (2) Autologous hematopoietic stem cell transplantation within six months preceding study drug administration; (3) Previous use of golidocitinib or pomalidomide; (4) Current use of vitamin K antagonists, antiplatelet drugs, anticoagulants (or unable to discontinue within one week prior to study commencement); (5) Requirement for systemic glucocorticoid therapy or other immunosuppressive therapy for any condition within 14 days prior to study initiation; topical, ocular, intraarticular, intranasal, and inhaled glucocorticoids are permitted; short-term (≤7 days) glucocorticoid use for prophylactic treatment or non-autoimmune diseases is allowed; (6) Cytotoxic chemotherapy must not have been terminated within 21 days before the start of the study; (7) Received systemic antineoplastic therapy (including macromolecular monoclonal antibodies and immunotherapy drugs) within four weeks of study initiation; (8) Undergone major surgery (excluding vascular access surgery) or experienced serious trauma within four weeks before the start of the study; or received radiation therapy within three weeks; (9) Received other toxin/isotope-immune antibody conjugates within ten weeks; (10) For other types of new drug use, the researcher shall make a determination after comprehensive assessment; (11) Received an experimental drug or investigational drug in another trial within 30 days prior to study commencement; (12) Received live vaccines (except attenuated influenza vaccines) 28 days prior to study drug administration.
• * Active infections, including: (1) Known active/latent tuberculosis, including a positive tuberculin skin test or findings on plain chest X-ray/CT (positive skin test results should exhibit an induration diameter greater than 10 mm, or as per local clinical criteria); (2) Known history of Human Immunodeficiency Virus (HIV) infection and/or acquired immunodeficiency syndrome; (3) Patients with active chronic hepatitis B or hepatitis C. Hepatitis B Surface Antigen (HBsAg) must be further tested with Hepatitis B Virus (HBV) DNA titer (not to exceed 1000 IU/mL) at the screening stage. Enrollment in the trial is only possible after excluding active hepatitis B or C infections requiring treatment. Hepatitis B carriers, patients with stable hepatitis B after drug treatment (with a DNA titer not exceeding 1000 IU/mL), and cured hepatitis C patients are eligible for enrollment. (For included hepatitis B patients, entecavir and other anti-hepatitis B virus treatments should be administered orally as per guidelines); (4) Active viral infections other than hepatitis B and C (e.g., herpes zoster, cytomegalovirus); (5) Infections necessitating oral or intravenous antimicrobial therapy; (6) Bacterial infections within 30 days, including pneumonia.
• * Active autoimmune diseases requiring systemic treatment within the past two years (hormone replacement therapy not considered systemic treatment, such as type I diabetes, hypothyroidism managed with thyroxine replacement alone, adrenal or pituitary insufficiency requiring only physiological glucocorticoid replacement); patients with autoimmune diseases not requiring systemic treatment in the past two years may be enrolled.
• * Uncontrolled cardiac clinical symptoms or diseases, such as: i. New York Heart Association (NYHA) class /> 2 heart failure ii. Unstable angina pectoris iii. Myocardial infarction within one year iv. Patients with clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
• * Prior interstitial lung disease (except for asymptomatic interstitial lung disease induced by radiotherapy).
• * Presence of unresolved adverse drug reactions greater than CTCAE grade 1 (excluding alopecia) before study initiation.
• * Patients with hypersensitivity to golidocitinib or pomalidomide/capsule excipients or other chemical analogs; patients with a known history of severe allergic reactions to monoclonal antibodies (CTCAE≥3) and uncontrolled allergic asthma.
• * Subjects requiring supportive treatment for refractory nausea, vomiting, chronic gastrointestinal disorders, dysphagia, or prior surgical removal of intestinal segments that may impede adequate drug absorption.
• * Pregnant and lactating women and individuals of childbearing age who are unwilling to practice contraceptive measures.
• * Individuals with psychiatric illnesses or those incapable of providing informed consent.
• * Deemed ineligible for study participation by the researcher.

Описание

To learn if the study drug golidocitinib given alone or in combination with the standard drug combination therapy called CHOP can help to control PTCL.

