OncoTrials - мониторинг клинических исследований

Описание

A Phase 3, randomized, 2-arm, open-label, multicenter, stratified study of soquelitinib versus physician`s choice standard of care (SOC) treatment (selected single agents) in participants with relapsed/refractory (R/R) peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), follicular helper T-cell lymphomas (FHTCLs), or systemic anaplastic large-cell lymphoma (sALCL).

Критерии включения

• 1. Adult participants ≥18 years of age on the day of signing the informed consent form.
• 2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
• 3. Histologically confirmed PTCL-NOS, FHTCLs or sALCL per The International Consensus Classification of Mature Lymphoid Neoplasms.
• 4. Progressed on, be refractory to, relapsed, or intolerant to standard therapy for their cancer. At least 1 but not more than 3 prior systemic therapies.
• 5. Fluorodeoxyglucose-avid disease by positron emission tomography and measurable disease of at least 1.5 cm by computed tomography, as assessed by the site radiologist.
• 6. Life expectancy />12 weeks.
• 7. Adequate organ function as determined by:
• * Absolute neutrophil count ≥ 1.0×10/^9/L (1000/mm3) (without receiving granulocyte-colony stimulating factor)
• * Platelet count ≥ 50×10/^9/L (without transfusion)
• * Hemoglobin ≥ 9.0 g/dL, without packed red blood cell transfusion within the last 1 week of starting study drug
• * Prothrombin time international normalized ratio and partial thromboplastin time ≤1.5 × upper limit of normal (ULN), unless participant is receiving anticoagulant therapy and prothrombin time or activated partial thromboplastin time is within therapeutic range of intended use of anticoagulants
• * Calculated creatinine clearance (CrCl) according to Cockcroft-Gault formula and based on ideal body weight or 24-hour urine CrCl ≥ 50 mL/minute
• * Total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ ULN for participants with total bilirubin levels /> 1.5 × ULN. For participants with Gilbert`s disease: ≤ 3.0 mg/dL or discussion with the Medical Monitor
• * Aspartate aminotransferase and alanine transaminase ≤ 2.5 × ULN (≤ 5 × ULN for participants with liver metastases)
• * Serum albumin /> 2.5 g/dL
• * Serum calcium /< 12 mg/dL or corrected serum calcium /< ULN
• 8. Female participants of childbearing potential who are sexually active with a non-sterilized male partner must agree to use at least 1 highly effective method of contraception from the time of screening and must agree to continue using such precautions for 120 days after the last dose of study drug for participants who receive soquelitinib, or 6 months after the last dose for participants who receive either belinostat or pralatrexate.
• 9. Non-sterilized males who are sexually active with a female partner of childbearing potential must use a condom plus spermicide from Day 1 through 120 days after the last dose of study drug.

Критерии исключения

• 1. Participants who have T-cell lymphoma with active central nervous system involvement.
• 2. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study.
• 3. Any condition that confounds the ability to interpret data from the study.
• 4. Any active infection requiring IV therapy.
• 5. History of invasive prior malignancy that required systemic therapy within last 3 years.
• 6. Known to be positive for HIV, or positive test for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen /[HBsAg/]) or positive test for hepatitis C antibody.
• 7. Monoclonal antibody therapy for cancer, radiotherapy, or chemotherapy within 3 weeks and targeted therapy within 2 weeks prior to the first dose of study treatment.
• 8. History of allogeneic hematopoietic stem cell transplantation.
• 9. Candidate for hematopoietic stem cell transplantation at screening.
• 10. History of progressive disease within 6 months of autologous hematopoietic stem cell transplantation.
• 11. Females who are pregnant, lactating, or intend to become pregnant during their participation in the study, starting with the screening visit through 6 months after the last dose of study treatment.

Описание

Tazemetostat is an oral EZH2 inhibitor which has been FDA approved for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies, and for adult patients with R/R FL who have no satisfactory alternative treatment option. We propose a study to evaluate the safety of tazemetostat in relapsed / refractory peripheral T-cell lymphoma.

