SJALL23T: Adding Dasatinib Or Venetoclax To Improve Responses In Children With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) Or Lymphoma (T-LLY) Or Mixed Phenotype Acute Leukemia (MPAL)
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 100
- Locations
- 5
- Primary Endpoint
- Minimal residual disease (MRD)-negativity rate in patients with T cell acute lymphoblastic leukemia
Study Overview
Brief Summary
This is a clinical trial testing whether the addition of one of two chemotherapy agents, dasatinib or venetoclax, can improve outcomes for children and young adults with newly diagnosed T-cell acute lymphoblastic leukemia and lymphoma or mixed phenotype acute leukemia.
Primary Objective
- To evaluate if the end of induction MRD-negative rate is higher in patients with T-ALL treated with dasatinib compared to similar patients treated with 4-drug induction on AALL1231.
- To evaluate if the end of induction MRD-negative rate is higher in patients with ETP or near-ETP ALL treated with venetoclax compared to similar patients treated with 4-drug induction on AALL1231.
Secondary Objectives
- To assess the event free and overall survival of patients treated with this therapy.
- To compare grade 4 toxicities, event-free survival (EFS) and overall survival (OS) of patients treated with this therapy in induction and reinduction to toxicities of similar patients treated on TOT17.
Detailed Description
Patients will be identified in the first 3 days of therapy during their treatment on INITIALL.
Treatment will consist of 3 main phases: Induction, Early Post Induction [including Consolidation, High-Dose Methotrexate, Intensification, Interim 1, Reinduction 1, Interim 2, and Reinduction 2], and Maintenance.
Induction:
- Remission Induction includes 3 days of therapy on the INITIALL classification protocol as well as the remainder of a total of 4 weeks of induction treatment on this trial. Treatment includes a total of 28 days of dexamethasone, 4 weekly doses of vincristine, 3 doses of daunorubicin, 1 dose of Calaspargase pegol, 6 doses of Intrathecal triple therapy (IT MHA), and one of 3 additional drugs. Patients with T-ALL without near-ETP or ETP phenotype (hereafter referred to simply as T-ALL) will receive 25 days of dasatinib. Patients with ETP or near-ETP ALL as well as those with MPAL will receive 14 days of venetoclax. Patients with T-LLy will receive bortezomib. Patients will have a week without chemotherapy at the end of Induction, although patients with Induction failure (MRD ≥5% disease) will proceed directly to consolidation.
Early Post Induction:
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Enrollment on INITIALL.
- •Age 1-18.99 years at the time of enrollment on INITIALL.
- •T-Acute lymphoblastic leukemia or lymphoblastic lymphoma or mixed phenotype acute leukemia/ lymphoma
- •No prior chemotherapy excluding therapy given on or allowed by INITIALL.
- •Patient has completed no more than 3 days of chemotherapy on INITIALL.
- •Direct bilirubin ≤ 1.5x the upper limit of normal for age
- •Alanine aminotransferase (ALT) ≤ 5x the upper limit of normal for age
- •Calculated glomerular filtration rate (GFR) ≥ 50 mL/min/1.73m^2 using the Bedside Schwartz equation OR creatinine below or equal to the maximum defined below:
- •Age: 1 to < 2 years - Maximum serum creatinine (mg/dL): 0.6 (Male), 0.6 (Female)
- •Age: 2 to < 6 years - Maximum serum creatinine (mg/dL): 0.8 (Male), 0.8 (Female)
- •Age: 6 to < 10 years - Maximum serum creatinine (mg/dL): 1 (Male), 1 (Female)
- •Age: 10 to < 13 years - Maximum serum creatinine (mg/dL): 1.2 (Male), 1.2 (Female)
- •Age: 13 to < 16 years - - Maximum serum creatinine (mg/dL): 1.5 (Male), 1.4 (Female)
- •Age: ≥ 16 years - Maximum serum creatinine (mg/dL): 1.7 (Male), 1.4 (Female)
Exclusion Criteria
- •Inability or unwillingness to give informed consent/ assent as applicable.
- •Patients with > Grade 2 neuropathy at the time of enrollment (participant with T-LLy only).
- •Documented malabsorption syndrome or any other condition that precludes receipt of oral medications.
- •Known HIV infection or active hepatitis B (defined as hepatitis B surface antigen-positive) or C (defined as hepatitis C antibody-positive).
- •Pregnant or lactating.
- •For patients of reproductive potential, unwillingness to use highly effective contraception for the duration of protocol therapy and for 90 days afterwards.
- •Receipt of a strong or moderate CYP3A4 inducer such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of protocol treatment.
- •Consumption of grapefruit, grapefruit products, Seville oranges, or starfruit within 3 days of the start of protocol therapy.
Arms & Interventions
Patients with T-LLy
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib
Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine) (Drug)
Patients with T-LLy
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib
Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Cyclophosphamide (Drug)
Patients with T-LLy
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib
Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Cytarabine (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine) (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine) (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Vincristine (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Dexamethasone (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Daunorubicin (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Dasatinib (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Calaspargase pegol (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Cyclophosphamide (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Cytarabine (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Mercaptopurine (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Methotrexate (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Nelarabine (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Daunorubicin (Drug)
Patients with T-ALL (except ETP or near-ETP)
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine
Intervention: Thioguanine (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Dexamethasone (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Vincristine (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Calaspargase pegol (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Venetoclax (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Cyclophosphamide (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Cytarabine (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Methotrexate (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Mercaptopurine (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Nelarabine (Drug)
Patients with T-LLy
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib
Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Dexamethasone (Drug)
Patients with ETP or near-ETP ALL or MPAL
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax
Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Thioguanine (Drug)
Patients with T-LLy
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib
Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Bortezomib (Drug)
Patients with T-LLy
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib
Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Vincristine (Drug)
Patients with T-LLy
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib
Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Daunorubicin (Drug)
Patients with T-LLy
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib
Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Calaspargase pegol (Drug)
Patients with T-LLy
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib
Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Methotrexate (Drug)
Patients with T-LLy
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib
Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Mercaptopurine (Drug)
Patients with T-LLy
All eligible patients receive intervention according to the Detailed Description section with the following:
Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA
Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib
Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine
Intervention: Thioguanine (Drug)
Outcomes
Primary Outcomes
Minimal residual disease (MRD)-negativity rate in patients with T cell acute lymphoblastic leukemia
Time Frame: Up to end of induction day 29 or death
Comparison of the probability of achieving negative MRD (\<0.01%) and M1 bone marrow status at the end of induction between this protocol and COG AALL1231 will be performed. Statistical analysis of the primary objective will be conducted according to a group sequential design with 1 interim analysis, by a slightly modified version of the procedure for binary endpoint.
MRD-negativity rate in patients with ETP or near ETP ALL
Time Frame: Up to end of induction day 29 or death
The proportion of patients with ETP or near-ETP treated with venetoclax based induction will be compared to the rate of such unsuccessful induction in patients treated on AALL1231 with a standard 4-drug induction. The probability of achieving negative MRD will be tested using a one-sided exact binomial proportion test.
Secondary Outcomes
- Event-free survival (EFS)(Up to 10 years)
- EFS compared to Total 17 (TOT17-NCT03117751)(Up to 10 years)
- OS compared to TOT17(Up to 10 years)
- Incidence of grade 4 toxicities(Up to 30 days after last dose of study treatment)
- Overall survival (OS)(Up to 10 years)