Venetoclax in Combination With Intensive Induction and Consolidation Chemotherapy in Treatment Naïve AML

Inclusion Criteria: * Patients with AML who are newly diagnosed according to the WHO 2016 Classification and previously untreated with the exception of hydroxyurea. ATRA pretreatment for suspected APL for less than 5 days is allowed. Eligible patients with AML arising from an antecedent hematologic disease (AHD) including MDS, may have been treated for their prior hematologic disease (except for allogenic transplant). * AML patients include de-novo AML, AML evolving from MDS or other AHD and AML after previous cytotoxic therapy or radiation (secondary AML). * For a diagnosis of AML, a bone marrow or peripheral blast count of 20% or more is required. * In AML with monocytic or myelomonocytic differentiation, monoblasts and promonocytes, but not abnormal mature monocytes, are counted as blast equivalents. * Patients must be ≥18 and ≤60 years old. * Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2. (See protocol Appendix D.) * LVEF ≥ 45% by MUGA or ECHO at screening. * Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 50 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula. * Adequate liver function as demonstrated by: * aspartate aminotransferase (AST) ≤ 2.5 × ULN\* * alanine aminotransferase (ALT) ≤ 2.5× ULN\* * total bilirubin ≤ 1.5 × ULN\* * Unless considered due to leukemic organ involvement. * Subjects with Gilbert's Syndrome may have a total bilirubin \> 1.5 × ULN per discussion with the overall study PI * Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug. * Females of childbearing potential (i.e., not postmenopausal for at least 1 year or not surgically sterile) must have negative results by a serum pregnancy test performed within 7 days of day 1. * Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures. Exclusion Criteria: * Subject has acute promyelocytic leukemia, inversion16, t(8;21) or FLT3 mutant AML as described below. Contact PI with questions. * Inversion 16 and t(8;21): CBF chromosomal abnormalities may be assessed by molecular (PCR), metaphase cytogenetics, or FISH * FLT3: ITD or a point mutation in the TKD loop of variant allele fractions ≥5% by PCR, capillary electrophoresis, or NGS panel capable of defining FLT3 allelic burden * Subject has known active CNS involvement with AML. * Subject has tested positive for HIV (due to potential drug-drug interactions between antiretroviral medications and venetoclax, as well as anticipated venetoclax mechanism-based lymphopenia that may potentially increase the risk of opportunistic infections). Note: HIV testing is not required. * Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV \[i.e., HBs Ag-, and anti-HBs+\] are allowed. * Subject has received the following within 7 days prior to the initiation of study treatment: * Strong or moderate CYP3A inducers (see Appendix C) * Strong and moderate CYP3A inhibitors (see Appendix C) * Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment. * Subject has a cardiovascular disability status of New York Heart Association Class ≥ 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain. * Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study. * Subject has chronic respiratory disease that requires continuous oxygen use. * Subject has a malabsorption syndrome or other condition that precludes enteral route of administration. * Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: uncontrolled systemic infection. * Subject has a history of other malignancies prior to study entry, with the exception of: * Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; * Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; * Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. * Prior malignancies treated with (surgery+/- chemotherapy+/- radiation) that have remained disease free for at least two years after completion of therapy * Subject has a white blood cell count \> 25 × 109/L. Note: Hydroxyurea is permitted to meet this criterion. * Subject treated with any form of chemotherapy, immunotherapy, or investigative agent within 1 month of enrollment.