临床试验/NCT06210750

NCT06210750撤回2 期

A Randomized Phase 2 Trial to Evaluate the Efficacy of BCL-2 Inhibitor Therapy With Chemotherapy Compared to Chemotherapy Alone in Adult Patients With Newly Diagnosed T-Cell ALL and T-Cell Lymphoblastic Lymphoma

National Cancer Institute (NCI)0 个研究点开始时间: 2024年8月9日最近更新: 2024年5月17日

适应症

干预措施

试验速览

阶段: 2 期
状态: 撤回
发起方: National Cancer Institute (NCI)
主要终点: Incidence of adverse events (Cohorts 1, 2 and 3)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

This phase II trial tests the safety and effectiveness of giving chemotherapy with or without venetoclax and/or navitoclax for the treatment of patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL). Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax and navitoclax are in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. They may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving chemotherapy with or without venetoclax and/or navitoclax may be effective treatments for patients with newly diagnosed T-ALL or T-LBL.

详细描述

PRIMARY OBJECTIVES:

I. To evaluate the safety of venetoclax + navitoclax + AALL0434 chemotherapy backbone (arm 4) before initiating randomization. (Cohort 1) II. To compare rates of undetectable measurable residual disease (MRD) at day 29 following induction therapy of AALL0434 chemotherapy (arm 1) versus: 1) venetoclax + AALL0434 chemotherapy backbone (arm 2); 2) navitoclax + AALL0434 chemotherapy backbone (arm 3) and; 3) venetoclax and navitoclax + AALL0434 chemotherapy backbone (arm 4) (3 primary comparisons). (Cohort 1) III. To evaluate the safety of AALL0434 chemotherapy backbone (without nelarabine). (Cohort 2) IV. If the AALL0434 chemotherapy backbone is found to be safe, then to evaluate the safety of the backbone + venetoclax and navitoclax. (Cohort 2) V. To estimate the percent of participants with detectable disease in the bone marrow as measured by multiparameter flow cytometry at diagnosis. (Cohort 2) VI. To estimate rates of undetectable MRD at day 29 following induction therapy within and across treatment arms in cohort 2. (Cohort 2) VII. To evaluate the safety of modified AALL0434 chemotherapy backbone (including nelarabine). (Cohort 3) VIII. If the AALL0434 chemotherapy backbone is found to be safe, then to evaluate the safety of the backbone + venetoclax and navitoclax. (Cohort 3) IX. To estimate rates of undetectable MRD at day 29 within and across treatment arms in cohort 3. (Cohort 3)

SECONDARY OBJECTIVES:

I. To estimate the response rates of complete remission (CR), complete remission with incomplete count recovery (CRi), both with and without MRD, event-free survival, relapse-free survival, and overall survival across participant cohorts and within randomized regimens in cohort 1.

II. To estimate the frequency and severity of toxicities across participant cohorts and within randomized regimens in cohort 1.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 60 Years（Adult）
性别: All
接受健康志愿者: 否

