Venetoclax Combined with Intensive Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia or Intermediate and Higher Risk Myelodysplastic Syndrome

Inclusion Criteria

• New diagnosis of AML by World Health Organization (WHO) criteria. Patients with intermediate and higher risk myelodysplastic syndrome (MDS) (Revised International Prognostic Scoring System [R-IPSS] > 3.5) and 10% blasts or more are also eligible at the discretion of the principal investigator (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
• Creatinine clearance > 30 mL/min based on the Cockcroft Gault equation
• Total bilirubin < 1.5 x upper limit of normal (ULN) unless increase is due to Gilbert’s disease or leukemic involvement
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 3 x 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 (French-American-British Classification [FAB] class M3-AML)
• Subject has known active central nervous system (CNS) involvement with AML
• Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or left ventricular ejection fraction (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 10^9/L. (Note: Hydroxyurea and/or cytarabine [1 or 2 doses; up to 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, intrauterine device (IUD), and double barrier methods (for example a condom in combination with a spermicide)