Decitabine and Venetoclax Treatment as Maintenance Therapy in Patients Post Allograft Stem Cell Transplant
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorBenjamin Tomlinson
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of Acute myeloid leukemia, MDS, MDS/AML who requires and allogeneic stem cell transplant.
For AML and MDS/AML, bone marrow myeloblasts <5% at pre-transplant bone marrow sample with no circulating blasts. For MDS patients, pre-transplant bone marrow myeloblasts < 10%
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.
Disqualifiers
Other planned post-transplant maintenance therapy, such as FLT3-ITD targeting agents, as determined by the treating physician
Currently pregnant or breast-feeding. Females of childbearing (FOCBP) potential must have negative serum pregnancy test within 72 hours from treatment start. (NOTE: FOCBP is any biologic female, regardless of sexual or gender orientation, having undergone tubal ligation, or remaining celibate by choice, who has not undergone a documented hysterectomy or bilateral oophorectomy or has had a menses any time in the preceding 12 months (therefore not naturally post-menopausal for > 12 months)
Active infection
Uncontrolled concurrent malignancy
Trial design
Design model
Single group
Treatments tested in this trial
Venetoclax
DrugVenetoclax 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.
Decitabine
DrugDecitabine 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.
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: Low dose maintenance chemotherapyExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Safety as measured by dose limiting toxicities
The primary objective of this study will be to assess the safety of low dose decitabine/venetoclax in the post transplant setting. Safety will be defined in accordance with FDA guidance on development for new therapeutics in AML with the particular criteria to be considered as DLTs. The stopping criteria are described for the incidence of dose limiting toxicities that are at least possibly related to the study treatment. Using Bayesian toxicity monitoring with maximum DLT probability as 0.15, prior distribution (0.5, 0.5), maximum participants 20, minimum number of participants before stopping 9, cohort size 5, and posterior probability 0.8, the study will be paused for review if (2, 3, 4, 5) or more participants experiencing such Grade 4 events in (69, 11, 16, 20) participants, respectively.
Time frame
1 year after treatment2
Feasibility as measured by the rate of participants receiving planned treatment
The primary objective of this study will be to assess the feasibility of low dose decitabine/venetoclax in the post transplant setting. Feasibility will be defined as ≥ 80% of participants receiving ≥80% of planned decitabine/venetoclax doses, excluding participants removed from the study in the event of relapse.
Time frame
1 year after treatmentSecondary outcomes
1
Rate of relapse free survival
The secondary objective is to determine the effects of low dose decitabine/venetoclax on the one relapse free survival compared to CIBMTR historical Disease Risk Index (DRI) data. The CIBMTR Disease Risk Index (DRI) is a clinically validated tool to predict survival post-transplant survival. Relapse-free survival (RFS) is measured from the date of the stem cell infusion to the date of disease progression or the date of death, whichever occurs first; and is censored at the date of last followed for those alive without disease progression. Relapse will be defined as more than 5% blasts on bone marrow biopsy, or, in the case of myelodysplastic syndrome (MDS), any clinical change that in the treating physician's opinion triggers change in therapy and will be compared to historical CIBMTR controls for very high or high risk for relapse by CIBMTR Disease Risk Index (DRI).
Time frame
1 year after treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Benjamin Tomlinson
Lead sponsor
Case Comprehensive Cancer Center
Sponsor institution
Source ClinicalTrials.gov