Decitabine and Cedazuridine in Combination With Venetoclax for the Treatment of Patients Who Have Relapsed Acute Myeloid Leukemia After Donor Stem Cell Transplant

Inclusion Criteria:

* Age \>= 18 years at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF and meet all study requirements
* History of morphologically confirmed AML (per World Health Organization \[WHO\] diagnostic criteria) with evidence of disease recurrence (\>= 5% blasts consistent with prior disease) that occurs after allogeneic hematopoietic cell transplantation (HCT). Patients transplanted for another indication (e.g., myelodysplastic syndrome/chronic myelomonocytic leukemia \[MDS/CMML\]) who relapse with AML are eligible to enroll
* White blood cells (WBC) must be less than 25,000/ul for at least three days prior to cycle 1, day 1 (C1D1) (hydroxyurea allowed)
* A bone marrow biopsy must be performed and tissue collected for entrance to the trial
* Eastern Cooperative Oncology Group Performance Status of 0 - 2
* Alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT) and/or aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) less than or equal to 3x upper limit of normal (ULN)
* Total bilirubin \< 1.5 x ULN

  \* Patients with Gilbert's syndrome (hereditary indirect hyperbilirubinemia) must have a total bilirubin of \< 3 x ULN
* Calculated creatinine clearance \>= 30 ml/min (per the Cockroft-Gault formula)
* Willingness to abide by all study requirements, including contraception, maintenance of a pill diary, and acceptance of recommended supportive care medications

Exclusion Criteria:

* Prior relapse or progression while receiving venetoclax or other commercially available or investigational BCL-2 inhibitor
* Anticancer therapy, including investigational agents =\< 2 weeks or =\< 5 half-lives of the drug, whichever is shorter, prior to C1D1. (Use of hydroxyurea is permitted)
* Inadequate recovery from toxicity attributed to prior anti-cancer therapy to =\< Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version \[v\]5.0), excluding alopecia or fatigue
* History of allogeneic HCT, or other cellular therapy product, within 3 months of signing consent
* Clinically active acute or chronic graft versus host disease (GVHD). Patients must be off calcineurin inhibitors for at least 4 weeks to be eligible
* Radiation therapy or major surgery within 3 weeks of signing consent
* Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible. Prophylaxis is acceptable
* Inability to tolerate oral medication, presence of poorly controlled gastrointestinal disease, or dysfunction that could affect study drug absorption
* Active documented central nervous system leukemia
* Concurrent treatment with a non-permitted concomitant medication
* Other malignancy IF currently being treated or likely to be treated in next 6 months except for basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
* Pregnancy or breastfeeding females
* Known chronic alcohol or drug abuse
* Clinically significant cardiovascular disease with major event or cardiac intervention within the past 6 months (e.g. percutaneous intervention, coronary artery bypass graft, documented cardiac heart failure) as determined by the investigator
* Any other condition deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents