T Acute Lymphoblastic LeukemiaPhase 2NCT06210750

Adding Targeted Drugs to Usual Chemotherapy for Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LBL)

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with T Acute Lymphoblastic Leukemia and T Lymphoblastic Lymphoma, run by National Cancer Institute (NCI).

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 years
Conditions the study is for: T Acute Lymphoblastic Leukemia, T Lymphoblastic Lymphoma
What is being tested?: Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: No sites listed yet
Study dates: 9 Aug 2024to 22 Sep 2026
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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

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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

Who cannot join

None listed.

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

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:

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.

III. Within cohorts 1-3, to evaluate the association of CR, CRi, event-free survival, relapse-free survival, and overall survival with the T-cell immunologic subtype of early T-cell precursor (ETP) lymphoblastic leukemia, defined as CD3+, CD7+, CD8-, CD1a-, and one or more myeloid/stem cell markers CD34, CD117, HLA-DR, CD13, CD33, CD11b, and CD65, but negative for myeloperoxidase (MPO).

IV. Within cohorts 1-3, to evaluate the association of endpoints (CR, CRi, event-free survival, relapse-free survival, and overall survival) with pretreatment characteristics (including age, gender, white blood cell count, central nervous system [CNS] leukemia at diagnosis, immunophenotype, karyotype).

Across cohorts 1-3 where laboratory data is available (laboratory evaluation is not mandated in the study), to evaluate serum asparaginase activity levels at day 8 and day 15 of Induction, at day 19 and day 26 of consolidation, and day 6 and 13 of interim maintenance courses, of reduced doses peg-asparaginase in participants age > 30 years and/or participants with at least one of the following risk factors for toxicity: body mass index (BMI) > 30, history of liver disease, history of diabetes mellitus type 2. To compare asparaginase activity levels between the different arms of cohort 1.

VI. Across cohorts 1-3, to estimate the frequency and severity of toxicities associated with reduced doses of peg-asparaginase in participants age > 30 years and/or in participants with at least one of risk factors for toxicity as noted above.

TRANSLATIONAL MEDICINE PRIMARY OBJECTIVE:

Across all cohorts, to estimate rates of MRD (day 29) with centrally evaluated flow cytometry.

TRANSLATIONAL MEDICINE SECONDARY OBJECTIVES:

Across all cohorts, to estimate rates of MRD (day 78 for cohorts 1 \& 3, day 57 for cohort 2) with centrally evaluated flow cytometry.

II. Within and across cohorts 1-3, to estimate the percentage of participants with ETP and non-ETP immunophenotype.

III. Within and across cohorts 1-3, to evaluate the association of CR/CRi, event-free survival, relapse-free survival, and overall survival with ETP and non-ETP immunophenotype.

BANKING OBJECTIVE:

Across cohorts 1-3, to bank specimens for future correlative studies.

OUTLINE:

SAFETY PHASE: Patients in Cohort 1 are assigned to Arm 4. Patients in Cohort 2 are assigned to Arm 5 or Arm 6. Patients in Cohort 3 are assigned to Arm 7 or Arm 8.

RANDOMIZED PHASE: Patients in Cohort 1 are randomized to Arms 1, 2, 3, or 4.

ARM 1:

INDUCTION: Patients receive cytarabine intrathecally (IT) on day 1, vincristine intravenously (IV) and daunorubicin IV on days 1, 8, 15 and 22, dexamethasone orally (PO) twice per day (BID) on days 1-7 and 15-21, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on day 4, and methotrexate IT on days 8 and 29 (days 15 and 22 for patients with central nervous system [CNS 3] disease). Treatment continues for one 4-week cycle (weeks 1-4) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments.

CONSOLIDATION: Patients receive nelarabine IV on days 1-5 and 43- 47, cyclophosphamide IV on days 8 and 50, cytarabine IV or subcutaneously (SC) on days 8-11, 15-18, 50-53 and 57-60, mercaptopurine PO on days 8-21 and 50-63, vincristine IV on days 22, 29, 64, and 71, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 22 and 64 and methotrexate IT on days 15, 22, 57 and 64 (NOTE: Patients with CNS 3 disease omit methotrexate on day 22). Treatment continues for one 11-week cycle (weeks 6-16) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments. Patients who are MRD negative proceed, patients who are MRD positive are removed from the study.

INTERIM MAINTENANCE: Patients receive methotrexate IV and vincristine IV on days 1, 11, 21, 31 and 41, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 2 and 22 and methotrexate IT on days 1 and 31. Treatment continues for one 8-week cycle (weeks 17-24) in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION: Patients receive dexamethasone PO BID on days 1-7, and 15-21, doxorubicin IV on days 1, 8 and 15, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 4 and 50, nelarabine IV on days 29-33, cyclophosphamide IV on day 36, cytarabine IV or SC on days 36-39 and 43-46, thioguanine PO on days 36-49, vincristine IV on days 1, 8, 15, and 50 and methotrexate IT on days 1, 36, and 43. Treatment continues for one 9-week cycle (weeks 25-33) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive vincristine IV on days 1 and 57 of each cycle, dexamethasone PO BID on days 1-5, and 57-61 of each cycle, mercaptopurine PO on days 1-28 and 36-84 of each cycle, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78 of each cycle, methotrexate IT on day 1 of each cycle, and nelarabine IV on days 29-33 of cycles 1-3. Cycles repeat every 84 days for a total of 2 years from the start of Interim Maintenance in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or mitigated acquisition scan (MUGA), computed tomography (CT), positron emission tomography (PET), bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 2:

INDUCTION: Patients receive cytarabine IT on day 1, venetoclax PO on days 1-14, vincristine IV and daunorubicin IV on days 1,8,15 and 22, dexamethasone PO BID on days 1-7 and 15-21, peg-L-asparaginase IV on day 4 and methotrexate IT on days 8 and 29 (days 15 and 22 for patients with CNS 3 disease). Treatment continues for one 4-week cycle (weeks 1-4) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments.

CONSOLIDATION: Patients receive nelarabine IV on days 1-5 and 43 -47, cyclophosphamide IV on days 8 and 50, cytarabine IV on days 8-11, 15-18, 50-53 and 57-60, mercaptopurine PO on days 8-21 and 50-63, vincristine IV on days 22, 29, 64, and 71, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 22 and 64, methotrexate IT on days 15, 22, 57 and 64 (NOTE: Patients with CNS 3 disease omit methotrexate on day 22), and venetoclax PO on days 8-21. Treatment continues for one 11-week cycle (weeks 6-16) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments. Patients who are MRD negative proceed, patients who are MRD positive are removed from the study.

DELAYED INTENSIFICATION: Patients receive dexamethasone PO BID on days 1-7, and 15-21, doxorubicin IV on days 1, 8 and 15, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 4 and 50, nelarabine IV on days 29-33, cyclophosphamide IV on day 36, cytarabine IV on days 36-39 and 43-46, thioguanine PO on days 36-49, vincristine IV on days 1, 8, 15, and 50 and methotrexate IT on days 1, 36, and 43. Treatment continues for one 9-week cycle (weeks 25-33) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive vincristine IV on days 1 and 57 of each cycle, dexamethasone PO BID on days 1-5, and 57-61 of each cycle, mercaptopurine PO on days 1-28 and 36-84, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78 of each cycle, methotrexate IT on day 1 of each cycle, and nelarabine IV on days 29-33 of cycles 1-3. Cycles repeat every 12 weeks (84 days) for a total of 2 years from the start of Interim Maintenance in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 3:

INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV and daunorubicin IV on days 1, 8, 15 and 22, dexamethasone PO BID on days 1-7 and 15-21, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on day 4, navitoclax PO on days 1-14 and methotrexate IT on day 8 and 29 (days 15 and 22 for patients with CNS 3 disease). Treatment continues for one 4-week cycle (weeks 1-4) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments.

CONSOLIDATION: Patients receive nelarabine IV on days 1-5 and 43 -47, cyclophosphamide IV on days 8 and 50, cytarabine IV on days 8-11, 15-18, 50-53 and 57-60, mercaptopurine PO on days 8-21 and 50-63, vincristine IV on days 22, 29, 64, and 71, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 22 and 64, navitoclax PO on days 8-21 and methotrexate IT on days 15, 22, 57 and 64 (NOTE: Patients with CNS 3 disease omit methotrexate on day 22). Treatment continues for one 11-week cycle (weeks 6-16) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments. Patients who are MRD negative proceed, patients who are MRD positive are removed from the study.

DELAYED INTENSIFICATION: Patients receive dexamethasone PO BID on days 1-7, and 15-21, doxorubicin IV on days 1, 8 and 15, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 4 and 50, nelarabine IV on days 29-33, cyclophosphamide IV on day 36, cytarabine IV on days 36-39 and 43-46, thioguanine PO on days 36-49, vincristine IV on days 1, 8, 15, and 50 and methotrexate IT on days 1, 36, and 43. Treatment continues for one 9-week cycle (weeks 25-33) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive vincristine IV on days 1 and 57 of each cycle, dexamethasone PO BID on days 1-5, and 57-61 of each cycle, mercaptopurine PO on days 1-28 and 36-84 of each cycle, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78 of each cycle, methotrexate IT on day 1 of each cycle, and nelarabine IV on days 29-33 of cycles 1-3. Cycles repeat every 12 weeks (84 days) for a total of 2 years from the start of Interim Maintenance in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 4:

INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV and daunorubicin IV on days 1, 8, 15 and 22, dexamethasone PO BID on days 1-7 and 15-21, peg-L-asparaginase and calaspargase pegol-MKNL IV on day 4, venetoclax PO and navitoclax PO on days 1-14 and methotrexate IT on day 8 and 29 (days 15 and 22 for patients with CNS 3 disease). Treatment continues for one 4-week cycle (weeks 1-4) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments.

CONSOLIDATION: Patients receive nelarabine IV on days 1-5 and 43 -47, cyclophosphamide IV on days 8 and 50, cytarabine IV on days 8-11, 15-18, 50-53 and 57-60, mercaptopurine PO on days 8-21 and 50-63, vincristine IV on days 22, 29, 64, and 71, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 22 and 64, navitoclax PO and venetoclax PO on days 8-21 and methotrexate IT on days 15, 22, 57 and 64 (NOTE: Patients with CNS 3 disease omit methotrexate on day 22). Treatment continues for one 11-week cycle (weeks 6-16) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments. Patients who are MRD negative proceed, patients who are MRD positive are removed from the study.

