Phase 1B/2A Study of Weekly Decitabine and Venetoclax Treatment as Maintenance Therapy in High-Risk Myeloid Malignancy Patients Post Allograft Stem Cell Transplant
The goal of this interventional clinical trial is to determine if low doses of gentle chemotherapy after bone marrow transplant may prevent relapse and promote an increase in survival and decrease in side effects in participants with acute myeloid leukemia and myelodysplastic syndromes. The main question it aims to answer is whether or not providing a new, gentler way of administering chemotherapy will help control leftover cancer with minimal side effects. This treatment involves decitabine and venetoclax. Participants will receive standard post-transplant care. Participants will be administered decitabine once per week with normal transplant follow up visits, and then will take a venetoclax pill about 6 to 8 hours later. Participants will meet their study team at the beginning, midway, and at the end of the trial to receive bone marrow testing. Participants will receive treatment until either one year of therapy, relapse, or recurrent dose limiting toxicity (DLT) despite dose reduction.
• Diagnosis of Acute myeloid leukemia, MDS, MDS/AML with high-risk for post-transplant relapse identified by:
‣ Very high or high risk by CIBMTR Disease Risk Index (DRI) and/or adverse risk by ICC 2022 criteria and/or MDS/AML by ICC 2022 criteria.
⁃ Very high or high risk by CIBMTR DRI and/or by IPSS-M \> 0.510-12 and/or MDS/AML by ICC 2022 criteria.
• Bone marrow myeloblasts \<5% at pre-transplant bone marrow aspirate and biopsy with no circulating blasts.
• Participants must be planned for or have received alloSCT. Any conditioning regimen intensity or graft source (MRD/MUD/Haplo/UCB) is permitted.
• Participants must be 18 years of age or older.
• Total bilirubin \< 2.0 mg/dL (with the exception of participants with known Gilbert's syndrome, who should have direct bilirubin \< 2 × ULN).
• Creatinine clearance (CrCl) \> 30 ml/min.
• ECOG 0-1 performance status.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document and complete study related procedures.
• Participants may enroll prior to or after alloSCT. Participants should enroll no later than post transplant day 40, and the the following post-AlloHSCT inclusion criteria must be met in order to initiate the maintenance study treatment:
‣ Successful engraftment defined by absolute neutrophil count (ANC) of ≥500/ul and platelet count of ≥50,000/uL sustained for at least three consecutive days.
⁃ These criteria for engraftment should be met on or before Day +50.
⁃ No active infection
⁃ No GVHD ≥ overall grade II (Grade 1 GVHD of the skin acceptable).
⁃ Participants must continue to meet additional inclusion criteria
⁃ \<5% myeloblasts in a bone marrow aspirate with spicules, that is to be obtained, if all the above inclusion criteria are satisfied.