Критерии включения

• * Provision of a signed and dated, written informed consent form prior to any study specific procedures, sampling, and analyses.
• * Submission of the tumor block or unstained slides from an excisional or core biopsy from nodal or extra-nodal lymphoma tissue (archived or newly obtained sample) is required for retrospective central confirmation of tumor histological subtype.
• * Aged ≥ 18 years old.
• * Participants must exhibit Eastern Cooperative Oncology Group (ECOG) performance status 0-2 with no deterioration over the previous 2 weeks.
• * Predicted life expectancy ≥ 12 weeks.
• * Participants must have histologically confirmed peripheral T-cell lymphoma by MD Anderson pathology review according to the 2016 revision of the World Health Organization classification of lymphoid neoplasms53. Eligible histological subtypes are restricted to the following:
• * PTCL, not otherwise specified (PTCL, NOS) (the proportion of PTCL-NOS subtype will not exceed 30% of all enrolled)
• * Angioimmunoblastic T-cell lymphoma (AITL)
• * Follicular T cell lymphoma
• * PTCL with T follicular helper (TFH) phenotype
• * Participants must have measurable disease according to the 2014 Lugano classification, which is defined as lymphomatous nodes, nodal masses, or other lymphomatous lesions are measurable in two diameters (longest diameter /[LDi/] and shortest diameter perpendicular to the LDi /[SDi/]) on CT scans, and also with LDi as below:
• * A measurable node must have an LDi greater than 1.5 cm.
• * A measurable extranodal lesion should have an LDi greater than 1.0 cm.
• * Participants must be treatment naïve with no prior systemic treatment for T-cell lymphoma (i.e., PTCL). Participants could be transplant eligible or ineligible upon their entries to this study.
• * Adequate bone marrow reserve and organ system functions, as outlined below:
• * Absolute neutrophil count (ANC) ≥ 1 ×109/L (≥0.5 ×109/L if documented bone marrow involvement with lymphoma) independent of growth factor support within 7 days of study entry.
• * Platelets ≥ 75 × 109/L (or ≥ 50 × 109/L if documented bone marrow involvement with lymphoma) independent of growth factor support or transfusion within 7 days of study entry.
• * Hemoglobin ≥ 8 g/dL
• * Total bilirubin ≤ 1.5 ×ULN if no liver involvement or ≤ 3 ×ULN in the presence of documented Gilbert`s Syndrome (unconjugated hyperbilirubinemia) or liver involvement.
• * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 ×ULN if with document hepatic involvement with lymphoma.
• * Creatinine ≤ 1.5 × ULN, OR calculated or measured creatinine clearance ≥ 50 mL/min as calculated by the Cockcroft-Gault method, or 24-hour measured urine creatinine clearance ≥ 50 mL/min.
• * LVEF ≥ 50% assessed by ECHO or MUGA.
• * Participants should have the ability and willingness to comply with the study and follow up.
• * The effects of golidocitinib on the developing human fetus are unknown. For this reason and because JAK1 inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men 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. This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the participants presents with an applicable exclusionary factor which may be one of the following:
• * Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• * History of hysterectomy or bilateral salpingo-oophorectomy.
• * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
• * History of bilateral tubal ligation or another surgical sterilization procedure.
• * Approved methods of birth control are as follows: 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. Not engaging in sexual activity for the total duration of the trial and the drug 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.
• * Women treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of golidocitinib administration. If female patients wish to mother children, they should be advised to arrange for freezing of eggs prior to the start of study treatment.
• * Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of golidocitinib administration. Men must refrain from donating sperm during their participation in the study and at least for 6 months after the last treatment. If male patients wish to father children, they should be advised to arrange for freezing of sperm samples prior to the start of study treatment.

