This phase II MyeloMATCH treatment trial compares ASTX727 with standard duration versus shorter duration of venetoclax for the treatment of newly diagnosed acute myeloid leukemia (AML). ASTX727 is a combination of decitabine and cedazuridine. 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. 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. 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. Shorter duration venetoclax may be as effective as standard duration venetoclax when given with ASTX727 for the treatment of newly diagnosed AML.
Participants must have been registered to the MYELOMATCH Master Screening and Reassessment Protocol prior to consenting to this study. Participants must have been assigned to this clinical trial via MATCHBox prior to registration to this study.
Note: Pre-enrollment/diagnosis labs must have already been performed under MYELOMATCH
Participants must have newly diagnosed, untreated acute myeloid leukemia (AML) defined by
Having ≥ 20% blasts in the bone marrow and/or peripheral blood or
None
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Decitabine and Cedazuridine
DrugGiven PO
Venetoclax
DrugGiven PO
Minimal residual disease (MRD) negative complete remission (CR)
Will compare the proportion of participants who achieve an MRD negative CR at 180 days between the two arms, including standard-of-care arm with 28 day duration of venetoclax in combination with ASTX727 versus experimental arm with 14 day duration of venetoclax in combination with ASTX727, using hierarchical testing to first assess that 14 days of venetoclax is not more than 12% worse than 28 days of venetoclax and if found to be non-inferior, test whether 14 days of venetoclax results in higher MRD negative CR at 180 days compared to the 28-day arm. Defined as from date of randomization the first of the following failure events: death from any cause, off protocol therapy without MRD negative CR, relapse from MRD negative CR, off protocol therapy without assessment of CR, off protocol therapy without assessment of MRD. Will be analyzed using intent-to-treat principles among eligible participants.
Event free survival
Will be estimated using the Kaplan-Meier method. Response per 2022 European Leukemia Network (ELN) risk will be tabulated and exact 95% confidence intervals will be calculated.
Relapse free survival
Defined only for participants achieving CR, CRi, or CRh. Will be estimated using the Kaplan-Meier method. Response per 2022 ELN risk will be tabulated and exact 95% confidence intervals will be calculated.
Overall survival
Will be estimated using the Kaplan-Meier method. Response per 2022 ELN risk will be tabulated and exact 95% confidence intervals will be calculated.
Incidence of adverse events (AEs)
All AEs will be tabulated by Medical Dictionary for Regulatory Activities system organ class and preferred term. Grade 3-4 AE rates, serious AE rates, and rates of AEs leading to discontinuation between arms will be compared and risk will be reported with 95% confidence intervals (CI). Cumulative incidence of AEs of special interest (AESIs) will be calculated in each arm using the Kaplan-Meier method. Relative risk and risk difference of AESIs between arms at 180 days will be reported with 95% CI.
Click on the lead sponsor to view all of their trials.