A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Participants With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy

Inclusion Criteria:

• Participant must have confirmation of Acute Myeloid Leukemia (AML) by World HealthOrganization (WHO) criteria, previously untreated and be ineligible for treatmentwith a standard cytarabine and anthracycline induction regimen due age orcomorbidities.

• Participant must be >= 18 years of age.

• Participant must have a projected life expectancy of at least 12 weeks.

• Participant must be considered ineligible for induction therapy defined by thefollowing: a. >= 75 years of age; or b. >= 18 to 74 years of age with at least one of thefollowing comorbidities: i. Eastern Cooperative Oncology Group (ECOG) PerformanceStatus of 2 or 3; ii. Cardiac history of Congestive Heart Failure (CHF) requiringtreatment or Ejection Fraction <= 50% or chronic stable angina; iii. Diffusingcapacity of the Lung for Carbon Monoxide (DLCO) <= 65% or Forced Expiratory Volumein 1 second (FEV1) <= 65%; iv. Creatinine clearance >= 30 mL/min to < 45 ml/min; v.Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × Upper Limit ofNormal (ULN); vi. Any other comorbidity that the physician judges to be incompatiblewith intensive chemotherapy must be reviewed and approved by the AbbVie TherapeuticMedical Director during screening and before study enrollment.

• Participant must have an ECOG Performance status:

1. 0 to 2 for Participants >= 75 years of age or

2. 0 to 3 for Participants >= 18 to 74 years of age.

• Participant must have adequate renal function as demonstrated by a creatinine >= 30mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urinecollection.

• Participant must have adequate liver function as demonstrated by:

1. aspartate aminotransferase (AST) <= 3.0 x ULN*

2. alanine aminotransferase (ALT) <= 3.0 x ULN*

3. bilirubin <= 1.5 x ULN* * Unless considered to be due to leukemic organinvolvement i. Participants who are < 75 years of age may have a bilirubin of <= 3.0 x ULN

• Female participants must be either postmenopausal defined as:

1. Age > 55 years with no menses for 12 or more months without an alternativemedical cause.

2. Age ≤ 55 years with no menses for 12 or more months without an alternativemedical cause AND an follicle stimulating hormone (FSH) level >40 internationalunits per liter (IU/L); or

3. Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomyor hysterectomy); or

4. Women of Childbearing Potential (WOCBP) practicing at least one protocolspecified method of birth control, starting at Study Day 1 through at least 90days after the last dose of study drug.

• Male participants who are sexually active, must agree, from Study Day 1 through atleast 90 days after the last dose of study drug, to practice the protocol specifiedcontraception. Male subjects must agree to refrain from sperm donation from initialstudy drug administration through at least 90 days after the last dose of studydrug.

• Female participants of childbearing potential must have negative results forpregnancy test performed:

1. At Screening with a serum sample obtained within 14 days prior to the firststudy drug administration, and

2. Prior to dosing with urine sample obtained on Cycle 1 Day 1, if it has been > 7days since obtaining the serum pregnancy test results.

• Participant must voluntarily sign and date an informed consent, approved by anIndependent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to theinitiation of any screening or study-specific procedures.

Exclusion Criteria:

• Participant has received treatment with the following:

1. A hypomethylating agent, venetoclax and/or chemo therapeutic agent forMyelodysplastic syndrome (MDS).

2. Chimeric Antigen Receptor (CAR)-T cell therapy.

3. Experimental therapies for MDS or Acute Myeloid Leukemia (AML).

4. Current participation in another research or observational study.

• Participant has history of myeloproliferative neoplasm (MPN) includingmyelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloidleukemia (CML) with or without BCR-ABL1 translocation and AML with BCR-ABL1translocation.

• Participant has the following: a. Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) asper the National Comprehensive Cancer Network (NCCN) Guidelines Version 2, 2016 forAcute Myeloid Leukemia.

• Participant has acute promyelocytic leukemia

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

• Participant has known human immunodeficiency virus (HIV) infection (due to potentialdrug-drug interactions between antiretroviral medications and venetoclax) HIVtesting will be performed at Screening, only if required per local guidelines orinstitutional standards.

• Participant is known to be positive for hepatitis B or C infection [HCV Abindicative of a previous or current infection; and/or positive HBs Ag or detectedsensitivity on hepatitis B virus (HBV) deoxyribonucleic acid (DNA) polymerase chainreaction (PCR) test for HBc Ab and/or HBs Ab positivity] with the exception of thosewith an undetectable viral load within 3 months screening. Hepatitis B or C testingis not required.

• Participant has received strong and/or moderate CYP3A inducers within 7 days priorto the initiation of study treatment; additional details as described in theprotocol.

• Participant has consumed grapefruit, grapefruit products, Seville oranges (includingmarmalade containing Seville oranges) or Starfruit within 3 days prior to theinitiation of study treatment.

• Participant has a cardiovascular disability status of New York Heart AssociationClass > 2. Class 2 is defined as cardiac disease in which patients are comfortableat rest but ordinary physical activity results in fatigue, palpitations, dyspnea, oranginal pain.

• Participant has chronic respiratory disease that requires continuous oxygen, orsignificant history of renal, neurologic, psychiatric, endocrinologic, metabolic,immunologic, hepatic, cardiovascular disease, any other medical condition or knownhypersensitivity to any of the study medications including excipients of azacitidinethat in the opinion of the investigator would adversely affect his/her participatingin this study.

• Participant has a malabsorption syndrome or other condition that precludes enteralroute of administration.

• Participant exhibits evidence of other clinically significant uncontrolled systemicinfection requiring therapy (viral, bacterial or fungal).

• Participant has a history of other malignancies within 2 years prior to study entry,with the exception of:

1. Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situof breast;

2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of theskin;

3. Previous malignancy confined and surgically resected (or treated with othermodalities) with curative intent; requires discussion with TA MD.

• Participant has a white blood cell count > 25 × 10^9/L. (Hydroxyurea orleukapheresis are permitted to meet this criterion.)