Критерии исключения

• Participants must not enter the study if any of the following exclusion criteria are fulfilled:
• * Intervention with any of the following:
• * Any investigational anti-cancer agents or anti-cancer study drugs from a previous clinical study.
• * Any cytotoxic chemotherapy from a previous treatment regimen.
• * Corticosteroids at dosages equivalent to prednisone /> 40 mg/day within 7 days of the start of the study treatment.
• * Major surgery procedure (excluding placement of vascular access), or significant traumatic injury within 4 weeks of the first dose of study treatment, or have an anticipated need for major surgery during the study.
• * Prior treatment with a JAK or STAT3 inhibitor.
• * Prior treatment with any onco-immunotherapy in 28 days prior to first dosing of golidocitinib (e.g., immune checkpoint inhibitors PD-1, PD-L1, CTLA4).
• * Live vaccines within 28 days prior to first dose.
• * Participants currently receiving (or unable to stop use at least 1 week prior to receiving the first dose) medications or herbal supplements known to be Potent inhibitors or inducers of CYP3A .
• * Central nervous system or leptomeningeal lymphoma given the lack of evidence of CNS penetrance of the investigational drug.
• * Participants with severely decreased lung function (i.e. any parameter of FEV1, and DLCO /< 60% of predicted value). Past medical history of pneumonitis, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
• * Participants with disease condition which requires the treatment of immunosuppressants, biologics, or NSAIDs (non-steroid anti-inflammatory drugs).
• * Active infections including
• * History of known active tuberculosis (TB).
• * Known infection with human immunodeficiency virus (HIV).
• * Known active hepatitis B or hepatitis C infection as follows
• * Active viral infections (i.e., zoster) other than hepatitis B or C.
• o Infections requiring oral or intravenous antimicrobial therapy or interferon within 14 days.
• * Any of the following cardiac criteria:
• * Congestive heart failure (CHF) per New York Heart Association (NYHA) classification /> Class II .
• * Clinically significant valvular diseases, hypertrophic or constrictive cardiomyopathy.
• * Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third degree heart block, and second-degree heart block, PR interval /> 250 msec.
• * Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• * Acute Myocardial Infarction (AMI) within 6 months prior to starting treatment, unstable angina or new-onset angina.
• * Participants with heart transplant.
• * Mean resting corrected QTcF interval />450 ms on screening electrocardiogram (ECG).
• * Participants with factors that increase the risk of QT prolongation or arrhythmic events (e.g., congenital long QT syndrome, any concomitant medication known to prolong the QT interval or family history of long QT interval syndrome or unexplained sudden death under 40 years of age in first degree relatives).
• * Participants with acute thrombotic diseases such as pulmonary embolism (PE) and deep venous thrombosis (DVT) within 90 days. Participants with remote history (/>6 months) of provoked PE or DVT (e.g., line-associated DVT; DVT or PE after surgical procedure), and participants on appropriate anticoagulation for 90 or more days from the event will not be excluded.
• * Another malignancy within 5 years prior to enrollment with the exception of adequately treated in-situ carcinoma of the cervix, uterus, basal or squamous cell carcinoma or non-melanomatous skin cancer.
• * Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of golidocitinib.
• * History of hypersensitivity to active or inactive excipients of golidocitinib or drugs with a similar chemical structure or class.
• * As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension or active bleeding diatheses. Screening for chronic conditions is not required.
• * Concurrent conditions that in the investigator`s opinion would jeopardize compliance with the protocol.
• * Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
• * All participants must avoid concomitant use of medications, herbal supplements and/or ingestions of foods with known potent inducer/inhibitory effects on CYP3A activity whenever feasible. Such drugs must have been discontinued for an appropriate period before they enter screening and for a period after the last dose of golidocitinib. Guidance on medications to avoid, medications that require close monitoring and on washout periods.
• * Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• * Pregnant women are excluded from this study because golidocitinib is a JAK1 inhibitor agent 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 golidocitinib, breastfeeding should be discontinued if the mother is treated with golidocitinib. These potential risks may also apply to other agents used in this study.

Описание

This is a single arm, two-stage, Phase 2, open-label, multicenter study of MB-105 in patients with CD5 Positive (CD5+) Relapsed / Refractory T-cell Lymphoma (r/r TCL). This study will apply a Simon two-stage optimal design.

Критерии включения

• 1. Male or female ≥ 18 years of age.
• 2. Patients with r/r TCL per WHO 2022 criteria.
• 1. r/r CTCL that has failed ≥ 2 prior lines of standard of care (SoC) therapy.
• 2. r/r PTCL that has failed ≥ 1 prior lines of SoC therapy. Note: patients with CD30+ disease should have received brentuximab vedotin.
• 3. Has available tumor tissue or willing to undergo biopsy procedure.
• 4. CD5 positivity confirmed by local laboratory using an approved diagnostic test or LDT.
• 5. Karnofsky performance score ≥ 70% or higher.
• 6. Prior CAR T-cell therapy must have occurred /> 60 days prior to study enrollment and must have no evidence of CAR persistence.
• 7. Measurable or detectable disease
• 1. PTCL per Lugano criteria
• 2. CTCL per Global (ISCL/EORTC/USCCL) criteria.
• 8. Prior autologous or allogenic hematopoietic stem cell transplant (HSCT) must have occurred more than 60 days prior to study enrollment.
• 9. Adequate bone marrow function defined as:
• 1. Absolute neutrophil count (ANC) ≥ 1500/μL (≥ 1000/μL for patients with prior HSCT or marrow involvement)
• 2. Absolute lymphocyte count ≥200 cells/μL
• 3. Hemoglobin ≥ 8 g/dL (transfusion permitted)
• 4. Platelet count ≥ 75 000/μL (≥50 000/μL for patients with marrow involvement).
• 10. Organ function as follows:
• 1. Cardiac: left ventricular ejection fraction (LVEF) ≥ 50% by Echo or radionuclide scan.
• 2. Pulmonary: oxygen saturation ≥ 92% (room air).
• 3. Renal: calculated creatinine clearance /> 30 mL/min.
• 4. Liver:
• * Total bilirubin /< 1.5 x ULN (/< 2 × upper limit of normal (ULN)) if liver involvement).
• * If no liver involvement and total bilirubin ≥1.5 x ≤ ULN, direct bilirubin /< ULN (Gilbert syndrome)
• * Aspartate aminotransferase / alanine aminotransferase /< 3 × ULN (5 x ULN if liver involvement).
• * Albumin /> 2.5 g/dL.
• 11. For females of childbearing potential (defined as /< 24 months of amenorrhea or not surgically sterile /[absence of ovaries and/or uterus/]), a negative serum pregnancy test must be documented at screening, and prior to lymphodepletion (conditioning).
• 12. For females of childbearing potential and males, a highly effective method of contraception together with a barrier method must be used from the start of lymphodepletion (conditioning) and for at least 12 months after the last dose of study agent.

