Phase 1B/2A Study of Weekly Decitabine and Venetoclax Treatment as Maintenance Therapy in High-Risk Myeloid Malignancy Patients Post Allograft Stem Cell Transplant
Benjamin Tomlinson
Summary
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.
Description
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While 60-80% patients can achieve remission, a high rate of relapse mandates consolidative treatment. Unfortunately, 40% of AML patients and 30% of myelodysplastic syndrome patients will relapse after alloSCT, and those who relapse after transplant exhibit poor outcomes. As such, prevention of post-transplant relapse remains a key interest. Maintenance therapy with low-intensity chemotherapy and/or targeted therapy is one strategy that holds promise to reduce post-transplant relapse, controlling residual subclinical dise…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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…
Interventions
- DrugVenetoclax
Venetoclax is a BCL2 inhibitor. It is administered at low doses and used in combination with other hypomethylating agents such as decitabine to manage participants with acute myeloid lymphoma who have undergone stem cell transplant. Participants will initiate therapy with decitabine that will be followed by venetoclax 400 mg oral 6-8 hours later. Participants will continue this dose each week. The venetoclax dose will be reduced to 100 mg once per week if the participant is being treated with posaconazole or voriconazole (strong CYP3A4 inhibitors) (considered dose equivalent to venetoclax 400 mg 1X/week). The venetoclax dose will be reduced 200 mg once per week if the participant is being treated with fluconazole or isavuconazole (moderate CYP3A4 inhibitors) (considered dose equivalent to venetoclax 400 mg 1X/week). This clinical trial is administering venetoclax well below the current FDA approved dosing.
- DrugDecitabine
Decitabine is a hypomethylating agent. It is administered at low doses and used in combination with venetoclax to manage participants with acute myeloid lymphoma who have undergone stem cell transplant. Participants initiate therapy with 5 mg/m2 decitabine subcutaneous every week followed by venetoclax.
Locations (2)
- Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer CenterCleveland, Ohio
- University Hospitals Seidman Cancer, Case Comprehensive Cancer CenterCleveland, Ohio