入选标准

•Participants must have newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-lineage lymphoblastic lymphoma (T-LBL) based on 2022 World Health Organization (WHO) criteria. Participants with acute leukemia of ambiguous lineage (ALAL), including mixed phenotype acute leukemia (MPAL), are not eligible for this trial
•For T-ALL, immunophenotyping of the blood or marrow lymphoblasts must be performed by flow cytometry to confirm T-cell lineage and exclude ALAL or MPAL. Appropriate lineage-specific antigens include cytoplasmic or surface CD3 for T lineage, myeloperoxidase (MPO) or monocytic antigens (CD11c, CD14, CD64, lysozyme) for myeloid lineage, and CD19, CD20, CD22, CD79a, CD10 and PAX5 for B lineage. For T-LBL, immunohistochemistry on paraffin embedded tissue alone can be used to establish the diagnosis, although flow cytometry is preferred
•NOTE: Systemic chemotherapy must begin within 72 hours of first dose of intrathecal therapy
•Collection of pretreatment blood and bone marrow specimens must be completed within 14 days prior to registration for all participants. If bone marrow is unable to be aspirated and blood blast percentage is at least 5%, additional blood should be collected as instructed in the study calendar
•Participants must not have received prior induction chemotherapy for T-ALL/LBL. Prior treatments with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids, leukapheresis to reduce peripheral blast count and prevent complications from leukocytosis, and a single dose of intrathecal cytarabine and/or methotrexate with or without steroids are permitted
•Participants must discontinue strong CYP3A4 inducers within 7 days prior to registration. Dose adjustments for CYP3A4 inhibitors/inducers during protocol therapy are defined in the protocol
•Participants must be 18-60 years old
•Participants must have Zubrod/Eastern Cooperative Oncology Group (ECOG performance status of 0-2
•Participants must have a complete medical history and physical exam within 28 days prior to registration
•Participants with extramedullary disease at diagnosis must have a CT scan with contrast of chest, neck, abdomen, pelvis, or whole body to obtain baseline values within 28 days prior to registration
•Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). Participants with history of Gilbert's disease or leukemia involving the liver must have total bilirubin ≤ 5 x institutional ULN within 7 days prior to registration
•Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) Both must be ≤ 3 × institutional ULN unless related to leukemia involving the liver
•Participants must have a serum creatinine 1.5 ≤ the ULN OR measured OR calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault Formula. This specimen must have been drawn and processed within 7 days prior to registration
•Participants must have a lumbar puncture to determine CNS involvement of ALL within 14 days prior to registration. Intrathecal cytarabine and/or methotrexate administered prior to study registration may count as the first dose of intrathecal therapy required as part of protocol therapy
•Participants must have cardiac ejection fraction >= 50% by MUGA or 2-D echocardiogram within 28 days before registration. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
•Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated
•Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
•Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated
•Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial (in the opinion of the treating physician)
•Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 24 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
•Participants with T-ALL must not have a history of seizure disorder due to nelarabine administration
•Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
•Participants must agree to have blood and bone marrow specimens submitted for MRD

排除标准

未提供

研究组 & 干预措施

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Biospecimen Collection (Procedure)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Bone Marrow Aspiration (Procedure)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Bone Marrow Biopsy (Procedure)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Calaspargase Pegol (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Computed Tomography (Procedure)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Cyclophosphamide (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Cytarabine (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Daunorubicin (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Dexamethasone (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Doxorubicin (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Echocardiography (Procedure)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Lumbar Puncture (Procedure)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Mercaptopurine (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Methotrexate (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Multigated Acquisition Scan (Procedure)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Nelarabine (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Pegaspargase (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Positron Emission Tomography (Procedure)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Thioguanine (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: Vincristine (Drug)

Arm 1 (AALL0434 regimen)

Active Comparator

See detailed description for Arm 1

干预措施: X-Ray Imaging (Procedure)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Biospecimen Collection (Procedure)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Bone Marrow Aspiration (Procedure)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Bone Marrow Biopsy (Procedure)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Lumbar Puncture (Procedure)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Calaspargase Pegol (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Computed Tomography (Procedure)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Cyclophosphamide (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Cytarabine (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Daunorubicin (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Dexamethasone (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Doxorubicin (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Echocardiography (Procedure)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Mercaptopurine (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Methotrexate (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Multigated Acquisition Scan (Procedure)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Nelarabine (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Pegaspargase (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Positron Emission Tomography (Procedure)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Thioguanine (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Venetoclax (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: Vincristine (Drug)

Arm 2 (AALL0434 regimen with venetoclax)

Experimental

See detailed description for Arm 2

干预措施: X-Ray Imaging (Procedure)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Biospecimen Collection (Procedure)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Bone Marrow Aspiration (Procedure)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Bone Marrow Biopsy (Procedure)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Calaspargase Pegol (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Computed Tomography (Procedure)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Cyclophosphamide (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Cytarabine (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Daunorubicin (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Dexamethasone (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Doxorubicin (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Echocardiography (Procedure)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Lumbar Puncture (Procedure)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Mercaptopurine (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Methotrexate (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Multigated Acquisition Scan (Procedure)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Navitoclax (Biological)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Nelarabine (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Pegaspargase (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Positron Emission Tomography (Procedure)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Thioguanine (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: Vincristine (Drug)

Arm 3 (AALL0434 regimen with navitoclax)

Experimental

See detailed description for Arm 3

干预措施: X-Ray Imaging (Procedure)