This phase I/II trial studies the side effects and best dose of momelotinib and to see how well it works in combination with gilteritinib in treating patients with acute myeloid leukemia (AML) with a FLT3 mutation that has that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Momelotinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells. Gilteritinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving momelotinib in combination with gilteritinib may work better in treating patients with relapsed or refractory FLT3-mutated AML.
Additional locations may be listed on ClinicalTrials.gov for NCT06235801.
Locations matching your search criteria
United States
Texas
Houston
M D Anderson Cancer CenterStatus: Active
Contact: Nicholas Short
Phone: 713-563-4485
PRIMARY OBJECTIVES:
I. To establish the minimum safe and biologically-effective dose of momelotinib in combination with gilteritinib in relapsed/refractory FLT3-mutated AML. (Phase I)
I. To determine the modified composite complete remission (CRc) rate of the regimen, including complete remission (CR), CR with incomplete hematologic recovery (CRi) or morphologic leukemia free state (MLFS). (Phase II)
SECONDARY OBJECTIVES:
I. To assess other efficacy endpoints (CR rate, measurable residual disease negativity by flow cytometry and FLT3 polymerase chain reaction [PCR], relapse-free survival, overall survival).
II. To assess proportion of patients proceeding to allogeneic hematopoietic stem cell transplantation.
III. To determine the safety of the combination regimen.
EXPLORATORY OBJECTIVES:
I. To evaluate the impact of baseline genomic alterations on response and survival of the combination regimen.
II. To determine the impact of baseline FLT3 allelic ratio on response and survival.
III. To evaluate the pharmacokinetics (e.g. area under the curve [AUC], maximum concentration [Cmax], time to peak drug concentration [Tmax] and half-life) of momelotinib in the combination regimen.
IV. To evaluate changes in circulating cytokine levels in response to treatment.
V. To evaluate inhibition of FLT3 signaling and inhibition of janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways.
VI. To evaluate other biomarkers associated with response and resistance to the combination regimen.
OUTLINE: This is a phase I, dose-escalation study of momelotinib in combination with gilteritinib, followed by a phase II study.
Patients receive momelotinib orally (PO) days 1-35 of cycles 1 and days 1-28 of subsequent cycles. Patients receive gilteritinib PO days 8-35 of cycle 1 and days 1-28 of subsequent cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo bone marrow biopsy and aspiration and blood sample collection during screening and on the trial.
After completion of study treatment, patients are followed up every 6 months until death.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorNicholas Short
