decitabine and cedazuridine in combination with venetoclax for the treatment of patients who have relapsed acute myeloid leukemia after donor stem cell transplant

Conditions: Recurrent Acute Myeloid Leukemia

Summary: this phase ii trial tests how well decitabine and cedazuridine (dec-c) works in combination with venetoclax in treating acute myeloid leukemia (aml) in patients whose aml has come back after a period of improvement (relapse) after a donor stem cell transplant. cedazuridine is in a class of medications called cytidine deaminase inhibitors. it prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. decitabine is in a class of medications called hypomethylation agents. it works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. venetoclax is in a class of medications called b-cell lymphoma-2 (bcl-2) inhibitors. it may stop the growth of cancer cells by blocking bcl-2, a protein needed for cancer cell survival. giving dec-c in combination with venetoclax may kill more cancer cells in patients with relapsed aml.

primary objective: i. to assess the effect of dec-c/venetoclax on the investigator-assessed composite complete remission (cr) rate (cr/complete remission with partial hematologic recovery \[crh\]/complete remission with incomplete hematologic recovery \[cri\]). secondary objectives: i. to assess the rate of partial response (pr) and morphologic leukemia free state (mlfs) following treatment with dec-c/venetoclax. ii. to assess the relapse free survival of patients treated with dec-c/venetoclax. iii. to assess overall survival of patients treated with dec-c/venetoclax. iv. to assess the safety and tolerability of dec-c/venetoclax in the post-hematopoietic cell transplant (hct) setting. v. to assess the rates of measurable residual disease negativity in patients achieving a cr. outline: patients receive venetoclax orally (po) daily for 28 days in a 28-day cycle. patients receive dec-c po daily on days 1-5 of a 28-day cycle. patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.

Eligibility criteria:
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