A Phase I/II Study of Gilteritinib and Momelotinib for Patients With Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia

Description

Primary Objectives

* Phase I: To establish the minimum safe and biologically-effective dose of momelotinib in combination with gilteritinib in relapsed/refractory FLT3-mutated AML
* Phase II: To determine the modified CRc rate of the regimen, including complete remission (CR), CR with incomplete hematologic recovery (CRi) or morphologic leukemia free state (MLFS)

Secondary Objectives

* To assess other efficacy endpoints (CR rate, measurable residual disease negativity by flow cytometry and FLT3 PCR, relapse-free survival, overall survival)
* To assess proportion of participants proceeding to allogeneic hematopoietic stem cell transplantation
* To determine the safety of the combination regimen

Exploratory Objectives

* To evaluate the impact of baseline genomic alterations on response and survival of the combination regimen
* To determine the impact of baseline FLT3 allelic ratio on response and survival
* To evaluate the pharmacokinetics (e.g. AUC, Cmax, Tmax and half-life) of momelotinib in the combination regimen
* To evaluate changes in circulating cytokine levels in response to treatment
* To evaluate inhibition of FLT3 signaling and inhibition of JAK/STAT signaling pathways
* To evaluate other biomarkers associated with response and resistance to the combination regimen