Frontline Ziftomenib in NPM1-Mutated or KMT2A-Rearranged Acute Myeloid Leukemia in Patients Not Eligible for Intensive Induction or Other Therapy
Uma Borate
Summary
This phase II trial tests how well ziftomenib works in treating patients with NPM1 mutated or KMT2A rearranged acute myeloid leukemia (AML) and are not eligible to receive standard therapy. AML is often due to genetic changes in the cancer cells, including mutations in the NPM1 gene and rearrangements involving the KMT2A gene. These mutations result in activation of the menin pathway. Menin is a type of protein in the body that helps to regulate some of the naturally occurring processes in the body, but can also be involved in some types of cancers. Ziftomenib blocks this menin pathway and may prevent the cancer cells from continuing to grow. Giving ziftomenib may kill more cancer cells in patients with NPM1 mutated or KMT2A rearranged AML that are not eligible to receive standard therapy.
Description
PRIMARY OBJECTIVE: I. To determine the efficacy of ziftomenib in treatment-naïve patients with KMT2A-rearranged (r) and NPM1-mutated (m) AML who are not candidates for standard therapy, with primary endpoint of complete remission (CR) + CR/response with hematologic improvement (CRh), assessed after 6 cycles of treatment using the best response achieved in that time. SECONDARY OBJECTIVES: I. To determine rates of transfusion independence for 8- and 16-week periods. II. To determine response including CR, composite CR (CRc) (CR + CRh + CR with incomplete blood count recovery \[CRi\] + CR with…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study * Morphologically confirmed diagnosis of the following based on 2022 World Health Organization (WHO) Classification: * Treatment-naïve acute myeloid leukemia * KMT2A rearrangement (defined as KMT2A translocations) OR NPM1 mutation (defined as NPM1 mutation resulting in cytoplasmic localization, or NPM1c) OR other mutations that have been shown to exhibit sensitivity to menin inhibition. Mutation status will be known from initial diagnosis using standard of care testing, which can be perform…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Aspiration
Undergo bone marrow biopsy and/or aspiration
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy and/or aspiration
- DrugCytarabine
Given cytarabine
- ProcedureEchocardiography Test
Undergo ECHO
- DrugHydroxyurea
Given hydroxyurea
- ProcedureLeukapheresis
Location
- Ohio State University Comprehensive Cancer CenterColumbus, Ohio