Safety and Efficacy of Dual Menin and FLT3 Inhibition in Patients With Relapsed/Refractory FLT3- Mutated Acute Myeloid Leukemia Containing a Concurrent MLL-Rearrangement or NPM1 Mutation: A Phase I (Ph I) Study of SNDX-5613 + Gilteritinib
Uma Borate
Summary
This phase I trial tests the safety, side effects, and best dose of SNDX-5613 and gilteritinib for treating patients with acute myeloid leukemia that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory) and has a mutation in the FLT3 gene along with either a mutation in the NMP1 gene or a type of mutation called a rearrangement in the MLL gene. SNDX-5613 is in a class of medications called menin inhibitors. It works by blocking the action of mutated MLL and NMP1 proteins that signal cancer cells to multiply. Gilteritinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of mutated FLT3 proteins that signal cancer cells to multiply. Giving SNDX-5613 with gilteritinib may be safe, tolerable and/or effective in treating patients with relapsed/refractory FLT3 mutated acute myeloid leukemia.
Description
PRIMARY OBJECTIVE: I. To determine the safety of revumenib (SNDX-5613) + gilteritinib. SECONDARY OBJECTIVES: I. To determine the preliminary efficacy of SNDX- 5613+ Gilteritinib. EXPLORATORY OBJECTIVES: I. To perform pharmacokinetic and pharmacodynamics assessments of the study drug combination. OUTLINE: This is a dose-escalation study. Patients receive SNDX-5613 orally (PO) twice per day (BID) and gilteritinib PO once per day (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiogram (ECHO…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study * Age ≥ 18 years at the date of signing the informed consent form (ICF) * Morphologically confirmed diagnosis of the following based on 2022 World Health Organization (WHO) classification: * Relapsed or Refractory Acute Myeloid Leukemia with the following: * Refractory disease classified as having received 2 cycles of intensive induction or 2 cycles of hypomethylating agent (HMA) + Venetoclax with persistent disease of ≥ 5% blasts in the bone marrow and/or reappearance of peripheral blas…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Aspiration and Biopsy
Undergo bone marrow aspiration and biopsy
- DrugGilteritinib
Given PO
- DrugRevumenib
Given PO
- ProcedureEchocardiography Test
Undergo ECHO
- ProcedureMultigated Acquisition Scan
Undergo MUGA
Locations (3)
- UNC Hospitals, University of North Carolina at Chapel HillChapel Hill, North Carolina
- Ohio State University Comprehensive Cancer CenterColumbus, Ohio
- University of PennsylvaniaPhiladelphia, Pennsylvania