DELAYED INTENSIFICATION: Patients receive dexamethasone PO BID on days 1-7, and 15-21, doxorubicin IV on days 1, 8 and 15, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 4 and 50, nelarabine IV on days 29-33, cyclophosphamide IV on day 36, cytarabine IV on days 36-39 and 43-46, thioguanine PO on days 36-49, vincristine IV on days 1, 8, 15, and 50 and methotrexate IT on days 1, 36, and 43. Treatment continues for one 9-week cycle (weeks 25-33) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive vincristine IV on days 1 and 57 of each cycle, dexamethasone PO BID on days 1-5, and 57-61 of each cycle, mercaptopurine PO on days 1-28 and 36-84 of each cycle, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78 of each cycle, methotrexate IT on day 1 of each cycle, and nelarabine IV on days 29-33 of cycles 1-3. Cycles repeat every 12 weeks (84 days) for a total of 2 years from the start of Interim Maintenance in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 5:

INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV and daunorubicin IV on days 1, 8, 15 and 22, dexamethasone PO BID on days 1-7 and 15-21, peg-L-asparaginase and calaspargase pegol-MKNL IV on day 4 and methotrexate IT on day 8 and 29 (days 15 and 22 for patients with CNS 3 disease). Treatment continues for one 4-week cycle (weeks 1-4) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments.

CONSOLIDATION: Patients receive cyclophosphamide IV on days 1 and 29, cytarabine IV or SC on days 1-4, 8-11, 29-33, and 36-39, mercaptopurine PO on days 1-14 and 29-42, vincristine IV on days 15, 22, 43, and 50, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 15 and 43, and methotrexate IT on days 1, 8, 15 and 22 (NOTE: Patients with CNS 3 disease omit methotrexate on days 15 and 22). Treatment continues for one 8-week cycle (weeks 6-13) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments. Patients who are MRD negative proceed, patients who are MRD positive are removed from the study.

INTERIM MAINTENANCE: Patients receive methotrexate IV and vincristine IV on days 1, 11, 21, 31 and 41, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 2 and 22 and methotrexate IT on days 1 and 31. Treatment continues for one 8-week cycle (weeks 14-21) in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION: Patients receive dexamethasone PO BID on days 1-7and 15-21, doxorubicin IV on days 1, 8 and 15, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 4 and 43, cyclophosphamide IV on day 29, cytarabine IV or SC on days 29-32 and 36-39, thioguanine PO on days 29-42, vincristine IV on days 1, 8, 15, 43 and 50, and methotrexate IT on days 1, 29, and 36. Treatment continues for one 9-week cycle (weeks 22-30) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive vincristine IV on days 1, 29 and 57 of each cycle, dexamethasone PO BID on days 1-5, 29-33, and 57-61 of each cycle, mercaptopurine PO on days 1-84 of each cycle, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78 of each cycle, and methotrexate IT on day 1 of each cycle. Cycles repeat every 12 weeks (84 days) for a total of 2 years from the start of Interim Maintenance in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 6:

CONSOLIDATION: Patients receive cyclophosphamide IV on days 1 and 29, cytarabine IV on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14 and 29-42, vincristine IV on days 15, 22, 43 and 50, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 15 and 43, navitoclax PO and venetoclax PO on days 1-14 and methotrexate IT on days 1, 8, 15 and 22. Treatment continues for one 8-week cycle (weeks 6-13) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments. Patients who are MRD negative proceed, patients who are MRD positive are removed from the study.

INTERIM MAINTENANCE: Patients receive methotrexate IV and vincristine IV on days 1, 11, 21, 31 and 41, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 2 and 22 and methotrexate IT on days 1 and 31. Treatment continues for one 8-week cycle (weeks 14-21) in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION: Patients receive dexamethasone PO BID on days 1-7, and 15-21, doxorubicin IV on days 1, 8 and 15, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 4 and 43, cyclophosphamide IV on day 29, cytarabine IV on days 29-32, and 36-39, thioguanine PO on days 29-42, vincristine IV on days 1, 8, 15, 43 and 50 and methotrexate IT on days 1, 29, and 36. Treatment continues for one 9-week cycle (weeks 22-30) in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 7:

INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV and daunorubicin IV on days 1, 8, 15 and 22, dexamethasone PO BID on days 1-7, peg-L-asparaginase IV on day 15, and methotrexate IT on day 8 and 29 (days 15 and 22 for patients with CNS 3 disease). Treatment continues for one 4-week cycle (weeks 1-4) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments.

CONSOLIDATION: Patients receive nelarabine IV on days 1-5 and 43-47, cyclophosphamide IV on days 8 and 50, cytarabine IV or SC on days 8-11, 15-18, 50-53, and 57-60, mercaptopurine PO on days 8-21, and 50-63, vincristine IV on days 22, 29, 64, and 71, peg-L-asparaginase IV on days 22 and 64, and methotrexate IT on days 15, 22, 57 and 64 (NOTE: Patients with CNS 3 disease omit methotrexate on day 22). Treatment continues for one 11-week cycle (weeks 6-16) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments. Patients who are MRD negative proceed, patients who are MRD positive are removed from the study.

