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
Uma Borate
Lead sponsor
Ohio State University Comprehensive Cancer Center
Sponsor institution