Venetoclax and Chemotherapy as Frontline Therapy in Older Patients and Patients With Relapsed/Refractory ALL

Inclusion Criteria: * Patients with previously untreated acute lymphoblastic leukemia (B-cell or T-cell) * Bone marrow involvement with ≥20% lymphoblasts * Age ≥ 60 Years OR * Patients with relapsed or refractory acute lymphoblastic leukemia (B-cell or T-cell) defined as receiving one or more cytotoxic containing regimens * Bone marrow involvement with ≥5% lymphoblasts * Age ≥ 18 Years * Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Refer to Appendix D) * Adequate organ function * Serum total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN, unless clearly due to disease involvement * Creatinine clearance \>50 mL/min (calculated according to institutional standards or using Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula) * Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use an effective contraception method during the study and for 30 days following the last dose of study drug. Women of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug * Patients or their legally authorized representative must provide written informed consent Exclusion Criteria: * Ph-positive ALL, Burkitt's leukemia/lymphoma, or lymphoblastic lymphoma * Patient is pregnant or breastfeeding * Patients with uncontrolled infection * Hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV) * Major surgery or radiation therapy within 4 weeks prior to the first study dose * Systemic chemotherapy/radiotherapy/investigational therapy within 14 days (with the exception of hydroxyurea and/or dexamethasone, or one dose of cytarabine) prior to starting therapy * Symptomatic or untreated leptomeningeal disease or spinal cord compression * Patients with active heart disease (New York Heart Association (NYHA) class 3-4 as assessed by history and physical examination, unstable angina/stroke/myocardial infarction within the last 6 months) * Patients with a cardiac ejection fraction (as measured by either Multi Gated Acquisition (MUGA) or echocardiogram (EKG)) \<40% * History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses) * Concurrent use of warfarin * Received Cytochrome P450 3A (CYP3A) inhibitors (such as fluconazole, ketoconazole, voriconazole, and clarithromycin) within 3 days of starting venetoclax; received strong CYP3A inducers (such as rifampin, rifabutin, phenytoin, carbamazepine, and St. John's Wort) within 3 days of starting venetoclax * Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax * Prior treatment with venetoclax * Malabsorption syndrome or other conditions that preclude enteral route of administration * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study