INTERIM MAINTENANCE: Patients receive methotrexate IV and vincristine IV on days 1, 11, 21, 31 and 41, peg-L-asparaginase IV on days 2 and 22 and methotrexate IT on days 1 and 31. Treatment continues for one 8-week cycle (weeks 17-24) in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION: Patients receive dexamethasone PO BID on days 1-7, doxorubicin IV on days 1, 8 and 15, peg-L-asparaginase IV, on days 4 and 50, nelarabine IV on days 29-33, cyclophosphamide IV on day 36, cytarabine IV or SC on days 36-39, and 43-46, thioguanine PO on days 36-49, vincristine IV on days 1, 8, 15, and 50 and methotrexate IT on days 1, 36, and 43. Treatment continues for one 9-week cycle (weeks 25-33) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive vincristine IV on days 1 and 57 of each cycle, dexamethasone PO BID on days 1-5, and 57-61 of each cycle, mercaptopurine PO on days 1-28 and 36-84 of each cycle, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78 of each cycle, methotrexate IT on day 1 of each cycle, and nelarabine IV on days 29-33 of cycles 1-3. Cycles repeat every 12-weeks (84 days) for a total of 2 years from the start of Interim Maintenance in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 8:

INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV and daunorubicin IV on days 1, 8, 15 and 22, dexamethasone PO BID on days 1-7, peg-L-asparaginase on day 15, venetoclax PO and navitoclax PO in days 1-14, and methotrexate IT on day 8 and 29 (days 15 and 22 for patients with CNS 3 disease). Treatment continues for one 4-week cycle (weeks 1-4) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments.

CONSOLIDATION: Patients receive nelarabine IV on days 1-5 and 43-47, cyclophosphamide IV on days 8 and 50, cytarabine IV on days 8-11, 15-18, 50-53, and 57-60, mercaptopurine PO on days 8-21, and 50-63, vincristine IV on days 22, 29, 64, and 71, peg-L-asparaginase IV on days 22 and 64, venetoclax PO and navitoclax PO on days 8-21, and methotrexate IT on days 15, 22, 57 and 64 (NOTE: Patients with CNS 3 disease omit methotrexate on day 22). Treatment continues for one 11-week cycle (weeks 6-16) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments. Patients who are MRD negative proceed, patients who are MRD positive are removed from the study.

MAINTENANCE: Patients receive vincristine IV on days 1 and 57 of each cycle, dexamethasone PO BID on days 1-5, and 57-61 of each cycle, mercaptopurine PO on days 1-28 and 36-84 of each cycle, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78 of each cycle, methotrexate IT on day 1 of each cycle, and nelarabine IV on days 29-33 of cycles 1-3. Cycles repeat every 84 days for a total of 2 years from the start of interim maintenance in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

After completion of study treatment, patients are followed up periodically for up to 10 years after registration.

Conditions: T Acute Lymphoblastic Leukemia, T Lymphoblastic Lymphoma
Being tested: Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Calaspargase Pegol, Computed Tomography
Medical subject headings: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow aspiration
Bone Marrow BiopsyProcedure or surgery
Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow
Undergo bone marrow biopsy
Calaspargase PegolDrug
Also called Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl), Asparlas, Calaspargase Pegol-mknl, EZN-2285
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518
Given IV
CytarabineDrug
Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
Given IT, IV or SC
DaunorubicinDrug
Also called Daunomycin, Daunorrubicina, DNR, Leukaemomycin C
Given IV
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO
DoxorubicinDrug
Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin
Given IV
EchocardiographyProcedure or surgery
Also called EC
Undergo echocardiography
Lumbar PunctureProcedure or surgery
Also called LP, Spinal Tap
Undergo lumbar puncture
MercaptopurineDrug
Also called 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine
Given PO
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IT
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA scan
NavitoclaxBiological
Also called A-855071.0, ABT-263, BcI-2 Family Protein Inhibitor ABT-263
Given PO
NelarabineDrug
Also called 2-Amino-6-methoxypurine arabinoside, 506U78, Arranon, Compound 506U78
Given IV
PegaspargaseDrug
Also called L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-Asparaginase
Given IV
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET scan
ThioguanineDrug
Also called 2-Amino 6MP, 2-Amino-1,7-dihydro-6H-purine-6-thione, 2-Amino-6-mercaptopurine, 2-Amino-6-purinethiol
Given PO
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
VincristineDrug
Also called LCR, Leurocristine, VCR, Vincrystine
Given IV
X-Ray ImagingProcedure or surgery
Also called Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs
Undergo X-ray