Критерии включения

• 1. Histologically confirmed peripheral T-cell lymphomas (PTCL) with allowed subtypes listed below as per the revised World Health Organization 2022 classification /[6/]:
• PTCL subtypes allowed
• 1. PTCL-not otherwise specified (NOS)
• 2. Nodal T-follicular helper cell lymphoma - angioimmunoblastic type, follicular type, or NOS
• 3. Anaplastic Large Cell Lymphoma (ALK+)
• 4. Anaplastic Large Cell Lymphoma (ALK-)
• 5. Enteropathy-associated T-cell lymphoma
• 6. Monomorphic epitheliotropic intestinal T-cell lymphoma
• 7. Hepatosplenic T-cell lymphoma
• 8. Subcutaneous panniculitis-like T-cell lymphoma
• 9. Adult T-cell leukemia / lymphoma - lymphomatous, acute, or unfavorable chronic subtypes
• 2. Patients must have relapsed or refractory disease.
• 1. Relapsed disease is defined when a patient progressed (/>3 months) after achieving CR with a previous treatment
• 2. Refractory disease is defined when a patient failed to achieve a CR or PR after a previous treatment
• 3. Patients received at least 1 prior therapy for PTCL.
• 4. At least one bi-dimensionally measurable nodal lesion, defined as ≥ 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as ≥ 1.0 cm in its longest diameter on fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan as defined by response criteria for PTCL
• 5. Age ≥ 18.
• 6. Patients with Hepatitis C can be included if they have completed therapy for hepatitis C with undetectable viral load.
• 7. Patients with Hepatitis B can be included if they are on suppressive therapy for hepatitis B infection and with no detectable viral load.
• 8. Patients with HIV can be included if they are on appropriate antiretroviral therapy, there is no interaction with the study drug, a CD4+ T-cell counts ≥ 350 cells/µL and no detectable viral load.
• 9. Adequate organ function as defined below unless attributed to disease involvement (Note: transfusions and growth factors allowed during screening; however, transfusion-dependency defined as requiring blood products ≥once per week not allowed):
• i. Liver function: No more than moderate hepatic impairment per NCI ODWG criteria - Total bilirubin ≤ 3X upper limit of normal (ULN), AST ≤ ULN (unless attributed to fatty liver or disease involvement).
• ii. Kidney function: CrCl /> 30ml/min using Cockroft-Gault, based on actual weight.
• iii. ANC ≥ 1,000/µL, Platelet Count ≥ 75,000/ µL, Hemoglobin ≥ 8.0 g/dl.
• 10. Left ventricular ejection fraction (LVEF) defined by multiple-gated acquisition (MUGA) scan or echocardiogram within the institutional limits of normal.
• 11. Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2.
• 12. A negative urine or serum pregnancy test is required for all women of childbearing potential within 1 week prior to enrolling on this trial and within 3 days of first dose of study drug. Note: Urine pregnancy tests that cannot be confirmed as negative require a confirmatory negative serum pregnancy test.
• Non-childbearing potential is defined as:
• * Postmenopausal: Defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, FSH measurements indicating post-menopausal status must be documented in patient`s medical history.
• * Permanently sterile: Documented permanent sterilization e.g., hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
• 13. If female of childbearing potential, subject must not be pregnant or be breastfeeding and is required to have a negative urine or serum pregnancy test within 3 days prior to the first dose of study drug. In addition, females of childbearing potential must either practice complete abstinence or agree to use two effective methods of contraception simultaneously, beginning ≥ 28 days prior to start of tazemetostat, during tazemetostat treatment, and for at least 6 months after final dose of tazemetostat. See Appendix E regarding contraception guidelines.
• 14. Male subjects must either practice complete abstinence or agree to use a latex or synthetic condom during any sexual contact with a female of childbearing potential, from first dose of tazemetostat, during study treatment including dose interruptions, and for 3 months after last dose of tazemetostat. This applies even to males who have undergone successful vasectomy with medically confirmed azoospermia.
• 15. Willing and able to participate in all required evaluations and procedures in this study protocol including receiving intravenous administration of investigational product and being admitted, when required, for at least 24 hours during investigational product administration.

Критерии исключения

• 1. Current evidence of central nervous system involvement.
• 2. Completion of an autologous hematopoietic stem cell transplantation within 3 months prior to first dose of study drug.
• 3. Prior allogeneic stem cell transplant within 6 months. The patient should not have any active GVH or should be on immune suppressive agents.
• 4. Completion of treatment with any radiotherapy, chemotherapy, antibody, immunoconjugates and/or another investigational drug ≤4 weeks (or 5 half-lives of the drug, whichever is shorter) prior to first dose of study drug. Patients may be enrolled after a minimum of 2 weeks of radiation if radiation was for palliative intent.
• 5. Prior therapy with an EZH2 inhibitor.
• 6. Inability to swallow and retain oral medications.
• 7. Pregnant women are excluded from this study.
• 8. Any active, concurrent, significant illness or disease (other underlying lymphoma) or clinically significant findings including psychiatric and behavioral problems, medical history and/or physical examination findings that would preclude the patient from participation in the study such as:
• i. Active infection requiring systemic therapy ≤10 days before the first dose of study drug; ii. Unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association /[NYHA/] II, III, IV;), myocardial infarction ≤6 months prior to first study drug, uncontrolled cardiac arrhythmia e.g., atrial fibrillation/flutter, cerebrovascular accidents ≤6 months before first dose of study drug; iii. Any severe or uncontrolled other disease or condition which might increase the risk associated with study participation.
• 9. Vaccination with live, attenuated vaccines within 28 days prior to the first dose of study medication.
• 10. Receiving systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents). The use of inhaled corticosteroids is permitted.
• 11. Corticosteroids ≥ 10 mg of prednisone within the last 7 days.
• 12. Has had a solid organ transplant within the last 3 years. Note: Patients who have had a solid organ transplant />3 years ago are eligible if there are no signs/symptoms of graft versus host disease (GvHD) and off immunosuppressive medications as per above.
• 13. Any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN).
• 14. Any prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL).
• 15. Patients with the following subtypes of lymphoma:
• i. T-cell prolymphocytic leukemia ii. T-large granular lymphocytic leukemia iii. NK-large granular lymphocytic leukemia iv. Aggressive NK-cell leukemia v. Breast implant-associated anaplastic large-cell lymphoma
• 16. Any other malignancy known to be active, with the exception of i. Cervical carcinoma of Stage 1B or less ii. Non-invasive basal cell or squamous cell skin carcinoma iii. Non-invasive, superficial bladder cancer iv. Prostate cancer with a current PSA level /< 0.1 ng/mL v. Any curable or localized cancer with a CR of /> 2 years` duration.
• 17. Any malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat.
• 18. Major surgery within 4 weeks before the first dose of study intervention. Note: Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrolment.

