Testing the Use of Combination Therapy in Patients With Persistent Low Level Acute Myeloid Leukemia Following Initial Treatment, The ERASE Study (A MyeloMATCH Treatment Trial)

Inclusion Criteria

• •Patient must be \>= 18 and =\< 59 years of age
• •Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• •Patient must have morphologically documented AML or secondary AML (from prior conditions such as myelodysplastic syndrome \[MDS\], myeloproliferative neoplasm \[MPN\]) or therapy related AML (t-AML), as defined by World Health Organization (WHO) criteria
• •Patient must have completed induction chemotherapy in a myeloMATCH young adult tier-1 protocol. Patient may have received prior hypomethylating agents (HMAs). Patient may have received prior azacitidine + venetoclax
• •Patient must have been assigned to this protocol by myeloMATCH master screening and reassessment protocol (MSRP)/MATCHBOX. Patients thereby assigned will have attained complete remission (CR) or CR with partial hematologic recovery (CRh) (defined as CR with \[absolute neutrophil count (ANC)\] \>= 500/mcL and/or platelets \> 50/mcL) with detectable MRD at time of assignment. MRD is defined as \> 0.1% flow cytometry on bone marrow (BM) biopsy as assessed by MDNet. The definition of CR or CRh may be made +/- 2 weeks from BM biopsy
• •Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
• •Patient must have recovered (i.e.: resolved to \< grade 2) from adverse events related to prior anti-cancer therapy at the time of randomization with the exception of alopecia
• •Absolute neutrophil count (ANC) \>= 500/mcL (obtained =\< 7 days prior to protocol randomization)
• •Platelets \>= 50,000/mcL (obtained =\< 7 days prior to protocol randomization)
• •Total bilirubin =\< 2 x institutional upper limit of normal (ULN) (obtained =\< 7 days prior to protocol randomization)
• •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN (obtained =\< 7 days prior to protocol randomization)
• •Creatinine =\< 1.5 x institutional ULN OR \>= 50 mL/min.1.73 m\^2 (obtained =\< 7 days prior to protocol randomization)
• •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
• •For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• •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
• •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 Functional Classification. To be eligible for this trial, patients should be class 2B or better
• •Patients must be able to swallow oral tablets and be free of gastrointestinal (GI) absorption issues