Критерии исключения

• 1. Sezary syndrome. For other tumor types, if there is a suspicion of significant circulating disease at time of leukapheresis, discuss eligibility with medical monitor prior to proceeding.
• 2. Contraindication to leukapheresis.
• 3. Prior treatment with any CD5-targeted therapy.
• 4. Any evidence of the following active viral infections:
• 1. HIV infection.
• 2. Chronic hepatitis B virus (cHBV) infection with detectable viral load. Patients with cHBV, who are receiving anti-viral prophylaxis, may be enrolled if they are asymptomatic for />5 days prior to signing informed consent (ICF).
• 3. Hepatitis C (HCV) infection with detectable viral load. Patients cured of HCV may be enrolled.
• 5. Presence of any active, uncontrolled systemic bacterial, viral or fungal infection requiring intravenous (IV) anti-infectives, including clinically significant viral infection or uncontrolled viral reactivation of Epstein-Barr virus, Cytomegalovirus, Adenovirus, BK-virus, or Human herpesvirus 6. If treated with anti-infective agents, patients must be asymptomatic for />5 days prior to enrollment.
• 6. History of other cancer unless disease-free survival ≥ 2 years (cured non-melanoma skin cancer, in situ breast, non-muscle-invasive bladder or in situ cervical cancer are eligible to enter the trial without time limitations).
• 7. History of hypersensitivity reactions to products containing murine proteins.
• 8. Active CNS lymphoma.
• 9. Evidence of acute graft versus host disease (aGVHD) /> Grade 2 Mount Sinai Acute GVHD International Consortium (MAGIC) or chronic GVHD /> mild (NIH) requiring ongoing systemic steroids and/or multiagent therapy.
• 10. Patients who have received systemic immunosuppressive therapy for treatment of GVHD within 28 days of leukapheresis.
• 11. Currently requiring systemic corticosteroid therapy (10 mg/day or less of prednisone or equivalent doses of other systemic steroids are allowed for control of non-exclusionary pre-existing conditions). A 2-week washout is required prior to leukapheresis and prior to lymphodepletion for patients on /> 10 mg/day prednisone equivalent.
• 12. Patients who have received donor lymphocyte infusions within 28 days of MB-105 infusion.
• 13. Comorbidity that would impair the patient`s ability to receive or tolerate MB-105 and/or affect participation in the study:
• 1. History of cardio- or cerebrovascular disease including myocardial infarction, unstable angina, or congestive heart failure (NYHA class III-IV) within 6 months or cerebrovascular accident (CVA; stroke) within 12 months prior to informed consent.
• 2. History of central nervous system (CNS) disorder(s) such as an uncontrolled seizure disorder, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• 3. Any serious underlying medical or psychiatric condition deemed by the investigator and medical monitor to be exclusionary due to risk to the patient or to protocol compliance.
• 14. History of autoimmune disorders, including rheumatic diseases and thyroid disorders (though patients with a history of thyroid disease who have undergone successful therapy may be suitable). Exemptions for mild or limited disease may be granted after discussion between the Investigator and sponsor`s medical monitor.
• 15. Participated in active treatment on other interventional research clinical trials /< 30 days before enrollment (participation in follow-up permitted).

Описание

This is a clinical trial testing whether the addition of one of two chemotherapy agents, dasatinib or venetoclax, can improve outcomes for children and young adults with newly diagnosed T-cell acute lymphoblastic leukemia and lymphoma or mixed phenotype acute leukemia.

Primary Objective

* To evaluate if the end of induction MRD-negative rate is higher in patients with T-ALL treated with dasatinib compared to similar patients treated with 4-drug induction on AALL1231.
* To evaluate if the end of induction MRD-negative rate is higher in patients with ETP or near-ETP ALL treated with venetoclax compared to similar patients treated with 4-drug induction on AALL1231.

Secondary Objectives

* To assess the event free and overall survival of patients treated with this therapy.
* To compare grade 4 toxicities, event-free survival (EFS) and overall survival (OS) of patients treated with this therapy in induction and reinduction to toxicities of similar patients treated on TOT17.

