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.
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.
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).
Parallel
Dexamethasone
DrugGiven orally (PO) or intravenously (IV).
Vincristine
DrugGiven IV.
Daunorubicin
DrugGiven IV.
Calaspargase pegol
DrugGiven IV.
Dasatinib
DrugGiven PO
Venetoclax
DrugGiven PO (ETP, near-ETP, and MPAL only).
Bortezomib
DrugGiven IV (T-LLy only).
Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine)
DrugGiven Intrathecal (IT), Age adjusted.
Cyclophosphamide
DrugGiven IV.
Cytarabine
DrugGiven IV or IT.
Mercaptopurine
DrugGiven PO.
Nelarabine
DrugGiven IV
Methotrexate
DrugGiven IT, IV, PO or intramuscular (IM).
Thioguanine
DrugGiven PO (participants intolerant to mercaptopurine).
Minimal residual disease (MRD)-negativity rate in patients with T cell acute lymphoblastic leukemia
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
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.
Event-free survival (EFS)
Kaplan-Meier estimates for EFS will be calculated along with standard error.
Overall survival (OS)
Kaplan-Meier estimates for OS will be calculated along with standard error.
Incidence of grade 4 toxicities
Adverse events will be graded using Common Terminology Criteria for Adverse Events version 5 and compared using Fisher's or exact Chi-square test.
EFS compared to Total 17 (TOT17-NCT03117751)
Comparisons of EFS to the corresponding TOT17 will be performed by the log-rank test.
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St. Jude Children's Research Hospital
Lead sponsor
AbbVie
Collaborator