Описание

The goal of this clinical trial is to evaluate the efficacy and safety of Pembrolizumab in combination with Olaparib in participants with relapsed/refractory Peripheral T-cell Lymphoma (PTCL).

The study mainly aims to evaluate:

* objective response rate (ORR) as per Cheson response criteria assessed by the independent central review
* overall survival and progression-free survival
* adverse events by CTCAE version 5.0

The administration of Pembrolizumab and Olaparib to participants will occur on Day 1 of each 3-week dosing cycle and will continue until disease progression or unacceptable toxicity, up to 35 cycles. Treatment with Olaparib will proceed continuously from Day 1 of Cycle 1, in 3-week dosing cycles in parallel with Pembrolizumab, up to 35 cycles, unless specific withdrawal/discontinuation criteria are met. After the end of treatment, each subject will be followed for 30 days for adverse event (AE) monitoring (serious AEs /[SAEs/] will be collected for 90 days after the end of treatment or 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier).

Критерии включения

• 1. Male/female participants who are at least 21 years of age on the day of signing informed consent with histologically or cytologically-confirmed diagnosis of peripheral T-cell lymphoma (PTCL), including angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma of T-follicular helper cell derivation (PTCL-TFH), anaplastic large cell lymphoma (ALCL), NK/T-cell lymphoma (NKTCL), gamma-delta T cell lymphoma (GDTL), enteropathy associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), subcutaneous panniculitis like T-cell lymphoma, and PTCL, not otherwise specified (PTCL-NOS) will be enrolled in this study.
• 2. Male participants:
• A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least the time needed to eliminate the study intervention (180 days for Olaparib; no requirement for pembrolizumab) after the last dose of study treatment and refrain from donating sperm during this period.
• 3. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least the time needed to eliminate the study intervention (180 days for Olaparib; 120 days for pembrolizumab) after the last dose of study treatment.
• 4. Participants must have progressed on treatment with at least one prior systemic anti-cancer therapy including investigational agents. These may include an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
• 1. Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• 2. Has demonstrated disease progression after anti-PD-1/L1 as defined by Cheson response criteria. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression (as defined in 4.c).
• 3. Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• * Progressive disease is determined according to Cheson response criteria.
• * This determination is made by the investigator. Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression.
• Progression on other systemic anti-cancer therapy including investigational agents is defined by radiographic disease progression based on Cheson response criteria.
• 5. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• 6. Have measurable disease based on Cheson criteria. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• 7. Archival tumor tissue sample or newly obtained /[core, incisional or excisional/] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• 8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
• 9. Have adequate organ function as defined in the following. Specimens must be collected within 10 days prior to the start of study intervention.
• * Absolute neutrophil count (ANC)≥500/μL
• * Platelets ≥25 000/μL
• * Hemoglobin ≥8 g/dL
• * Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels />1.5 × institutional ULN
• * Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels />1.5 × ULN
• * AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
• * International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• * Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• 10. Hepatitis B and C screening tests are required:
• * Hepatitis B positive subjects
• * Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrolment.
• * Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
• * Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
• * Participants must have completed curative anti-viral therapy at least 4 weeks prior to enrolment.
• 11. Participant has a life expectancy of at least 3 months

Критерии исключения

• 1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• 2. Has received prior systemic investigational agents within 4 weeks (or shorter interval for kinase inhibitors or other short half-life drugs, per investigator discretion) or has used an investigational device within 4 weeks prior to treatment.
• 3. Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.
• 4. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• 5. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• 6. Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder that have undergone potentially curative therapy are not excluded.
• 7. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• 8. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• 9. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid)
• 10. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• 11. Has an active infection requiring systemic therapy.
• 12. Has a known history of Human Immunodeficiency Virus (HIV) infection.
• 13. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
• Note: HIV, Hepatitis B and C screening tests are required.
• 14. Has not adequately recovered from major surgery or has ongoing surgical complications.
• 15. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant`s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• 16. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• 17. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of trial treatment.
• 18. Has had an allogenic tissue/solid organ transplant.

Описание

Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may be the potential to develop the corresponding CAR-T cells to treat patients whose tumors express those markers. In this study, investigators will evaluate the safety and efficacy of Sequential CAR-T Cells Targeting CD5/CD7 in patients with patients with relapsed or refractory T-ALL/LBL/ETP-ALL. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, disease status after treatment will also be evaluated.

Критерии включения

• * Signed written informed consent; Patients volunteer to participate in the clinical trial;
• * Diagnosis is mainly based on the World Health Organization (WHO) 2008;
• * Complete remission cannot be achieved after induction therapy; recurrence occurs after completion remission; the burden of leukemic blasts in the peripheral blood or bone marrow is greater than 5%;
• * Leukemic blast cells express CD7/CD5 (CD7 OR CD5 positive by flow cytometry or immunohistochemistry ≥70%);
• * The expected survival period is greater than 12 weeks;
• * ECOG score ≤2;
• * Age 2-60 years old;
• * HGB≥70g/L (can be transfused);
• * Total bilirubin does not exceed 3 times the upper limit of normal value, and AST and ALT do not exceed 5 times the upper limit of normal value.