Критерии включения

• * Enrollment on INITIALL.
• * Age 1-18.99 years at the time of enrollment on INITIALL.
• * T-Acute lymphoblastic leukemia or lymphoblastic lymphoma or mixed phenotype acute leukemia/ lymphoma
• * No prior chemotherapy excluding therapy given on or allowed by INITIALL.
• * Patient has completed no more than 3 days of chemotherapy on INITIALL.
• * Direct bilirubin ≤ 1.5x the upper limit of normal for age
• * Alanine aminotransferase (ALT) ≤ 5x the upper limit of normal for age
• * Calculated glomerular filtration rate (GFR) ≥ 50 mL/min/1.73m/^2 using the Bedside Schwartz equation OR creatinine below or equal to the maximum defined below:
• * Age: 1 to /< 2 years - Maximum serum creatinine (mg/dL): 0.6 (Male), 0.6 (Female)
• * Age: 2 to /< 6 years - Maximum serum creatinine (mg/dL): 0.8 (Male), 0.8 (Female)
• * Age: 6 to /< 10 years - Maximum serum creatinine (mg/dL): 1 (Male), 1 (Female)
• * Age: 10 to /< 13 years - Maximum serum creatinine (mg/dL): 1.2 (Male), 1.2 (Female)
• * Age: 13 to /< 16 years - - Maximum serum creatinine (mg/dL): 1.5 (Male), 1.4 (Female)
• * Age: ≥ 16 years - Maximum serum creatinine (mg/dL): 1.7 (Male), 1.4 (Female)

Критерии исключения

• * Inability or unwillingness to give informed consent/ assent as applicable.
• * Patients with /> Grade 2 neuropathy at the time of enrollment (participant with T-LLy only).
• * Documented malabsorption syndrome or any other condition that precludes receipt of oral medications.
• * Known HIV infection or active hepatitis B (defined as hepatitis B surface antigen-positive) or C (defined as hepatitis C antibody-positive).
• * Pregnant or lactating.
• * For patients of reproductive potential, unwillingness to use highly effective contraception for the duration of protocol therapy and for 90 days afterwards.
• * Receipt of a strong or moderate CYP3A4 inducer such as rifampin, carbamazepine, phenytoin, and St. John`s wort within 7 days of the start of protocol treatment.
• * Consumption of grapefruit, grapefruit products, Seville oranges, or starfruit within 3 days of the start of protocol therapy.

Описание

This study is a multi-center, global, open-label, Phase 1b/2 clinical study, and it will be conducted at multiple study sites in several countries, including Japan, Korea, and Singapore, to reveal the safety, tolerability, dose limiting toxicity (DLT), maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D), pharmacokinetics (PK), and preliminary efficacy of BCV in patients with relapsed or refractory lymphoma and to assess the efficacy and safety of Brincidofovir (SyB V-1901, BCV) in patients with relapsed or refractory Extranodal Natural Killer/T-cell Lymphoma (ENKL).

This study consists of 2 parts and will enroll a total (maximum) of 43 male and female participants who meet the eligibility criteria (Phase 1b part: Up to 18 participants /[3 to 6 participants in each of the 3 cohorts/], Phase 2 part: 25 participants).

Критерии включения

• * Patients who are histopathologically diagnosed with ENKL based on the World Health Organization (WHO) Classification of Malignant Lymphoma 5th Edition (WHO-HAEM5) (can be enrolled in the Phase 1b part and the Phase 2 part) or patients diagnosed with EBV-positive nodal T- and NK-cell lymphoma (EBV + nTNKCL), nodal T-follicular helper cell lymphoma (nTFHcL) (including angioimmunoblastic T-cell lymphoma (AITL) as defined in the WHO Classification, 4th Edition), peripheral T-cell lymphoma not otherwise specified (PTCL, NOS), anaplastic large cell lymphoma (ALCL), diffuse large B-cell lymphoma (DLBCL) (e.g., DLBCL, NOS), or adult T-Cell Leukemia Lymphoma (ATLL) (can only be enrolled in the Phase 1b part)
• * Patients with relapsed or refractory lymphoma and previously treated with systemic chemotherapy (history of multidrug chemotherapy including L-asparaginase such as SMILE therapy for ENKL is mandatory) who are ineligible for other systemic therapies
• * Patients with the following Eastern Cooperative Oncology Group (ECOG) Performance Status (PS):
• * Phase 1b part: 0-1
• * Phase 2 part: 0-2

Критерии исключения

• * Patients with another active malignant tumor requiring treatment
• * Patients with NCI-CTCAE Grade 2 or higher diarrhea (increase of 4 or more bowel movements per day compared to usual number of bowel movements) within 7 days prior to starting the first dose of BCV
• * Graft-Versus-Host Disease (GVHD) patients requiring immunosuppressive agents
• * Patients with a history of Cidofovir intolerance
• * Patients with a history of being diagnosed with cirrhosis

Описание

The researchers are doing this study to find out whether enasidenib is a safe treatment for people with angioimmunoblastic T-cell lymphoma (AITL) that has an IDH2 mutation. The researchers will look at the safety of enasidenib when it is given alone or in combination with the drug rituximab.

