A Study of Venetoclax in Combination With Chemotherapy to Treat Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

Inclusion Criteria:

* Adult patients with newly diagnosed Philadelphia chromosome (Ph) negative ALL.
* Patients with T- or B-cell lymphoblastic lymphoma with no bone marrow involvement will also be eligible for the study.
* Age 18-60
* ECOG performance status of 0-2
* Adequate renal function as demonstrated by a calculated creatinine clearance of ≥ 60 ml/min.
* Adequate hepatic function as demonstrated by a total bilirubin ≤ 2.0 mg/dl (unless attributable to Gilbert's disease) and an alkaline phosphatase, AST, and ALT ≤ 4 times the upper limit of normal (unless clinically considered to be related to liver involvement with leukemia)
* Patients with central nervous system (CNS) involvement by ALL are eligible and may receive concomitant treatment with radiation therapy and/or intrathecal chemotherapy in accordance with standard medical practice. For patients with CNS disease, dexamethasone may be temporarily administered instead of prednisone to reduce CNS pressure, at the discretion of the treating physician and after discussion with the MSK PI. Once dexamethasone is no longer needed, prednisone should be given as per protocol for 28 days.
* Negative serum pregnancy test in women of childbearing potential

Exclusion Criteria:

* CML in lymphoid blast crisis, mature B-cell (i.e. Burkitt's) lymphoma or mixed phenotype acute leukemia (MPAL)
* Prior treatments for ALL, except any doses of corticosteroids and hydroxyurea or one dose of vincristine
* Patients who received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment
* Unstable angina and/or MI or stroke within 6 months prior to screening, and/or impaired cardiac function with EF \<40% or NYHA class III/IV
* Pregnant or lactating women. Women and men of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished.
* Patients with HIV or active hepatitis B or hepatitis C infection are ineligible.
* Patients with concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of the skin, in situ cervical cancer, adequately treated stage I/II cancer from which the patient is current in complete remission, or any other cancer from which the patient has been disease free for five years.