Study groups in NCT06210750
Study group	Role	What they receive
Arm 1 (AALL0434 regimen)	Active comparator	See detailed description for Arm 1 Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Vincristine; Procedure: X-Ray Imaging
Arm 2 (AALL0434 regimen with venetoclax)	Experimental	See detailed description for Arm 2 Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine; Procedure: X-Ray Imaging
Arm 3 (AALL0434 regimen with navitoclax)	Experimental	See detailed description for Arm 3 Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Biological: Navitoclax; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Vincristine; Procedure: X-Ray Imaging
Arm 4 (AALL0434 regimen with venetoclax and navitoclax)	Experimental	See detailed description for Arm 4 Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Biological: Navitoclax; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine; Procedure: X-Ray Imaging
Arm 5 (AALL0434 [no nelarabine])	Active comparator	See detailed description for Arm 5 Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Vincristine; Procedure: X-Ray Imaging
Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax)	Experimental	See detailed description for Arm 6 Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Biological: Navitoclax; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine; Procedure: X-Ray Imaging
Arm 7 (AALL0434 regimen)	Active comparator	See detailed description for Arm 7 Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Vincristine
Arm 8 (Remission induction with venetoclax and navitoclax)	Experimental	See detailed description for Arm 8 Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Biological: Navitoclax; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine; Procedure: X-Ray Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of adverse events (Cohorts 1, 2 and 3)
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events will be used to determine severity of toxicity.
Measured: Up to 10 years
Undetectable minimal residual disease (MRD) (Cohort 1)
There will be three primary analyses, each comparing an experimental arm with the shared control arm using Fisher's exact test with a one-sided alpha of 10%. All eligible randomized participants will be used in the efficacy comparison.
Measured: At day 29 following induction
Percent of participants with detectable disease in the bone marrow (Cohort 2)
Binomial estimates will be reported along with exact 95% confidence intervals.
Measured: At diagnosis and at days 29 and 57
Undetectable MRD (Cohorts 1 and 3)
Binomial estimates will be reported along with exact 95% confidence intervals.
Measured: At days 29 and 78

Secondary outcomes (8)

Rate of complete remission (CR)
Response rates in each arm and cohort will be calculated and presented with exact binomial 95% confidence intervals.
Measured: End of consolidation therapy
Rate of complete remission with incomplete count recovery (CRi) with and without MRD
Response rates in each arm and cohort will be calculated and presented with exact binomial 95% confidence intervals.
Measured: End of consolidation therapy
Event free survival
Will be estimated using the method of Kaplan-Meier; randomized arms within Cohort 1 will be compared using the stratified log rank test.
Measured: From the date of initial registration on study until the first of the following events: death from any cause, relapse from MRD-negative remission, or completion of protocol therapy without documentation of MRD-negative remission, up to 10 years
Relapse free survival
Will be estimated using the method of Kaplan-Meier; randomized arms within Cohort 1 will be compared using the stratified log rank test.
Measured: From the date the participant first achieves CR or CRi until relapse from CR/CRi or death from any cause, up to 10 years
Overall survival
Will be estimated using the method of Kaplan-Meier; randomized arms within Cohort 1 will be compared using the stratified log rank test.
Measured: From the day of registration to death from any cause, up to 10 years
Incidence of adverse events
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events will be used to determine severity of toxicity.
Measured: Up to 10 years
Serum asparaginase activity levels
Of patients with reduced doses Peg-asparaginase in participants age > 30 years and/or participants with at least one of the following risk factors for toxicity: Body mass index (BMI) > 30, history of liver disease, history of diabetes mellitus type 2.
Measured: At day 8 and day 15 of induction, day 19 and 26 of consolidation and day 6 and 13 of interim maintenance
Incidence of adverse events associated with reduced doses of Peg-asparaginase
Participants age >30 years and/or in participants with at least one of risk factors for toxicity.
Measured: Up to 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Aug 202422 Sep 2026

First posted18 Jan 2024
Study start9 Aug 2024 (estimated)
Primary completion22 Sep 2026 (estimated)
Study completion22 Sep 2026 (estimated)

Why it stopped: Other - Protocol moved to Disapproved

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for T Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06210750
Sponsor's protocol ID: NCI-2023-09521
Other IDs: NCI-2023-09521, S2306, S2306, U10CA180888
Status last verified: May 2024
First submitted: 17 Jan 2024
Last updated: 17 May 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: "NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Recruiting
A Multicenter Study to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-Cell Recovery to Guide Management Following Chimeric Antigen Receptor T-cell (CART) Induced Remission in Children and Young Adults With B Lineage Acute Lymph...
B-All, Acute Lymphoblastic Leukemia
Active, not recruitingEarly Phase 1
Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma
B-ALL, DLBCL
Active, not recruitingPhase 2
Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Relapsed/Refractory Peripheral T-Cell Lymphoma, Adult T Cell Leukemia/Lymphoma
RecruitingPhase 1
A Phase I Dose Finding Study of MB-CART2219.1
Lymphoma, CLL

All T Acute Lymphoblastic Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT06210750
Acronym / sponsor ID: NCI-2023-09521
Conditions: T Acute Lymphoblastic Leukemia, T Lymphoblastic Lymphoma
Phase: Phase 2
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Other - Protocol moved to Disapproved
Enrolment: 0 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 9 Aug 2024 (estimated)
Primary completion: 22 Sep 2026 (estimated)
Study completion: 22 Sep 2026 (estimated)
First posted: 18 Jan 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

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:

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.

Across cohorts 1-3 where laboratory data is available (laboratory evaluation is not mandated in the study), to evaluate serum asparaginase activity levels at day 8 and day 15 of Induction, at day 19 and day 26 of consolidation, and day 6 and 13 of interim maintenance courses, of reduced doses peg-asparaginase in participants age > 30 years and/or participants with at least one of the following risk factors for toxicity: body mass index (BMI) > 30, history of liver disease, history of diabetes mellitus type 2. To compare asparaginase activity levels between the different arms of cohort 1.

