Enasidenib as Maintenance Therapy in Treating Patients With Acute Myeloid Leukemia With IDH2 Mutation After Donor Stem Cell Transplant

Inclusion Criteria:

Documented informed consent of the participant and/or legally authorized representative

Agreement to allow the use of archival tissue from diagnostic tumor biopsies

If unavailable, exceptions may be granted with study principal investigator (PI) approval
Eastern Cooperative Oncology Group (ECOG) =< 2 or Karnofsky performance status (KPS) >= 70
Recipients of allogeneic HCT - all stem cell sources including sibling, unrelated, mismatched related/unrelated, cord and haploidentical transplant patients will be included
Conditioning regimen: Investigator's choice based on center guidelines
GvHD prophylaxis: sirolimus + tacrolimus or tacrolimus + methotrexate or investigator choice
Patients must have acute myeloid leukemia (AML) with IDH2 mutation at diagnosis. Day 30 marrow post HCT should show evidence of morphologic remission with < 5% bone marrow blasts. Patients with MRD either by flow cytometry or IDH2 mutation testing will be allowed
Patients with previous therapy with IDH2 inhibitors will be included
Absolute neutrophil count (ANC) > 1000 (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
Hemoglobin >= 9.5 gm% (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
Platelets > 50,000/mm^3 (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

Platelets >= 20,000/mm^3 (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

NOTE: Patients with lower counts can enroll if infection cytomegalovirus (CMV)/human herpesvirus 6 (HHV6) etc. is being treated actively
Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
Total bilirubin < 2.0 mg/dl-exception permitted in patients with Gilbert's Syndrome (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x ULN, patients with abnormal liver function tests (LFTs) in the context of active GVHD will not be included (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
Creatinine clearance of >= 40/min/1.73 m^2 for participants with creatinine levels above institutional normal per 24 hour urine test or the Cockcroft-Gault formula (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

Corrected QT (QTc) =< 480 ms

Note: To be performed within 28 days prior to day 1 of protocol therapy

Seronegative for human immunodeficiency virus (HIV) antigen/antibody (Ag/Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR])

If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed

Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy

Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
Active diarrhea considered clinically significant and may impair oral drug administration
Clinically significant uncontrolled illness

Active infection requiring antibiotics

Active infection. Patients with treated viral, bacterial or fungal infections that are controlled on therapy will be allowed to participate
Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
Diagnosis of Gilbert's disease
Other active malignancy. Participants with history of prior malignancy treated with curative intent who achieved complete response (CR) more than 2 years before study entry are eligible. This exclusion rule does not apply to non-melanoma skin tumors and in-situ cervical cancer
Females only: Pregnant or breastfeeding
Active grade II-IV acute GVHD and/or requiring systemic steroids with prednisone dose equivalent of >= 0.25 mg/kg at end of 4 weeks
Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants, who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)