Venetoclax and a Pediatric-Inspired Regimen for the Treatment of Newly Diagnosed B Cell Acute Lymphoblastic Leukemia

PRIMARY OBJECTIVES: I. To assess the safety and tolerability of combining venetoclax with the C10403 regimen backbone during induction and consolidation in newly diagnosed adults with B cell acute lymphoblastic leukemia (ALL). II. To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose/schedule (RP2D) of venetoclax in combination with the C10403 regimen. SECONDARY OBJECTIVES: I. To estimate complete response (CR) after induction. II. To estimate composite CR (CR or CR with incomplete hematologic recovery \[CRi\] or CR with partial hematologic recovery \[CRh\]) after induction. III. To estimate minimal residual disease (MRD) negativity after induction. IV. To estimate MRD negativity after consolidation. V. To estimate CR after induction for Philadelphia (Ph)-like ALL. VI. To estimate CR/CRi/CRh after induction for Ph-like ALL. VII. To estimate MRD negativity after induction for Ph-like ALL. VIII. To estimate MRD negativity after consolidation for Ph-like ALL. IX. To estimate leukemia-free survival (LFS) and overall survival (OS). OUTLINE: INDUCTION: Patients receive venetoclax orally (PO) on days 1-14. Patients also receive cytarabine intrathecally (IT) on day 1, prednisone PO twice daily (BID) on days 1-28, vincristine intravenously (IV) on days 1, 8, 15 and 22, daunorubicin IV on days 1, 8, 15 and 22, pegaspargase intramuscularly (IM) or IV on day 4, and methotrexate IT on days 8 and 29 (and also on days 15 and 22 for central nervous system \[CNS\]3 patients) in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD) or partial response (PR) after Induction proceed to Extended Induction. Patients with CR, CRi, or CRh after Induction proceed to Consolidation. EXTENDED INDUCTION: Patients receive venetoclax PO on days 1-7, prednisone PO BID on days 1-14, vincristine IV on days 1 and 8, daunorubicin IV on day 1, and pegaspargase IM or IV on day 4 in the absence of disease progression or unacceptable toxicity. Patients with CR, CRi, or CRh after Extended Induction proceed to Consolidation. CONSOLIDATION: Patients receive venetoclax PO on days 1-14, cyclophosphamide IV on days 1 and 29, cytarabine IV or subcutaneously (SC) 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, pegaspargase IM or IV on days 15 and 43, and methotrexate IT on days 1, 8, 15 and 22 (omit on days 15 and 22 for CNS3 patients) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year.