Критерии исключения

• * Patients declining to consent for treatment
• * Prior solid organ transplantation
• * One of the following cardiac issues: atrial fibrillation; myocardial infarction within the past 12 months; prolonged QT syndrome or secondary QT prolongation; clinically significant pericardial effusion; cardiac insufficiency NYHA (New York Heart Association) III or IV;
• * History of severe pulmonary dysfunction diseases;
• * Severe infection or persistent infection cannot be effectively controlled;
• * Severe autoimmune disease or congenital immunodeficiency;
• * Active hepatitis;
• * Human immunodeficiency virus (HIV) infection;
• * Clinically significant viral infections, or uncontrollable viral reactivation, including EBV (Epstein-Barr virus).

Описание

This is an open label, multicenter, phase 1/2 dose evaluation and cohort expansion study evaluating the safety and efficacy of CTX131 in subjects with Relapsed/Refractory Hematologic Malignancies

Критерии включения

• 1. ≥18 years of age
• 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (ECOG status of 2 will be permitted for subjects with AML)
• 3. Diagnosed with r/r T Cell Lymphoma (TCL), B Cell Lymphoma (BCL), or Acute Myeloid Leukemia (AML) T cell lymphoma, including Stage ≥IIB Mycosis fungoides (MF)/ Sézary syndrome (SS) after at least 2 prior systemic therapies Peripheral T cell lymphoma (PTCL) after at least 1 prior line of therapy (PTCL-note otherwise specified (NOS), PTCL-T follicular helper (TFH), Angioimmunoblastic T cell lymphoma (AITL), Adult T cell leukemia/lymphoma (ATLL) of leukemic, lymphomatous, and chronic unfavorable subtypes), (ALK)- ALCL after at least 1 prior line of therapy, ALK+ Anaplastic large cell lymphoma (ALCL) after at least 2 prior lines of therapy
• B cell lymphoma, including Diffuse large B cell lymphoma (DLBCL)-NOS, transformed marginal zone lymphoma(MZL), transformed FL, high-grade BCL with MYC and BCL2 and/or BCL6 rearrangements, Follicular lymphoma (FL) grade 3b, after at least 2 prior lines of therapy including an anti- CD20 monoclonal antibody and an anthracycline containing regimen Mantle cell lymphoma (MCL) after up to 5 prior lines of therapy which must include an anthracycline- or bendamustine-containing regimen, an anti- CD20 monoclonal antibody, and a BTK inhibitor
• Acute myeloid leukemia or AML/MDS per ELN criteria 2022 after at least 1 prior line of AML therapy. APL, BCR-ABL positive leukemia, and AML secondary to prior therapy or history of genetic syndrome associated with BM failure are excluded.
• 4. Adequate renal, liver, cardiac and pulmonary organ function
• 5. Females of childbearing potential and male subjects must agree to use an acceptable, highly effective method of contraception (as specified in the protocol) from enrollment through at least 12 months after last CTX131 infusion

Критерии исключения

• 1. Prior treatment with anti-CD70 targeting agents
• 2. Active CNS manifestation of underlying disease
• 3. History or presence of clinically relevant CNS pathology such as seizure, stroke, severe brain injury, cerebellar disease, myelopathy, history of posterior reversible encephalopathy syndrome with prior therapy, or another condition that in opinion of investigator may increase CAR T-related toxicities
• 4. Uncontrolled bacterial, viral, or fungal infection
• 5. Positive for HIV, or active hepatitis B virus or hepatitis C virus infection.
• 6. Concurrent systemic treatment with an anticancer biologic (e.g., monoclonal antibody) within 30 days prior to CTX131 infusion or with a non-biological anticancer drug within 14 days prior to CTX131 infusion. Mogamulizumab treatment is prohibited 50 days prior to CTX131 infusion.
• 7. Diagnosis with another invasive malignancy in the last 5 years with the exception of non- melanoma skin cancer and malignancies deemed by the investigator and medical monitor to be of low likelihood for recurrence
• 8. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy.
• 9. Prior solid organ or allogeneic BM transplantation, except for AML cohorts if at least 3 months since allogeneic HSCT, not receiving immunosuppressive therapy or donor lymphocyte infusion post SCT in the 2 weeks prior to lymphodepletion, and have no clinically active GvHD
• 10. Treatment with CD19-targeting CAR-T within 6 months prior to CTX131 infusion

Описание

This study is a single-center, single-arm, prospective phase II clinical trial that evaluates the efficacy and safety of allogeneic peripheral blood stem cell transplantation in the treatment of high-risk peripheral T-cells lymphoma patients achieved complete response (CR) or partial response (PR). Conventional conditioning regimen is adopted while the reduced-intensity conditioning regimens will be preferred. Donor hematopoietic stem cell infusion is performed on day 0. All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year after transplantation. Positron emission tomography with 2-deoxy-2-/[fluorine-18/]fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) imaging will be performed every 6 months after transplantation. If disease relapse is suspected during the follow-up period, bone marrow and relapse site examinations will be conducted at any time. The primary study endpoints are the 1-year and 2-year progression-free survival (PFS) rates post-transplant. Secondary study endpoints include the incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant, cumulative relapse rates at 1 year and 2 years post-transplant, 1-year and 2-year overall survival (OS), graft-versus-host disease-free, relapse-free survival (GRFS), non-relapse mortality (NRM), cumulative incidence of chronic GVHD, and the incidence of Cytomegalovirus （CMV）and Epstein-Barr virus（EBV）reactivation within 1 year.

