Venetoclax or Placebo in Combination With Reduced-Intensity Conditioning Hematopoietic Cell (Bone Marrow/Blood Stem Cell) Transplant and as Maintenance Therapy After Transplant in Patients With Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)

Inclusion Criteria:

* Patients must be registered to the Master Screening and Reassessment Protocol (MSRP) and assigned to this protocol by the MATCHBox Treatment Verification Team
* STEP 1: History of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria in first complete remission with morphologic complete remission (CR) or CR with incomplete hematologic recovery (CRi) defined as less than 5% bone marrow blasts by morphology with no circulating leukemic myeloblasts and no known extramedullary disease
* STEP 1: MRD status by MDNet must have been performed
* STEP 1 COHORT 1: Human leukocyte antigen (HLA)-matched donor defined as one of the following:

  * Sibling donor must be a 6/6 match at HLA-A and -B (intermediate or higher resolution) and -DRB1 (at high resolution using deoxyribonucleic acid \[DNA\]-based typing)
  * Related donor other than sibling must be an 8/8 match for HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing
  * Unrelated donor must be an 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing
  * Age 40-75 years
* STEP 1 COHORT 1: Not recommended for a myeloablative regimen by treating investigator
* STEP 1 COHORT 2: Haploidentical or HLA-mismatched unrelated donor defined as one of the following:

  * Haploidentical donors: Related donor must be a haploidentical 3/6, 4/6, or 5/6 match at HLA-A and -B (intermediate or higher resolution) and -DRB1 (at high resolution using DNA-based typing)
  * HLA-mismatched unrelated donors: Unrelated donor must be a 6/8 or 7/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing, ideally age \< 35
  * Age 18-75 years
* STEP 1 COHORT 2: Not recommended for a myeloablative regimen by treating investigator
* STEP 1: Prior venetoclax therapy is allowed unless there is evidence of progression or no response (failure to achieve remission) to venetoclax-based regimen \< 2 months prior to registration
* STEP 1: No prior allogeneic or autologous hematopoietic cell transplantation
* STEP 1: Anti-leukemic therapy must be completed more than 14 days prior to registration with the exception of venetoclax
* STEP 1: Karnofsky performance status ≥ 60
* STEP 1: Total bilirubin \< 2 x upper limit of normal (ULN)
* STEP 1: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) \< 3 x upper limit of normal (ULN)
* STEP 1: Alkaline phosphatase ≤ 2.5 x upper limit of normal (ULN)
* STEP 1: Pulmonary function diffusion capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) ≥ 40% and forced expiratory volume (FEV1) ≥ 50%
* STEP 1: Calculated (Calc.) creatinine clearance ≥ 40 mL/min/based on the Cockcroft-Gault formula
* STEP 1: Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 7 days prior to registration is required
* STEP 1: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* STEP 1: Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
* STEP 1: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* STEP 1: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* STEP 1: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association (NYHA) Functional Classification. To be eligible for this trial, patients should have ejection fraction ≥ 40% and NYHA functional status class II or better
* STEP 1: No history of liver cirrhosis
* STEP 1: No history of sinusoidal occlusion syndrome of the liver
* STEP 1: No known intolerance or allergy to any protocol-defined agents
* STEP 1: No known medical condition causing an inability to swallow oral formulations of agents
* STEP 2: Patient has completed the conditioning and transplantation regimens
* STEP 2: Patient has no evidence of AML morphologic relapse
* STEP 2: Patient does not have flow measurable/minimal residual disease by myeloMATCH central labs (MDNet) testing defined as ≥ 0.1% on day 100+ (between day 80+ and 110+) marrow
* STEP 2: Absolute neutrophil count \> 1,000/mcL (confirmed by a lab draw performed on two separate occasions \[\> 2 days apart\])
* STEP 2: Platelet count \> 50,000/mcL
* STEP 2: AST (SGOT)/ALT (SGPT) \< 3 x upper limit of normal (ULN)
* STEP 2: Total bilirubin \< 2 mg/dL x upper limit of normal (ULN)
* STEP 2: Calc. creatinine clearance ≥ 40 mL/min/based on the Cockcroft-Gault formula
* STEP 2: Patient does not have active/current grade 3-4 acute GVHD
* STEP 2: Patient does not have evidence of grade 3 or higher sinusoidal occlusion syndrome/veno-occlusive disease of the liver as defined by European Society for Blood and Marrow Transplantation (EBMT) criteria