This phase II trial compares induction and consolidation therapy with fludarabine, cytarabine, idarubicin, and venetoclax to cytarabine and daunorubicin induction and cytarabine consolidation for the treatment of acute myeloid leukemia (AML). Patients with AML often receive induction and consolidation therapy. Induction therapy is given first to get the patient's AML under control (remission). Consolidation therapy is given after the cancer has disappeared following the initial therapy. Consolidation therapy is used to kill any cancer cells that may be left in the body. Chemotherapy drugs, such as fludarabine, cytarabine, idarubicin, and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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. Giving fludarabine, cytarabine, idarubicin, and venetoclax for induction and consolidation therapy may be more effective in treating AML.
Ability to comprehend the investigational nature of the study and provide written informed consent
Age 18 to ≤ 65 years (yrs), at the time of consent
All gender identities, races, or ethnicities are eligible
Newly documented, previously untreated diagnosis of AML or myelodysplastic syndrome (MDS) with marrow blasts ≥ 10%, in agreement with 2022 European LeukemiaNet criteria (ELN22)
Documented t(15;17) (acute promyelocytic leukemia [APL]), and/or mutation(s) to FLT3 ITD or core binding factor (CBF). Point mutations within the tyrosine kinase domain (FLT3 TKD) are allowed
Another active malignancy within the previous 5 years, except treated early stage carcinomas of the skin, or at the investigator's discretion
Known, active central nervous system (CNS) involvement with AML
Recent and significant medical interventions, such as major surgery within 28 days of start of treatment
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Cytarabine
DrugGiven IV
Daunorubicin
DrugGiven IV
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Fludarabine
DrugGiven IV
Idarubicin
DrugGiven IV
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA scan
Questionnaire Administration
Other interventionAncillary studies
Venetoclax
DrugGiven PO
Percentage of participants achieving measurable residual disease negative composite complete remission (CRc-MRD-)
Will be defined as the achievement of both measurable disease negative (MRD-) by multiparameter flow cytometry and complete response (CR), CR with partial hematologic recovery (CRh), or CR with incomplete blood count recovery (CRi). Participants who do not qualify as efficacy-evaluable (usually due to early death or withdrawal because of toxicity) will be considered non-responders. A point estimate and 95% exact confidence interval (CI) for CRc MRD- will be computed for each arm (and time point) separately and the CRc MRD- rate will be statistically compared across arms with Fisher's exact test at 3 timepoints: end of induction, end of the first consolidation cycle, and end of treatment. A Hochberg multiplicity adjustment will be applied to the p-values from these 3 Fisher exact tests to control the family wise error rate (at α=0.05) for between-arm comparisons of the primary endpoint. CRc MRD- status at each of the above-specified time points will be modeled with logistic regression.
Percentage of participants achieving CR
Will be computed for each arm separately in both the safety set and the efficacy set. Will be presented with a point estimate and exact binomial 95% CI. will also be modeled with logistic regression with baseline patient and disease features as predictors and results considered hypothesis-generating.
Percentage of participants achieving composite complete remission (CRc)
CRc will be defined as the achievement of CR, CRh, or CRi. Will be computed for each arm separately in both the safety set and the efficacy set. Will be presented with a point estimate and exact binomial 95% CI. will also be modeled with logistic regression with baseline patient and disease features as predictors and results considered hypothesis-generating.
Percentage of participants achieving an overall response (ORR)
Will be defined as the proportion of participants who attain a partial remission (PR) or better (i.e., CR, CRh, CRi, morphologic leukemia-free state, or PR) after receiving study treatment. Will be computed for each arm separately in both the safety set and the efficacy set and presented with point estimate and exact binomial 95% CI. Will also be modeled with logistic regression with baseline patient and disease features as predictors and results considered hypothesis-generating.
Incidence of treatment-emergent grade ≥ 3 adverse events (AEs)
Will be assessed using Common Terminology Criteria for Adverse Events version 5.0. The incidence of specific grade ≥ 3 AEs will be reported with frequencies and percentages, at the overall participant level and by grade, attribution (i.e., a separate table for treatment-related AEs), and seriousness (i.e., separate tables for serious adverse events).
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OHSU Knight Cancer Institute
Lead sponsor
Oregon Health and Science University
Collaborator