Критерии включения

• 1. Age between 18 and less than 70 years, regardless of gender 2. Peripheral T-cell lymphoma (PTCL) was diagnosed according to the 2016 WHO criteria and met any of the following criteria:
• 1. High risk: IPI（International Prognostic Index） score ≥ 3 or aaIPI（age-adjusted International Prognostic Index） score ≥ 2 ( aaIPI is suitable for patients younger than 60 years old).
• 2. Patients who achieved complete response (CR) or partial response (PR) after first-line chemotherapy (PET-CT or CT examination was performed according to the patient `s economic conditions） 3.Patients must have a suitable hematopoietic stem cell donor:
• Related donors must have at least 5/10 matches for HLA-A, -B, -C, -DQB1, and - DRB1.
• Unrelated donors must have at least 8/10 matches for HLA-A, -B, -C, -DQB1, and -DRB1.
• 4.Hematopoietic cell transplantation comorbidity index (HCT-CI) score ≤ 2. 5.ECOG (Eastern Cooperative Oncology Group) performance status: 0-2. 6.Adequate liver, kidney, and cardiopulmonary function, meeting the following requirements:
• 1. Serum creatinine ≤ 1.5x ULN (the upper limit of normal).
• 2. Cardiac function: Ejection fraction ≥ 50%.
• 3. Baseline oxygen saturation /> 92%.
• 4. Total bilirubin ≤ 2.0 x ULN; ALT and AST ≤ 2.0 x ULN，AKP ≤ 2.0 x ULN
• 5. Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40% and FEV1 (Forced Expiratory Volume in 1 second) ≥ 50%.
• 7.Patients must have the ability to understand and be willing to participate in this study and sign an informed consent form.
• Exclusion Criteria:
• 1. PTCL patients did not meet the criteria of high-risk.
• 2. PTCL ALK + patients with CR after first-line treatment.
• 3. History of malignancies other than lymphoid tumors within the 5 years prior to screening, except for adequately treated in situ cervical cancer, basal cell carcinoma, squamous cell carcinoma of the skin, and curatively treated localized prostate cancer or ductal carcinoma in situ
• 4. ECOG ≥ 3.
• 5. HCT-CI score ≥ 3.
• 6. Any unstable systemic diseases, including but not limited to unstable angina, recent cerebrovascular accidents or transient ischemic attacks within the 3 months prior to screening, myocardial infarction within the 3 months prior to screening, congestive heart failure (New York Heart Association /[NYHA/] class ≥ III), severe arrhythmias requiring drug treatment after pacemaker implantation, significant liver, kidney, or metabolic diseases, and pulmonary arterial hypertension.
• 7. Active, uncontrolled infections, including those associated with hemodynamic instability, new or worsening infection symptoms or signs, new infectious lesions on imaging, or persistent unexplained fever without signs or symptoms of infection.
• 8. HIV-infected individuals.
• 9. Active hepatitis B (HBV) or active hepatitis C (HCV) requiring antiviral therapy.
• 10. History of autoimmune diseases
• 11. Pregnant or breastfeeding women.
• 12. Fertile males and females unwilling to use contraception during the treatment period and for 12 months after treatment.

Критерии исключения

Описание

This is an open-label, prospective and exploratory clinical study to evaluate the efficacy and safety of JAK inhibitor SHR-0302 in combination with EZH2 inhibitor SHR-2554 in patients with R/R PTCL. The study plans to enroll approximately 25 patients. 6-12 patients will receive SHR-0302 monotherapy and SHR-0302+SHR-2554 combination therapy in the safety run-in phase. According to the safety observed, the investigators discuss and decide to select a dose group to explore the efficacy and safety. 13 patients may be enrolled in the expansion phase.

Критерии включения

• * Males or females aged 18-70 years (inclusive);
• * Histologically confirmed peripheral T-cell lymphoma;
• * Disease status defined as relapsed or refractory after />=1 prior systemic treatment lines;
• * Have measurable lesions;
• * ECOG performance status must be 0 or 1 and has not deteriorated in the past 2 weeks;
• * Life expectancy ≥12 weeks;
• * Adequate bone marrow reserve and organ system function reserve;
• * Participants should be able and willing to comply with the study protocol requirement

Критерии исключения

• * Received anti-tumor treatment within 28 days prior to the first dose of the study drug; received Chinese medicine treatment with anti-tumor effect within 14 days before the first dose of the study drug; received steroid hormones within 7 days prior to the first dose of study drug administration;
• * Underwent major surgery within 4 weeks prior to the first dose of study treatment；
• * Severe cardiovascular disease;
• * Cerebrovascular accident or transient ischemic attack within 6 months prior to enrollment;
• * Significant impairment of lung function;
• * Active infections;
• * Unexplained fever /> 38.5°C during screening period or on the first day of medication;
• * Pregnant;
• * Known alcohol or drug abuse;
• * Subjects are currently receiving known moderately potent or potent CYP inducers/inhibitors or P-glycoprotein (P-gp) inhibitors;
• * History of hypersensitivity to the investigational drug or its excipients;
• * In the judgment of the investigator, objective conditions make the subject unable to complete the planned study or the subject has other factors, concomitant diseases, combined treatment or abnormal laboratory examination that may lead to the forced termination of the study.