TRANSLATIONAL MEDICINE PRIMARY OBJECTIVE:

Across all cohorts, to estimate rates of MRD (day 29) with centrally evaluated flow cytometry.

TRANSLATIONAL MEDICINE SECONDARY OBJECTIVES:

Across all cohorts, to estimate rates of MRD (day 78 for cohorts 1 \& 3, day 57 for cohort 2) with centrally evaluated flow cytometry.

II. Within and across cohorts 1-3, to estimate the percentage of participants with ETP and non-ETP immunophenotype.

III. Within and across cohorts 1-3, to evaluate the association of CR/CRi, event-free survival, relapse-free survival, and overall survival with ETP and non-ETP immunophenotype.

BANKING OBJECTIVE:

Across cohorts 1-3, to bank specimens for future correlative studies.

OUTLINE:

SAFETY PHASE: Patients in Cohort 1 are assigned to Arm 4. Patients in Cohort 2 are assigned to Arm 5 or Arm 6. Patients in Cohort 3 are assigned to Arm 7 or Arm 8.

RANDOMIZED PHASE: Patients in Cohort 1 are randomized to Arms 1, 2, 3, or 4.

ARM 1:

ARM 2:

DELAYED INTENSIFICATION: Patients receive dexamethasone PO BID on days 1-7, and 15-21, doxorubicin IV on days 1, 8 and 15, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 4 and 50, nelarabine IV on days 29-33, cyclophosphamide IV on day 36, cytarabine IV on days 36-39 and 43-46, thioguanine PO on days 36-49, vincristine IV on days 1, 8, 15, and 50 and methotrexate IT on days 1, 36, and 43. Treatment continues for one 9-week cycle (weeks 25-33) in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 3:

CONSOLIDATION: Patients receive nelarabine IV on days 1-5 and 43 -47, cyclophosphamide IV on days 8 and 50, cytarabine IV on days 8-11, 15-18, 50-53 and 57-60, mercaptopurine PO on days 8-21 and 50-63, vincristine IV on days 22, 29, 64, and 71, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 22 and 64, navitoclax PO on days 8-21 and methotrexate IT on days 15, 22, 57 and 64 (NOTE: Patients with CNS 3 disease omit methotrexate on day 22). Treatment continues for one 11-week cycle (weeks 6-16) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments. Patients who are MRD negative proceed, patients who are MRD positive are removed from the study.

DELAYED INTENSIFICATION: Patients receive dexamethasone PO BID on days 1-7, and 15-21, doxorubicin IV on days 1, 8 and 15, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 4 and 50, nelarabine IV on days 29-33, cyclophosphamide IV on day 36, cytarabine IV on days 36-39 and 43-46, thioguanine PO on days 36-49, vincristine IV on days 1, 8, 15, and 50 and methotrexate IT on days 1, 36, and 43. Treatment continues for one 9-week cycle (weeks 25-33) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive vincristine IV on days 1 and 57 of each cycle, dexamethasone PO BID on days 1-5, and 57-61 of each cycle, mercaptopurine PO on days 1-28 and 36-84 of each cycle, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78 of each cycle, methotrexate IT on day 1 of each cycle, and nelarabine IV on days 29-33 of cycles 1-3. Cycles repeat every 12 weeks (84 days) for a total of 2 years from the start of Interim Maintenance in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 4:

CONSOLIDATION: Patients receive nelarabine IV on days 1-5 and 43 -47, cyclophosphamide IV on days 8 and 50, cytarabine IV on days 8-11, 15-18, 50-53 and 57-60, mercaptopurine PO on days 8-21 and 50-63, vincristine IV on days 22, 29, 64, and 71, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 22 and 64, navitoclax PO and venetoclax PO on days 8-21 and methotrexate IT on days 15, 22, 57 and 64 (NOTE: Patients with CNS 3 disease omit methotrexate on day 22). Treatment continues for one 11-week cycle (weeks 6-16) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments. Patients who are MRD negative proceed, patients who are MRD positive are removed from the study.

DELAYED INTENSIFICATION: Patients receive dexamethasone PO BID on days 1-7, and 15-21, doxorubicin IV on days 1, 8 and 15, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 4 and 50, nelarabine IV on days 29-33, cyclophosphamide IV on day 36, cytarabine IV on days 36-39 and 43-46, thioguanine PO on days 36-49, vincristine IV on days 1, 8, 15, and 50 and methotrexate IT on days 1, 36, and 43. Treatment continues for one 9-week cycle (weeks 25-33) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive vincristine IV on days 1 and 57 of each cycle, dexamethasone PO BID on days 1-5, and 57-61 of each cycle, mercaptopurine PO on days 1-28 and 36-84 of each cycle, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78 of each cycle, methotrexate IT on day 1 of each cycle, and nelarabine IV on days 29-33 of cycles 1-3. Cycles repeat every 12 weeks (84 days) for a total of 2 years from the start of Interim Maintenance in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 5:

INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV and daunorubicin IV on days 1, 8, 15 and 22, dexamethasone PO BID on days 1-7 and 15-21, peg-L-asparaginase and calaspargase pegol-MKNL IV on day 4 and methotrexate IT on day 8 and 29 (days 15 and 22 for patients with CNS 3 disease). Treatment continues for one 4-week cycle (weeks 1-4) in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessments.

