Study of MLN4924 Plus Azacitidine in Treatment-naive Participants With Acute Myelogenous Leukemia (AML) Who Are 60 Years or Older

Inclusion Criteria:

1. Participants with world health organization (WHO)-defined AML, 60 years of age or older, who are unlikely to benefit from standard induction therapy, defined as having at least 1 of the following:

   * Greater than or equal to 75 years of age.
   * Antecedent hematologic disease.
   * Known adverse cytogenetic risk.
   * Eastern Cooperative Oncology Group (ECOG) PS = 2.
   * Participant must not have received definitive treatment for AML, defined as any prior chemotherapy with antileukemic activity.
2. ECOG PS 0 to 2.
3. Expected survival longer than 3 months from enrollment in the study.
4. Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence.
5. Male participants who agree to practice effective barrier contraception or agree to practice true abstinence.
6. Voluntary written consent must be given before performance of any study-related procedure.
7. Suitable venous access for the study-required blood sampling.
8. Clinical laboratory values as specified below within 3 days before the first dose of any study drug:

   •Total bilirubin must be less than or equal to (\<=) the upper limit of the normal range (ULN).
   * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be\<=2.5\*ULN.
   * Serum creatinine \<=1.5\*ULN.
   * Albumin greater than or equal to (\>=) 27 grams per liter (g/L).
   * Hemoglobin \>9 grams per deciliter (g/dL). Note: It was permissible to transfuse participants with red blood cells to achieve this criterion.
   * White blood cell (WBC) count less than (\<) 50,000 per microliter (/mcL) before administration of pevonedistat on Days 1, 3, and 5 of Cycle 1.

   Note: Hydroxyurea could be used to control the level of circulating leukemic blast cell counts to no lower than 10,000/mcL while on pevonedistat.
9. Able to undergo bone marrow aspiration and biopsy at screening.

Exclusion Criteria:

1. Previous treatment with azacitidine or decitabine.
2. Known favorable cytogenetic risk.
3. Any serious medical or psychiatric illness.
4. Treatment with any investigational products.
5. Known hypersensitivity to azacitidine or mannitol.
6. Acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis.
7. Active uncontrolled infection or severe infectious disease.
8. Major surgery within 14 days before the first dose of study drug.
9. Life-threatening illness unrelated to cancer.
10. Clinically uncontrolled central nervous system (CNS) involvement.
11. WBC count greater than (\>) 50,000/ mcL.
12. Prothrombin time (PT) or activated partial thromboplastin time (aPTT) \>1.5\* ULN or a history of coagulopathy or bleeding disorder
13. Known human immunodeficiency virus (HIV) positive.
14. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
15. Known hepatic cirrhosis or severe pre-existing hepatic impairment.
16. Known cardiac/cardiopulmonary disease defined as 1 of the following:

    * Uncontrolled high blood pressure (that is, systolic blood pressure \>180 milliliter per mercury (mm Hg), diastolic blood pressure \>95 mm Hg).
    * Congestive heart failure New York Heart Association (NYHA) Class III or IV, or Class II with a recent decompensation that required hospitalization or referral to a heart failure clinic within 4 weeks before screening (see Section 15.4 of the protocol in Appendix 16.1.1).
    * Cardiomyopathy or history of ischemic heart disease
    * Participants with ischemic heart disease who had acute coronary syndrome (ACS), myocardial infarction (MI), and/or revascularization (example, coronary artery bypass graft, stent) in the past 6 months were excluded. However, participants with ischemic heart disease who had ACS, MI, and/or revascularization greater than 6 months before screening and who are without cardiac symptoms could be enrolled.
    * Arrhythmia (example, history of polymorphic ventricular fibrillation or torsade de pointes). However, participants with \<Grade 3 atrial fibrillation (a fib) for a period of at least 6 months could enroll. Grade 3 a fib is symptomatic and incompletely controlled medically, or controlled with device (example, pacemaker), or ablation. Participants with paroxysmal a fib were permitted to enroll.
    * Implantable cardioverter defibrillator.
    * Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing).
    * Pulmonary arterial hypertension. Prolonged rate corrected QT (QTc) interval \>= 500 msec, calculated according to institutional guidelines
17. Left ventricular ejection fraction
18. Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis.
19. Body mass index \>40 kilogram per square meter (kg/m\^2).
20. Treatment with CYP3A inducers within 14 days before the first dose of MLN4924.
21. Systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of study drug, except for hydroxyurea.