Описание

Extranodal NK/T-cell lymphoma is a rare and highly aggressive subtype of non-Hodgkin lymphoma. While the overall survival rates have improved for early-stage ENKTL patients, the prognosis for those with advanced disease remains poor, and there is currently no standard treatment. PD-1/PD-L1 inhibitors have demonstrated significant efficacy in various cancers, and recent studies have shown promising results in extranodal NK/T-cell lymphoma as well. Although PD-1 antibodies have exhibited efficacy in relapsed or refractory patients, their effectiveness when combined with chemotherapy as a first-line treatment remains unclear. This study aims to evaluate the efficacy and safety of sintilimab combined with chemotherapy in a randomized controlled trial for newly diagnosed advanced extranodal NK/T-cell lymphoma patients, while also exploring potential biomarkers that may predict treatment outcomes, offering new therapeutic options for extranodal NK/T-cell lymphoma patients.

Критерии включения

• 1. Pathologically diagnosed with ENKTL.
• 2. Advanced stage.
• 3. Has at least one measurable or assessable lesion.
• 4. Age /> 18 years, no gender restrictions, with an expected survival of more than 3 months.
• 5. Willing to participate in the clinical study; fully informed and has signed a written informed consent form.
• 6. Adequate organ and bone marrow function.

Критерии исключения

• 1. Aggressive NK-cell leukemia.
• 2. Central nervous system involvement.
• 3. Patients with significant dysfunction of vital organs.
• 4. History of allergy to the investigational drug, similar drugs, or excipients.
• 5. Less than 6 weeks since major organ surgery (excluding surgery for biopsy purposes).
• 6. Pregnant or breastfeeding women, and women of childbearing potential who are unwilling to use contraception.
• 7. Active infection, excluding fever related to tumor-associated B symptoms.
• 8. Known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS).

Описание

This study is a single-center, single-arm, prospective phase II clinical trial that evaluates the efficacy and safety of an reduced-intensity conditioning (RIC) regimen with thiotepa combined with busulfan, fludarabine, and cytarabine for allogeneic hematopoietic stem cell transplantation in the treatment of relapse and refratory peripheral T-cells lymphoma. The conditioning regimen includes thiotepa at a dose of 5mg/kg/d at d -7 (1 day), fludarabine at 30mg/m2/d from d -6 to d -2 (5 days), cytarabine at 1g/m2/d from d -6 to d -2 (5 days), and busulfan at 3.2mg/kg/d from d -4 to d -3 (2 days). Conditioning begins on day -7, and donor hematopoietic stem cell infusion is performed on day 0. All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year after transplantation. FDG-PET/CT imaging will be adopted every 6 months after transplantation. If disease relapse is suspected during the follow-up period, bone marrow and relapse site examinations will be conducted at any time. The primary study endpoints are the 1-year and 2-year progression-free survival (PFS) rates post-transplant. Secondary study endpoints include the incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant, cumulative relapse rates at 1 year and 2 years post-transplant, 1-year and 2-year overall survival (OS), graft-versus-host disease-free, relapse-free survival (GRFS), non-relapse mortality (NRM), cumulative incidence of chronic GVHD, and the incidence of Cytomegalovirus （CMV）and Epstein-Barr virus（EBV）reactivation within 1 year.

Критерии включения

• * Age between 18 and less than 70 years, regardless of gender
• * Peripheral T-cell lymphoma (PTCL) was diagnosed according to the 2016 WHO criteria and met any of the following criteria: Relapse: Except ALK+ anaplastic large cell lymphoma （ALCL), CR was achieved by standard chemotherapy but disease progressed，and relapse after hematopoietic stem cell transplantation;Refractory: Except ALK+ anaplastic large cell lymphoma （ALCL), the tumor shrank /< 50% or progressive disease after 4 courses of standard chemotherapy, or not achieve CR after 6 courses of standard chemotherapy;Not suitable for or refusing autologous hematopoietic stem cell transplantation.
• * Patients must have a suitable hematopoietic stem cell donor:Related donors must have at least 5/10 matches for HLA-A, -B, -C, -DQB1, and - DRB1;Unrelated donors must have at least 8/10 matches for HLA-A, -B, -C, -DQB1, and -DRB1
• * Hematopoietic cell transplantation comorbidity index (HCT-CI) score ≤ 2
• * ECOG (Eastern Cooperative Oncology Group) performance status: 0-2
• * Adequate liver, kidney, and cardiopulmonary function, meeting the following requirements:Serum creatinine ≤ 1.5x ULN (the upper limit of normal);Cardiac function: Ejection fraction ≥ 50%;Baseline oxygen saturation /> 92%;Total bilirubin ≤ 2.0 x ULN; ALT and AST ≤ 2.0 x ULN，AKP ≤ 2.0 x ULN;Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40% and FEV1 (Forced Expiratory Volume in 1 second) ≥ 50%
• * Patients must have the ability to understand and be willing to participate in this study and sign an informed consent form

