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

Eligibility Criteria

• * Documented informed consent of the participant and/or legally authorized representative
• * Age between 18 and 54 years
• * Eastern Cooperative Oncology Group (ECOG) =\< 2
• * Histologically confirmed B-cell ALL according to World Health Organization criteria
• * Note: Lymphoblastic leukemia is included as long as there is bone marrow involvement
• * Newly diagnosed disease with \>= 5% blasts in the marrow
• * White blood cell count less than 25 x 10\^9/L prior to initiation of venetoclax. Cytoreduction with hydroxyurea or steroid or a single dose of intrathecal chemotherapy prior to treatment may be required (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• * Total bilirubin =\< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease or underlying leukemia, =\< 3 X ULN) (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• * Aspartate aminotransferase (AST) =\< 2.5 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• * Unless it is related to underlying leukemia
• * Alanine aminotransferase (ALT) =\< 2.5 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• * Unless it is related to underlying leukemia
• * Creatinine clearance of \>= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• * Left ventricular ejection fraction (LVEF) \>= 50%
• * Note: Echocardiogram to be performed within 42 days prior to day 1 of protocol therapy
• * Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. (performed within 14 days prior to Day 1 of protocol therapy unless otherwise stated)
• * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• * Agreement by females and males of childbearing potential\* to use an effective method of birth control (non-hormonal) or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
• * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only
• * Leukemia-based therapy with chemotherapy with the exception of:
• * Cytoreduction with steroid or hydroxyurea or a single dose of intrathecal chemotherapy is allowed before initiating the study
• * Strong or moderate CYP3A4 inducers within 14 days prior to day 1 of protocol therapy
• * Subjects who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the first dose of study drug
• * Live vaccines
• * Philadelphia chromosome positive (Ph+; t(9;22)), MLL-rearrangement, t(12;21), and t(1;19)
• * T cell ALL
• * Class III/IV cardiovascular disability according to the New York Heart Association Classification. Subjects with controlled, asymptomatic atrial fibrillation can enroll
• * Parenchymal central nervous system (CNS) involvement requiring cranial radiation
• * Participants with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of enrollment
• * History of acute cardiovascular ischemic event, i.e., myocardial infarction or unstable angina within 6 months of enrollment
• * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• * Clinically significant uncontrolled illness
• * Uncontrolled active infection
• * Other active malignancy
• * Females only: Pregnant or breastfeeding
• * Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)