Pevonedistat and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission AML

Inclusion Criteria: 1. Age ≥ 18 years (or age of majority at participating site, whichever is greater) and ≤ 70 years. 2. Non-remission AML at the time of transplant proven via bone marrow aspiration and/or biopsy. o"Not in remission" is defined as "greater than 5.0% bone marrow blasts by aspirate morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration. * For primary induction failure patients: Patients must have failed at least 2 induction regimens. * For patients with relapsed disease: Patients who relapse more than 6 months after preceding remission must fail at least one reinduction regimen to be eligible. For patients in whom the preceding remission is equal to or shorter than 6 months duration, no re-induction regimen is required to qualify for this protocol. * If the pre-transplant bone marrow aspirate and biopsy are hypo plastic (less than 10% cellularity), and blast percentages cannot be determined, the patient is eligible if the preceding bone marrow met the above criteria. * Patients with peripheral circulating blasts or patients with extramedullary leukemia are eligible if bone marrow aspirate and biopsy meets the above criteria. 3. Karnofsky Performance Scale (KPS) above or equal to 70% 4. Clinical laboratory values within the following parameters (repeat if more than 3 days before the first dose): 1. Creatinine clearance ≥ 50 mL/min 2. Hemoglobin \> 8 g/dL. Patients may be transfused to achieve this value. 3. White blood cell (WBC) count \< 50,000/µL before administration of Pevonedistat on Cycle 1 Day 1. Note: Hydroxyurea may be used to control the level of circulating leukemic blast cell counts to not lower than 10,000/µL during the study. 4. LFTs (ALT, AST) equal or less than 2.5 times upper limit of normal value. 5. Bilirubin ≤ x 1.5 ULN limit 5. Female patients who: * Are postmenopausal (see Appendix for definition) for at least 1 year before the screening visit, OR * Are surgically sterile, OR If they are of childbearing potential: * Agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception (see Appendix), at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.) Male patients, even if surgically sterilized (i.e., status post vasectomy), who: * Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.) 6. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. Exclusion Criteria: 1. Treatment with any investigational products within 21 days of study registration. 2. Known hypersensitivity to Azacitidine. 3. Active uncontrolled infections or severe infectious disease, such as severe pneumonia, meningitis, or septicemia. 4. Known central nervous system (CNS) involvement. 5. Known human immunodeficiency virus (HIV) positivity. 6. Known hepatitis B surface antigen-positive, or known active hepatitis C infection. * Note: Patients who have isolated positive hepatitis B core antibody (ie, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load. 7. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures 8. Major surgery within 14 days before the first dose of any study drug or a scheduled surgery during study period. 9. Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non- melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection. 10. Life-threatening illness unrelated to cancer. 11. Patients with uncontrolled coagulopathy or bleeding disorder. 12. Known hepatic cirrhosis or severe pre-existing hepatic impairment 13. Known cardiopulmonary disease defined as: * Unstable angina; * Congestive heart failure (New York Heart Association \[NYHA\] Class III or IV; see appendix); * Myocardial infarction (MI) within 6 months prior to first dose (patients who had ischemic heart disease such as a (ACS), MI, and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll); * Cardiomyopathy; * Clinically significant arrhythmia: 1. History of polymorphic ventricular fibrillation or torsade de pointes, 2. Permanent atrial fibrillation \[a fib\], defined as continuous a fib for ≥ 6 months, 3. Persistent a fib, defined as sustained a fib lasting \> 7 days and/or requiring cardioversion in the 4 weeks before screening, 4. Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g. pacemaker), or ablation and 5. Patients with paroxysmal a fib or \< Gr 3 a fib for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen. * Implantable cardioverter defibrillator; * Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing); * Pulmonary hypertension 14. Uncontrolled high blood pressure (i.e., systolic blood pressure \> 180 mm Hg, diastolic blood pressure \> 95 mm Hg). 15. Prolonged rate corrected QT (QTc) interval ≥ 500 msec, calculated according to institutional guidelines. 16. Left ventricular ejection fraction (LVEF) \< 50% as assessed by echocardiogram or radionuclide angiography. 17. Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis. 18. Systemic antineoplastic therapy or radiotherapy for other malignant conditions within 14 days before the first dose of any study drug, except for hydroxyurea. 19. Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug. 20. Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s). 21. Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s). 22. Patients who need to use clinically significant CYP3A enzyme inducers (listed on Appendix A)