A Study of Venetoclax in Combination With Low Dose Cytarabine Versus Low Dose Cytarabine Alone in Treatment Naive Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

1. Participant has received any prior treatment for AML with the exception of hydroxyurea, allowed through the first cycle of study treatment. Note: Prior treatment for myelodysplastic syndrome is allowed except for use of cytarabine.

2. Participant had an antecedent myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia (CML) with or without BCR-ABL 1 translocation and AML with BCR-ABL 1 translocation.

3. Participants that have acute promyelocytic leukemia (APL).

4. Participant has known central nervous system (CNS) involvement with AML.

5. Participant has known human immunodeficiency virus (HIV) infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax). HIV testing will be performed at Screening, if required per local guidelines or institutional standards.

6. Participant is known to be positive for hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals (non-exclusionary medications) are not excluded.

7. Participant has received strong or moderate cytochrome P450 3A4 (CYP3A) inducers 7 days prior to the initiation of study treatment.

* Chinese subjects are excluded from receiving strong and/or moderate CYP3A inhibitors 7 days prior to the initiation of study treatment through the end of intensive pharmacokinetic (PK) collection (24 hours post dose on Cycle 1 Day 10).

8. Participant 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.

9. Participant has cardiovascular disability status of New York Heart Association Class \> 2. Class 2 is defined as cardiac disease which subjects are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or angina pain. Class 3 is defined as cardiac disease which subjects are comfortable at rest but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class 4 is defined as cardiac disease which subjects have an inability to carry on any physical activity without discomfort, symptoms of heart failure at rest, and if any physical activity is undertaken then discomfort increases.

10. Participant has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition or known hypersensitivity to any of the study medications including excipients of LDAC that in the opinion of the investigator would adversely affect his/her participating in this study.

11. Participant has a malabsorption syndrome or other condition that precludes enteral route of administration.

12. Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).

13. Participant 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.

14. Participant has a white blood cell count \> 25 × 10\^9/L. (Note: hydroxyurea administration or leukapheresis is permitted to meet this criterion).

15. Previous treatment with venetoclax and/or current participation in any other research study with investigational products.

What this study is about