INTERIM MAINTENANCE: Patients receive methotrexate IV and vincristine IV on days 1, 11, 21, 31 and 41, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 2 and 22 and methotrexate IT on days 1 and 31. Treatment continues for one 8-week cycle (weeks 14-21) in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 6:

INTERIM MAINTENANCE: Patients receive methotrexate IV and vincristine IV on days 1, 11, 21, 31 and 41, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 2 and 22 and methotrexate IT on days 1 and 31. Treatment continues for one 8-week cycle (weeks 14-21) in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION: Patients receive dexamethasone PO BID on days 1-7, and 15-21, doxorubicin IV on days 1, 8 and 15, peg-L-asparaginase IV and calaspargase pegol-MKNL IV on days 4 and 43, cyclophosphamide IV on day 29, cytarabine IV on days 29-32, and 36-39, thioguanine PO on days 29-42, vincristine IV on days 1, 8, 15, 43 and 50 and methotrexate IT on days 1, 29, and 36. Treatment continues for one 9-week cycle (weeks 22-30) in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 7:

MAINTENANCE: Patients receive vincristine IV on days 1 and 57 of each cycle, dexamethasone PO BID on days 1-5, and 57-61 of each cycle, mercaptopurine PO on days 1-28 and 36-84 of each cycle, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78 of each cycle, methotrexate IT on day 1 of each cycle, and nelarabine IV on days 29-33 of cycles 1-3. Cycles repeat every 12-weeks (84 days) for a total of 2 years from the start of Interim Maintenance in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

ARM 8:

MAINTENANCE: Patients receive vincristine IV on days 1 and 57 of each cycle, dexamethasone PO BID on days 1-5, and 57-61 of each cycle, mercaptopurine PO on days 1-28 and 36-84 of each cycle, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78 of each cycle, methotrexate IT on day 1 of each cycle, and nelarabine IV on days 29-33 of cycles 1-3. Cycles repeat every 84 days for a total of 2 years from the start of interim maintenance in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray and EKG at screening and echocardiogram or MUGA, CT, PET, bone marrow aspiration, bone marrow biopsy, lumbar puncture and blood sample collection throughout the study.

After completion of study treatment, patients are followed up periodically for up to 10 years after registration.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 8

Arm	Type	Receives
Arm 1 (AALL0434 regimen)	Active comparator	Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Drug: Calaspargase Pegol, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Procedure: Echocardiography, Procedure: Lumbar Puncture, Drug: Mercaptopurine, Drug: Methotrexate, Procedure: Multigated Acquisition Scan, Drug: Nelarabine, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Thioguanine, Drug: Vincristine, Procedure: X-Ray ImagingSee detailed description for Arm 1
Arm 2 (AALL0434 regimen with venetoclax)	Experimental	Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Drug: Calaspargase Pegol, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Procedure: Echocardiography, Procedure: Lumbar Puncture, Drug: Mercaptopurine, Drug: Methotrexate, Procedure: Multigated Acquisition Scan, Drug: Nelarabine, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Thioguanine, Drug: Venetoclax, Drug: Vincristine, Procedure: X-Ray ImagingSee detailed description for Arm 2
Arm 3 (AALL0434 regimen with navitoclax)	Experimental	Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Drug: Calaspargase Pegol, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Procedure: Echocardiography, Procedure: Lumbar Puncture, Drug: Mercaptopurine, Drug: Methotrexate, Procedure: Multigated Acquisition Scan, Biological: Navitoclax, Drug: Nelarabine, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Thioguanine, Drug: Vincristine, Procedure: X-Ray ImagingSee detailed description for Arm 3
Arm 4 (AALL0434 regimen with venetoclax and navitoclax)	Experimental	Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Drug: Calaspargase Pegol, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Procedure: Echocardiography, Procedure: Lumbar Puncture, Drug: Mercaptopurine, Drug: Methotrexate, Procedure: Multigated Acquisition Scan, Biological: Navitoclax, Drug: Nelarabine, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Thioguanine, Drug: Venetoclax, Drug: Vincristine, Procedure: X-Ray ImagingSee detailed description for Arm 4
Arm 5 (AALL0434 [no nelarabine])	Active comparator	Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Drug: Calaspargase Pegol, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Procedure: Echocardiography, Procedure: Lumbar Puncture, Drug: Mercaptopurine, Drug: Methotrexate, Procedure: Multigated Acquisition Scan, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Thioguanine, Drug: Vincristine, Procedure: X-Ray ImagingSee detailed description for Arm 5
Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax)	Experimental	Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Drug: Calaspargase Pegol, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Procedure: Echocardiography, Procedure: Lumbar Puncture, Drug: Mercaptopurine, Drug: Methotrexate, Procedure: Multigated Acquisition Scan, Biological: Navitoclax, Drug: Nelarabine, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Thioguanine, Drug: Venetoclax, Drug: Vincristine, Procedure: X-Ray ImagingSee detailed description for Arm 6
Arm 7 (AALL0434 regimen)	Active comparator	Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Drug: Calaspargase Pegol, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Procedure: Echocardiography, Procedure: Lumbar Puncture, Drug: Mercaptopurine, Drug: Methotrexate, Procedure: Multigated Acquisition Scan, Drug: Nelarabine, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Thioguanine, Drug: VincristineSee detailed description for Arm 7
Arm 8 (Remission induction with venetoclax and navitoclax)	Experimental	Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Drug: Calaspargase Pegol, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Procedure: Echocardiography, Procedure: Lumbar Puncture, Drug: Mercaptopurine, Drug: Methotrexate, Procedure: Multigated Acquisition Scan, Biological: Navitoclax, Drug: Nelarabine, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Thioguanine, Drug: Venetoclax, Drug: Vincristine, Procedure: X-Ray ImagingSee detailed description for Arm 8