Критерии исключения

• * PTCL patients did not meet the criteria of relapse / refractory.
• * Refuse to adopt allegeneic hematopoietic stem cell transplantation.
• * History of malignancies other than lymphoid tumors within the 5 years prior to screening, except for adequately treated in situ cervical cancer, basal cell carcinoma, squamous cell carcinoma of the skin, and curatively treated localized prostate cancer or ductal carcinoma in situ
• * ECOG ≥ 3.
• * HCT-CI score ≥ 3.
• * Any unstable systemic diseases, including but not limited to unstable angina, recent cerebrovascular accidents or transient ischemic attacks within the 3 months prior to screening, myocardial infarction within the 3 months prior to screening, congestive heart failure (New York Heart Association /[NYHA/] class ≥ III), severe arrhythmias requiring drug treatment after pacemaker implantation, significant liver, kidney, or metabolic diseases, and pulmonary arterial hypertension.
• * Active, uncontrolled infections, including those associated with hemodynamic instability, new or worsening infection symptoms or signs, new infectious lesions on imaging, or persistent unexplained fever without signs or symptoms of infection.
• * HIV-infected individuals.
• * Active hepatitis B (HBV) or active hepatitis C (HCV) requiring antiviral therapy.
• * History of autoimmune diseases
• * Pregnant or breastfeeding women.
• * Fertile males and females unwilling to use contraception during the treatment period and for 12 months after treatment.

Описание

Cutaneous T-cell lymphoma (CTCL) is a group of diseases resulting from clonal hyperplasia of memory T cells in the skin. The increasing incidence and high treatment costs have posed significant challenges to public health and the economy. Current treatment guidelines only provide partial control, leading to varying remission times and recurrence rates. This study aims to use molecular subtyping and immunohistochemistry to guide treatment selection for CTCL patients, aiming to prolong clinical benefit, improve treatment safety, and reduce economic burden.

Критерии включения

• * Signed informed consent;
• * Patients with CTCL who do not respond well to targeted skin therapy (topical corticosteroids, nitrogen mustard, or phototherapy) in the early stage (stage I-IIA) and advanced stage (stage IIB-IV);
• * Age 18-75 years;
• * Expected survival time greater than 3 months (follow-up for the historical control group was greater than 3 months)

Критерии исключения

• * Received other anti-tumor therapy other than skin-targeted therapy (phototherapy, topical hormones or nitrogen mustard) within the past 1 month prior to enrollment;
• * Patients with 2 or more types of primary cutaneous T-cell lymphoma at the same time;
• * Combined with other malignant tumors, still receiving anti-tumor therapy;
• * Has any other active disease that may increase the risk of protocol therapy or impair the patient/'s ability to receive protocol therapy, including but not limited to:
• * Comorbid epilepsy;
• * Comorbid autoimmune diseases;
• * Combined with hepatic decompensation;
• * Patients with renal insufficiency and creatinine clearance /< 50ml/min;
• * Have an uncontrollable medical condition, including but not limited to:
• * Ongoing or active infection;
• * Clinically significant healing or non-healing wounds;
• * Symptomatic congestive heart failure, unstable angina, clinically significant arrhythmias;
• * Significant lung disease (e.g., shortness of breath at rest or light activity, or need for supplemental oxygen for any reason);
• * Diseases/conditions that affect study compliance, such as infectious diseases or psychiatric illnesses/social situations, that are uncontrollable;
• * Pregnant (or intending to become pregnant within 2 years) or lactating females;
• * Concomitant participation in interventional clinical trials of other clinical trial drugs, except for questionnaire surveys or observational studies;
• * Any situation in which the programme is not in compliance;
• * Other conditions that in the opinion of the investigator are not suitable for participation in this study.

Описание

This is a prospective, single arm, multicenter study to evaluate the safety and efficacy of CMOEP in patients with untreated peripheral T-cell lymphoma.

Критерии включения

• * 1.Subjects fully understand and voluntarily participate in this study and sign informed consent.
• 2. Age ≥18, ≤70years(for 65-70 years old, researchers need to comprehensively evaluate the physical fitness and tolerance of patients), no gender limitation.
• 3. Expected survival ≥ 3 months. 4.Histologically confirmed diagnosis of Peripheral T-cell lymphoma： 1) Peripheral T-cell lymphoma unspecified (ptcl-NOS) 2) Angioimmunoblastic T-cell lymphoma (AITL) 3) Anaplastic large T-cell lymphoma (ALCL), ALK+ 4) Anaplastic large T-cell lymphoma (ALCL), ALK- 5) Other subtypes of PTCL that the investigator think can be included in the group.
• 5.No previous treatment for PTCL, including chemotherapy, targeted therapy, immunotherapy, local radiotherapy for lymphoma (except for local radiotherapy to alleviate tumor related symptoms), surgical treatment.
• 6.Subjects must have at least one evaluable or measurable lesion per lugano2014 criteria: for lymph node lesions, the length and diameter should be />1.5cm; For non-lymph node lesions, the length and diameter should be />1.0cm.
• 7.Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1. 8.The following baseline laboratory criteria are required: Absolute neutrophil count (ANC) ≥1.5×10/^9/L, Platelet count (PLT) ≥75×10/^9/L, Hemoglobin(HB)≥ 90 g/L(Restriction may be relaxed in patients with bone marrow involvement, Absolute neutrophil count (ANC) ≥1.0×10/^9/L, Platelet count (PLT) ≥50×10/^9/L, Hemoglobin(HB)≥ 75g/L).
• 9.Total Serum creatinine (Scr) ≤1.5X upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5X ULN(For patients with liver invasion ≤5X ULN), bilirubin (TBIL)≤1.5X ULN(For patients with liver invasion ≤3X ULN ).