Критерии включения

• * Pathologically-confirmed AITL at the enrolling institution, with confirmed IDH2 mutation (by MSK ddPCR). For R/R patients, disease must have relapsed or progressed after at least one systemic therapy, diagnostic tumor samples have at least 5% tumor. i) IDH2 hotspot mutation confirmed by CAP/CLIA-certified NGS testing panel. Only cases with confirmed mutations detected />1% VAF will be eligible.
• * Age ≥18 years at time of enrollment Previous systemic anti-cancer therapy for AITL must have been discontinued at least 2 weeks or 5 half-lives (whichever is longer) prior to treatment.
• i) ii) See section 6.2 Subject Exclusion Criteria for guidelines regarding adjuvant and maintenance therapy for prior malignancy. Patients who have received localized RT as part of their immediate prior therapy may be allowed to enroll with shorter washout period after discussion with the MSKCC Principal Investigator ii) Patients who have received localized RT as part of their immediate prior therapy may be allowed to enroll with shorter washout period after discussion with the MSKCC Principal Investigator iii) Systemic corticosteroids must be tapered to 25 mg/day prednisone (or equivalent) upon start of investigational treatment iv) 4) 5) 6) 7) 8) 9) Topical steroids for treating cutaneous involvement of AITL is permitted Performance status, as assessed in the ECOG grading system, ≤2 Laboratory criteria (use of GCSF and/or blood product transfusions to reach eligibility criteria must be discussed with the MSK PI on a case-by-case basis)

Критерии исключения

• -

Описание

The primary purpose of this study is to evaluate the anti-tumor activity of TLN-254 monotherapy in participants with relapsed or refractory T-cell lymphoma.

Критерии включения

• Age:
• 1. At least 18 years of age at the time of signing the informed consent form (ICF).
• Type of Participant and Disease Characteristics:
• 2. Cohort 1: Peripheral T-cell lymphoma (PTCL) that has relapsed after, or not responded to at least one prior systemic treatment regimen. Participants with Anaplastic large cell lymphoma (ALCL) should have received prior brentuximab vedotin treatment.
• * Nodal T-follicular helper (TFH) cell lymphoma angioimmunoblastic; Follicular helper T-cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma).
• * Nodal TFH cell lymphoma, follicular type; Follicular helper T-cell lymphoma, follicular type.
• * Nodal TFH cell lymphoma, not otherwise specified (NOS); Follicular helper T-cell lymphoma, NOS.
• * PTCL, NOS.
• * Anaplastic large-cell lymphoma, Alkaline phosphatase (ALK) positive.
• * Anaplastic large-cell lymphoma, ALK negative.
• Cohort 2: Relapsed/refractory CTCL which has relapsed after, or not responded to at least two prior systemic treatments.
• * Sezary syndrome
• * Mycosis fungoides
• 3. Participant must have measurable disease at study entry.
• 4. Freshly biopsied or archival tissue available.
• Diagnostic Assessments:
• 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• 6. Adequate organ function.
• Contraception:
• 7. Participants must accept and follow the pregnancy prevention plan.

Критерии исключения

• Medical Conditions:
• 1. Participants must not have prior systemic anti-cancer treatment less than or equal to (≤) 5 half-lives or 4 weeks, allogeneic SCT≤90 days or autologous SCT ≤60 days prior to study intervention initiation.
• 2. Participants must not have any condition, including significant acute or chronic medical illness, active or uncontrolled infection, or the presence of laboratory abnormalities, that places participants at unacceptable risk if participating in this study.
• 3. Current or past history of central nervous system (CNS) involvement.
• Other Exclusions:
• * Pregnant or lactating women.
• * Unable to swallow tablets.

Описание

To evaluate the use of HyBryte, a topical photosensitizing agent, to treat patients with patch/plaque phase cutaneous T-cell lymphoma (mycosis fungoides).

Критерии включения

• * Patients must have a clinical diagnosis of cutaneous T-cell lymphoma (CTCL), Stage IA, Stage IB, or Stage IIA.
• * Patients with a minimum of three (3) evaluable, discrete lesions.
• * Patients willing to follow the clinical protocol and voluntarily give their written informed consent.
• * Female patients not pregnant or nursing and willing to undergo a pregnancy test within 30 days prior to treatment initiation.

Критерии исключения

• * History of sun hypersensitivity and photosensitive dermatoses including porphyria, systemic lupus erythematosus, Sjögren`s syndrome, xeroderma pigmentosum, polymorphous light eruptions, or radiation therapy within 30 days of enrolling.
• * History of allergy or hypersensitivity to any of the components of HyBryte.
• * A Screening ECG with a QT interval />470 ms (corrected for heart rate using the Fridericia`s formula).
• * All women of childbearing potential (WOCBP) and males with female partners who are WOCBP not willing to use effective contraception.
• * Patients receiving topical steroids or other topical treatments (eg, nitrogen mustard) on treated lesions for CTCL within 2 weeks of enrollment.
• * Patients receiving systemic steroids, psoralen UVA radiation therapy (PUVA), narrow band UVB light therapy (NB-UVB) or carmustine (BCNU) or other systemic therapies for CTCL within 4 weeks of enrollment.
• * Patients who have received electron beam irradiation within 3 months of enrollment.
• * Patients with a history of significant systemic immunosuppression.
• * Patients taking other investigational drugs or drugs of abuse within 30 days of entry into this study.
• * Patients whose condition is spontaneously improving.
• * Patients with tumor stage or erythrodermic CTCL (stages IIB-IV).
• * Patients with extensive skin disease (/>30% body surface area) who would be, in the judgement of the Principal Investigator, candidates for systemic treatment.
• * Patient has any condition that, in the judgment of the PI, is likely to interfere with participation in the study.
• * Prior participation in the current study.

