Venetoclax Plus Intensive Chemotherapy in AML and Advanced MDS

Inclusion Criteria:

* New diagnosis of AML by WHO criteria. Patients with higher risk MDS (R-IPSS\>3.5) and 10% blasts or more, or proliferative (WBC ≥ 13 x 10⁹/L) CMML-2 are also eligible at the discretion of the PI. Patients having received any prior hypomethylating agent with or without BCL2 inhibitor therapy for MDS/AML are also eligible at the discretion of the PI
* Patients ≥ 18 to ≤ 75 years.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
* Adequate renal function including creatinine clearance \> 30 mL/min based on the Cockcroft Gault equation.
* Adequate hepatic function including total bilirubin \< 1.5x ULN unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement
* Ability to understand and provide signed informed consent
* 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.

Exclusion Criteria:

* Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (FAB class M3-AML)
* Subject has known active CNS involvement with AML
* Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF \<45% by echocardiogram or multi-gated acquisition (MUGA) scan
* Patients with a history of myocardial infarction within the last 6 months or unstable / uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias
* Patients with uncontrolled infection with human immunodeficiency virus (HIV) or active Hepatitis B or C
* Patients with known dysphagia, short-gut syndrome, or other conditions that would affect the ingestion or gastrointestinal absorption of drugs administered orally.
* Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study.
* Subject has a white blood cell count \> 25 x 10⁹/L. (Note: Hydroxyurea and/or cytarabine (up to 2 g/m\^2 is permitted to meet this criterion.)
* Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception. Appropriate method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).