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.
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)
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 blasts
FLT-3 mutated disease of the ITD or TKD subtype, AND
Diagnosis of acute promyelocytic leukemia
Diagnosis of extra-medullary acute myeloid leukemia (AML) based on WHO 2022 classification or myeloid sarcoma
Suspected central nervous system (CNS) involvement. Patients with history of cerebrospinal fluid (CSF) involvement must either have documented CSF clearance prior to treatment initiation or be receiving active treatment for CNS involvement
Participants with history of adequately treated malignancy for which no anticancer systemic therapy (namely chemotherapy, radiotherapy or surgery) is ongoing or required during the course of the study
Single group
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration and Biopsy
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Gilteritinib
DrugGiven PO
Revumenib
DrugGiven PO
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Incidence of hematologic adverse events (AEs)
Adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The toxicity data captured will include type, frequency, grade, severity, timing of onset, duration and relationship to study drug. Frequency tables will be used to summarize the AE data, where the number of patients with different types of AE will be tabulated by toxicity grade, counting only the highest grade of a certain type of AE occurred to the same patient. All adverse events regardless of attribution as well as those treatment- related AEs will be summarized.
Incidence of non-hematologic adverse events
Adverse events will be graded according to CTCAE v5.0. The toxicity data captured will include type, frequency, grade, severity, timing of onset, duration and relationship to study drug. Frequency tables will be used to summarize the AE data, where the number of patients with different types of AE will be tabulated by toxicity grade, counting only the highest grade of a certain type of AE occurred to the same patient. All adverse events regardless of attribution as well as those treatment- related AEs will be summarized.
Recommended phase 2 dose for drug combination
Will be determined based on the maximum tolerated dose in conjunction with pharmacokinetic and pharmacodynamic assessments.
Composite Complete Response Rate (CRc)
Will be calculated in the efficacy analysis population and reported along with two-sided 95% exact binomial confidence limits.
Overall Response Rate
Rate of CRc with Measurable Residual Disease Negativity
will be calculated in the efficacy analysis population and reported along with two-sided 95% exact binomial confidence limits.
Duration of response
Will be calculated among patients who achieve a response and estimated using the method of Kaplan-Meier.
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Uma Borate
Lead sponsor
Ohio State University Comprehensive Cancer Center
Sponsor institution