Описание

This is a single-arm, open-label, single-center, phase I study. The primary objective is to evaluate the safety of CD7 Chimeric Antigen Receptor-T(CAR-T) therapy for patients with CD7-positive relapsed or refractory natural killer/T cell lymphoma, and to evaluate the pharmacokinetics of CD7 CAR-T in patients。

Критерии включения

• 1. Age 3-70
• 2. Diagnosis of r/r NK/T lymphoma.
• 3. CD7 positive expression
• 4. Bone marrow lymphoblasts ≥5% by morphologic evaluation at screening
• 5. Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min, Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST) /< 3×upper limit of normal, Total bilirubin /< 1.5×upper limit of normal or ≤1.5mg/dl
• 6. Left ventricular ejection fraction ≥ 50% .
• 7. Baseline oxygen saturation ≥ 92% on room air.
• 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• 9. The estimated survival time is more than 3 months.
• 10. Subjects or their legal guardians volunteer to participate in the study and sign the informed consent.

Критерии исключения

• 1. Subjects with concomitant genetic syndromes associated with bone marrow failure states.
• 2. Isolated extramedullary lesions
• 3. Subjects with some cardiac conditions will be excluded.
• 4. With uncontrolled active central nervous system leukemia (CNSL), cerebrospinal fluid grade Central Nervous System3(CNS3).
• 5. History of traumatic brain injury, consciousness disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic disease, which might compromise the ability of the subject to compliance with the obligations under the protocol.
• 6. History of malignancy other than non-melanoma skin cancer or carcinoma.
• 7. Primary immune deficiency.
• 8. Presence of uncontrolled infections.
• 9. Subjects with some anticancer therapy before CAR-T infusion will be excluded.
• 10. Active uncontrolled acute infections.
• 11. Known history of infection with human immunodeficiency virus (HIV); active or latent hepatitis B, hepatitis C and syphilis.
• 12. Subjects who are receiving systemic steroid therapy prior to screening.

Описание

Indolent T/NK-cell lymphomas are a heterogeneous group of lymphoproliferative diseases originating from T/NK cells, characterized by slow growth and proliferation, but currently remain incurable. For indolent T/NK-cell lymphomas that are unresponsive to first-line treatment, there are few treatment options available and the prognosis is poor. This study is an open-label, prospective clinical trial aimed at evaluating the feasibility, efficacy, and safety of PI3K inhibitors in the treatment of relapsed/refractory indolent T/NK-cell lymphomas. Patients will be treated with Golidocitnib, with an expected overall response rate of 60% for JAK1 inhibitor Golidocitnib treatment.

Критерии включения

• 1. Age ≥ 18 years, with no restrictions on gender;
• 2. Histologically confirmed relapsed/refractory (R/R) indolent T/NK-cell; lymphoma that has failed at least one systemic therapy or is intolerant to such treatment and/or currently has no effective standard treatment options;
• 3. The patient meets the criteria for appropriate therapeutic indications;
• 4. ECOG performance status of 0-2;
• 5. Adequate organ function, defined as: Total bilirubin (TBIL) ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN; Blood urea nitrogen (BUN)/Urea and creatinine (Cr) ≤ 1.5 × ULN; Left ventricular ejection fraction (LVEF) ≥ 50%; Fridericia-corrected QT interval (QTcF): /< 450 ms for males, /< 470 ms for females;
• 6. An expected survival time of at least 3 months;
• 7. Male and female subjects of childbearing potential must agree to use effective contraception throughout the study period and for 6 months after the last dose of the investigational drug;
• 8. A washout period of ≥ 4 weeks since receiving any prior antitumor therapies (including radiotherapy, chemotherapy, hormone therapy, surgery, or molecular targeted therapy) before participating in this study;
• 9. The subject has not participated in any other clinical trial within 1 month prior to enrollment;
• 10. The subject agrees to and signs the informed consent form.