Критерии исключения

• * 1.Subjects with a history of prior antitumor therapy. 2.Hypersensitivity to any study drug or its components. 3.Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.) 4.Heart function and disease meet one of the following conditions:1）Long QTc syndrome or QTc interval />480 ms;2）Complete left bundle branch block, grade II or III atrioventricular block;3）Serious and uncontrolled arrhythmias requiring drug treatment;4）New York Heart Association grade ≥ II;5）Cardiac ejection fraction (LVEF)/<50%;6）A history of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically serious pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment.
• 5.Hepatitis B and hepatitis C active infection (defined as hepatitis B virus surface antigen positive and hepatitis B virus DNA higher than 1x10/^3 copy/mL; hepatitis C virus RNA high than 1x10/^3 copy/mL).
• 6.Human immunodeficiency virus (HIV) infection (HIV antibody positive). 7.Patients with other malignant tumors, except for effectively controlled non melanoma skin basal cell carcinoma, breast/cervical carcinoma in situ and other tumor during the past 5 years.
• 8.Patients with primary or secondary central nervous system (CNS) lymphoma or history of CNS lymphoma.
• 9.Pregnant and lactating women and patients of childbearing age who are unwilling to take contraceptive measures.
• 10.Unsuitable subjects for this study determined by the investigator.

Описание

This clinical trial is studying the safety and potential anti-tumor activity of an investigational drug called ARV-393 in patients diagnosed with advanced Relapsed/Refractory non-Hodgkin`s lymphoma to determine if ARV-393 may be a possible treatment option.

ARV-393 is thought to work by breaking down a protein present in many types of non-Hodgkins lymphomas, which may prevent, slow or stop tumor growth. This is the first time ARV-393 will be used by people. The investigational drug will be given as an oral tablet.

Критерии включения

• * Eligible participants aged ≥18 years.
• * Have relapsed/refractory mature B-cell non-Hodgkin lymphoma (NHL) and ≥2 prior systemic therapies, or histologically confirmed AITL that has recurred or progressed following institutional standard-of-care therapy.
• * Participants must also have ≥1 measurable lesion at study entry
• * Eastern Cooperative Oncology Group performance status of 0 or 1,
• * Freshly biopsied or archival tumor tissue available,
• * Participants with adequate organ function,
• * Participants must accept and follow pregnancy prevention guidance.

Критерии исключения

• * No prior allogeneic stem cell transplant or solid organ transplantation, Autologous stem cell transplant, must not have occurred ≤100 days, previous CAR T-cell therapy ≤60 days, radiotherapy ≤ 2 weeks, systemic anticancer treatment ≤ 5 half-lives or 4 weeks, prior to ARV-393 treatment initiation.
• * Participants must not have significant acute or chronic medical illness, including hypereosinophilic syndrome, active interstitial lung disease or pneumonitis, active or uncontrolled infection, or the presence of laboratory abnormalities, that places participants at unacceptable risk if participating in this study.
• * Participants with an inability to comply with listed prohibited treatments.

Описание

This is a multicenter prospective single arm phase II study. The purpose of this study is to evaluate the safety and efficiency of azacytidine combined with CAOLD Regimen in the treatment of relapsed/refractory peripheral t-cell lymphomas.

Критерии включения

• Patients must satisfy all following criteria to be enrolled in the study:
• * Pathologically confirmed angioimmunoblastic T-cell lymphoma according World Health Organization (WHO) classification;
• * Patient is ≥ 18 years of age at the time of signing the informed consent form (ICF).
• * Patient must understand and voluntarily sign an ICF prior to any study-specific assessments/procedures being conducted;
• * Patient is willing and able to adhere to the study visit schedule and other protocol requirements;
• * Relapsed (after partial or complete response) or refractory AITL after at least one line of systemic therapy (there is no mandatory resting period after the previous treatment as long as the biochemistry and hematology labs meet the inclusion criteria as below.)
• * Meet the following lab criteria:
• * Absolute Neutrophil Count (ANC) ≥ 1,5 x 10/^9/L (≥ 1 x 10/^9/L if bone marrow (BM) involvement by lymphoma)
• * Platelet ≥ 75 x 10/^9/L (≥ 50 x 10/^9/L if BM involvement by lymphoma)
• * Hemoglobin ≥ 8 g/dL.
• * Anticipated life expectancy at least 3 months

Критерии исключения

• * Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment;
• * Any instability of systemic disease, including but not limited to severe cardiac, liver, kidney, or metabolic disease need therapy;
• * Pregnant or lactating women