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (23 listed)

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

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo blood sample collection	Procedure or surgery	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
Bone Marrow AspirationUndergo bone marrow aspiration	Procedure or surgery	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
Bone Marrow BiopsyAlso: Biopsy of Bone Marrow, Biopsy, Bone MarrowUndergo bone marrow biopsy	Procedure or surgery	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
Calaspargase PegolAlso: Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl), Asparlas, Calaspargase Pegol-mknl, EZN-2285Given IV	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT	Procedure or surgery	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518Given IV	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
CytarabineAlso: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinoneGiven IT, IV or SC	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
DaunorubicinAlso: Daunomycin, Daunorrubicina, DNR, Leukaemomycin CGiven IV	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
DoxorubicinAlso: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, HydroxyldaunorubicinGiven IV	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
EchocardiographyAlso: ECUndergo echocardiography	Procedure or surgery	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
Lumbar PunctureAlso: LP, Spinal TapUndergo lumbar puncture	Procedure or surgery	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
MercaptopurineAlso: 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 ThiopurineGiven PO	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
MethotrexateAlso: Abitrexate, Alpha-Methopterin, Amethopterin, BrimexateGiven IT	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
Multigated Acquisition ScanAlso: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool ScanUndergo MUGA scan	Procedure or surgery	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
NavitoclaxAlso: A-855071.0, ABT-263, BcI-2 Family Protein Inhibitor ABT-263Given PO	Biological	Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 8 (Remission induction with venetoclax and navitoclax)
NelarabineAlso: 2-Amino-6-methoxypurine arabinoside, 506U78, Arranon, Compound 506U78Given IV	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
PegaspargaseAlso: L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-AsparaginaseGiven IV	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
Positron Emission TomographyAlso: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)Undergo PET scan	Procedure or surgery	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
ThioguanineAlso: 2-Amino 6MP, 2-Amino-1,7-dihydro-6H-purine-6-thione, 2-Amino-6-mercaptopurine, 2-Amino-6-purinethiolGiven PO	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
VenetoclaxAlso: ABT-0199, ABT-199, ABT199, GDC-0199Given PO	Drug	Arm 2 (AALL0434 regimen with venetoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 8 (Remission induction with venetoclax and navitoclax)
VincristineAlso: LCR, Leurocristine, VCR, VincrystineGiven IV	Drug	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 7 (AALL0434 regimen), Arm 8 (Remission induction with venetoclax and navitoclax)
X-Ray ImagingAlso: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographsUndergo X-ray	Procedure or surgery	Arm 1 (AALL0434 regimen), Arm 2 (AALL0434 regimen with venetoclax), Arm 3 (AALL0434 regimen with navitoclax), Arm 4 (AALL0434 regimen with venetoclax and navitoclax), Arm 5 (AALL0434 [no nelarabine]), Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax), Arm 8 (Remission induction with venetoclax and navitoclax)

Primary outcome

Incidence of adverse events (Cohorts 1, 2 and 3)
Time frame: Up to 10 years
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events will be used to determine severity of toxicity.
Undetectable minimal residual disease (MRD) (Cohort 1)
Time frame: At day 29 following induction
There will be three primary analyses, each comparing an experimental arm with the shared control arm using Fisher's exact test with a one-sided alpha of 10%. All eligible randomized participants will be used in the efficacy comparison.
Percent of participants with detectable disease in the bone marrow (Cohort 2)
Time frame: At diagnosis and at days 29 and 57
Binomial estimates will be reported along with exact 95% confidence intervals.
Undetectable MRD (Cohorts 1 and 3)
Time frame: At days 29 and 78
Binomial estimates will be reported along with exact 95% confidence intervals.

8 secondary outcomes

Rate of complete remission (CR)
Time frame: End of consolidation therapy
Rate of complete remission with incomplete count recovery (CRi) with and without MRD
Time frame: End of consolidation therapy
Event free survival
Time frame: From the date of initial registration on study until the first of the following events: death from any cause, relapse from MRD-negative remission, or completion of protocol therapy without documentation of MRD-negative remission, up to 10 years
Relapse free survival
Time frame: From the date the participant first achieves CR or CRi until relapse from CR/CRi or death from any cause, up to 10 years
Overall survival
Time frame: From the day of registration to death from any cause, up to 10 years
Incidence of adverse events
Time frame: Up to 10 years
Serum asparaginase activity levels
Time frame: At day 8 and day 15 of induction, day 19 and 26 of consolidation and day 6 and 13 of interim maintenance
Incidence of adverse events associated with reduced doses of Peg-asparaginase
Time frame: Up to 10 years

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2024.
Individual participant dataSharing planned: Yes. "NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kristen M O'Dwyer principal investigator

SWOG Cancer Research Network

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (Cohorts 1, 2 and 3) (time frame: Up to 10 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06210750.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2024.