Ruxolitinib With Azacitidine Maintenance for the Treatment of Patients With Acute Myeloid Leukemia Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation

Inclusion Criteria: * PART A: Willingness to provide written informed consent before any study-specific procedures or interventions are performed. For participants unable to independently provide consent, a legally authorized representative (LAR) must provide consent * PART A: Age ≥ 18 years, at the time of consent * PART A: All types and categories of AML, as defined by World Health Organization (WHO) 2022, excluding acute promyelocytic leukemia (APL) * PART A: In complete remission (CR) or complete remission with incomplete blood count recovery (CRi) after induction of remission for transition to transplant by European LeukemiaNet 2022 Risk Stratification (ELN 2022) * PART A: Planned alloHSCT with granulocyte colony-stimulating factor mobilized peripheral blood stem cells (PBSCs) and pre transplant conditioning disease status assessment of CR or CRi, as defined by ELN 2022 criteria * PART A: Patient is at high risk for relapse based on cytogenetics, MRD by next generation sequencing (NGS), and/or ELN 2022 definition of adverse risk disease per the opinion of the treating physician * PART A: Patients must have an unrelated PBSC donor meeting study donor selection requirements * PART A: Only RIC or NMA conditioning must be plan and patient is not a candidate for myeloablative conditioning (MAC). Post-transplant cyclophosphamide / tacrolimus / mycophenolate mofetil (PTCy/Tac/MMF) GVHD prophylaxis is planned with PTCy at 25 mg/kg/day on Day +3 and Day +4 post-HSCT * Permitted conditioning regimens (per institutional protocol) * Reduced-intensity conditioning: * Fludarabine/ melphalan * Dose reduction of melphalan to 100 rather than 140 are permitted at discretion of treating physician * Non-Myeloablative Conditioning: * Fludarabine/ busulfan/ total-body irradiation (TBI) * Fludarabine/ TBI * PART A: Backup graft donor (meeting study donor selection requirements) identified and ready for cases of graft failure * PART A: Karnofsky performance status (KPS) ≥ 50% * PART A: Direct bilirubin ≤ 3 × upper limit of normal (ULN) within 7 days prior to start of conditioning. Patients with leukemic involvement or Gilbert's Syndrome must have a direct bilirubin of ≤ 2 x ULN within 7 days of start of conditioning * PART A: Creatinine clearance \> 30 mL/min, calculated by the Cockcroft-Gault formula or measured by 24-hour urine collection * PART A: Willingness to receive infusion of SOC blood products * PART A: Evidence of chronic hepatitis B virus (HBV) infection (i.e., hepatitis B virus surface antigen \[HBsAg\]-positive with undetectable or low HBV deoxyribonucleic acid \[DNA\]) in the absence of HBV therapy, or serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and hepatitis B virus core antibody \[anti-HBc-positive\]) is permitted but patient must agree to appropriate institutional guideline prophylaxis * PART A: History of hepatitis C virus (HCV) infection is permitted given prior curative treatment or undetectable HCV viral load by serology or polymerase chain reaction (PCR) testing * Patients who are HCV antibody (Ab) seropositive but HCV ribonucleic acid (RNA) negative due to prior treatment or natural resolution are eligible * PART A: For persons of child-bearing potential (PCBP), a negative pregnancy test within ≤ 7 days of start of conditioning * PART A: Ruxolitinib may have adverse effects on a fetus in utero. Furthermore, it is not known if either drug agent has transient adverse effects on the composition of sperm. PCBP and participants who produce viable sperm must be willing to comply with study requirements for contraception starting at start of conditioning through 120 days after discontinuation of study treatment. Should a participant or participant's sexual partner become pregnant or suspect a pregnancy while participating in this study, the individual should inform their treating physician immediately * PART A: It is unknown whether ruxolitinib, or its metabolites, are excreted in human milk. Since many drugs are excreted in human milk, and because of the potential for serious adverse reactions in the nursing infant, patients must agree to not breast-feed for the entire 2 years of the study to be eligible for enrollment * PART B: Absolute neutrophil count (ANC) ≥ 1,000/μL, measured twice approximately 48 hours apart, within 7 days prior to C2D1, in the absence of granulocyte colony-stimulating factor (G-CSF) treatment during this 7-day period * PART B: Platelet count ≥ 50,000/μL, measured twice approximately 48 hours apart, within 7 days prior to C2D1, in the absence of platelet transfusions or growth factor therapies that increase platelet counts during this 7 day period * PART B: Hemoglobin \> 8 g/L within the 7 days prior to C2D1, regardless of transfusion support * PART B: Day +30 (+/- 5 days) chimerism of ≥ 70% donor CD3+ cells and 100% donor CD33+ cells * PART B: For PCBP, a negative pregnancy test within 72 hours prior to C2D1 * DONOR: Donor is willing and able to donate * DONOR: Unrelated donor with a 7/8 or 8/8 match at human leukocyte antigen (HLA)-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be willing to donate peripheral blood stem cells * DONOR: Age 18-35 at the time of workup request for PBSC donation * DONOR: Meet the donor registries' medical suitability requirements for PBSC donation * DONOR: Must undergo screening, testing, and determination of eligibility according to current Food and Drug Administration (FDA) requirements as defined in 21 Code of Federal Regulations (CFR) 1271 Subpart C and applicable guidance documents. Donors will be tested using kits that are FDA licensed, approved, or cleared for human cell and tissue/tissue-product donor screening. Sample testing will be performed at Clinical Laboratory Improvement Amendments (CLIA) certified laboratories * DONOR: Must agree to donate PBSC * DONOR: Must have the ability to give informed consent accord…

Reproduced word-for-word from the public registry record — the study team can answer questions about it.