Критерии исключения

• 1. Subjects who have previously used any JAK inhibitors;
• 2. Subjects with clinical conditions such as dysphagia, malabsorption, or other chronic gastrointestinal diseases that may interfere with compliance and/or absorption of the study drug;
• 3. Subjects with active viral, bacterial, or fungal infections requiring treatment (e.g., pneumonia);
• 4. Subjects with HBV or HCV infections, defined as HBsAg and/or HBcAb positivity and HBV DNA copy number ≥ the upper limit of normal (ULN), or acute or chronic active hepatitis C (HCV antibody-positive);
• 5. Subjects with a history of immunodeficiency, including those who are HIV-positive, or those with other acquired or congenital immunodeficiency diseases, a history of organ transplantation, or a history of allogeneic bone marrow or hematopoietic stem cell transplantation;
• 6. Subjects who have undergone autologous hematopoietic stem cell transplantation within 90 days prior to the first dose of study treatment;
• 7. Subjects with severe or uncontrolled cardiovascular diseases;
• 8. Subjects with severe concomitant diseases that pose a significant risk to patient safety or, in the investigator`s judgment, may interfere with the completion of the study (e.g., uncontrolled hypertension, diabetes, or thyroid disorders);
• 9. Pregnant or breastfeeding female subjects, or baseline positive pregnancy test results in women of childbearing potential;
• 10. Subjects with a history of other malignancies diagnosed or treated within the past 5 years;
• 11. Any other conditions that, in the investigator`s opinion, render the subject unsuitable for participation in the study.

Описание

This study is a prospective, phase II clinical trial with the primary objective of assessing the effectiveness of demethylating agents combined with venetoclax in the prevention of recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) of high risk T-lymphoblastic lymphoma/leukemia (T-LBL/ALL) patients.

Критерии включения

• * 1.14-55 years old, male,or female.
• * 2.Patients with allo-HSCT due to T-LBL/ALL, the donor type is not limited.
• * 3.ECOG score is 0-2 points.
• * 4.Blood routine: ANC ≥ 1.0 × 109/L, PLT ≥ 50 × 109/L.
• * 5.One of the following high-risk factors:
• * a. Age of initial diagnosis ≥ 35 years old.
• * b. Initial diagnosis of WBC ≥ 100 × 109/L.
• * c. Initial diagnosis of LDH exceeding the upper limit of normal values.
• * d. Initial diagnosis of bone marrow involvement (blast cells ≥ 5%).
• * e. Initial diagnosis of a bulky in the mediastinum (longest diameter ≥ 10cm).
• * f. ETP immunophenotype.
• * g. During the induction chemotherapy process, 2 courses did not achieve partial remission and/or 4 courses did not achieve complete remission.
• * h. Residual lesions before transplantation: Flow cytometry analysis showed that the proportion of abnormal lymphoid cells in the bone marrow was greater than 0.01%; Positive detection of minimal residual lesions in molecular biology; PET-CT scan shows that residual lesions are still active.
• * i. Based on the ELN recommendation based on adult T-ALL: gene mutations involving myeloid related genes, RAS/PI3K/AKT, JAK/STAT signaling pathway, and epigenetics, such as FLT3, NRAS/KRAS, PTEN, IL7R, JAK1, JAK3, DNMT3A, IDH1, IDH2; TP53, BCL2 mutations; t (8; 14) (q24; q11)/MYC rearrangement; t (7; 19) (q34; p13)/TCR-LYL1，TCR-MEF2C; del(5q) (q14).
• * j. High risk subgroups based on NGS definition: PI3K signaling pathway/NRAS, KRAS/TP53/IKZF1/DNTM3A/IDH1, IDH2 gene mutation with or without NOTCH1, FBXW7/PHF6/EP300 gene mutation.

Критерии исключения

• ：
• * 1.Central involvement during any course of the disease.
• * 2.Patients who have not achieved complete remission before transplantation.
• * 3.Identify those with available targeted drugs.
• * 4.For those who are resistant to BCL-2 inhibitors before transplantation, if the disease progresses during the application process, or if 3-4 courses of induction therapy containing BCL2 inhibitors do not improve.
• * 5.Individuals who are known to be allergic to demethylating drugs or venetoclax.
• * 6.Individuals with grade 2 or more degrees of active acute GVHD.
• * 7.Individuals with moderate to severe chronic GVHD.
• * 8.T-LBL/ALL relapse (flow cytometry abnormal lymphocyte cell proportion/>0.01%, WT1 positive, fusion gene positive, or extramedullary recurrence), or transplant rejection, bone marrow donor cell chimerism/<95%.
• * 9.Blood routine: ANC/<1.0 × 109/L or PLT/<50 × 109/L.
• * 10.Combined with severe organ dysfunction; The ratio of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) is more than 3 times the normal value or the normal value of direct bilirubin is more than 3 times; The endogenous creatinine clearance rate (Ccr) is less than 50mL/min or 1.5 times the normal value of blood creatinine, regardless of whether hemodialysis treatment is used.
• * 11.Merge severe active infections.
• * 12.Pregnant or lactating women.
• * 13. Accepting other investigational drugs.
• * 14.According to the researchers` assessment, the patient may have complications that could lead to other dangers.