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.
Signed informed consent must be obtained prior to participation in the study
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 performed locally
≥ 75 years of age with both of the following;
Diagnosis of acute promyelocytic leukemia
Diagnosis of chronic myelogenous leukemia in blast crisis
Clinically active central nervous system (CNS) leukemia
Prior treatment for AML except for hydroxyurea and/or cytarabine used for control of leukocytosis
Single group
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow biopsy and/or aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy and/or aspiration
Cytarabine
DrugGiven cytarabine
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Hydroxyurea
DrugGiven hydroxyurea
Leukapheresis
Procedure/SurgeryUndergo leukapheresis
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Questionnaire Administration
Other interventionAncillary studies
Ziftomenib
DrugGiven PO
Complete remission (CR) plus CR/response with hematologic improvement
Will be assessed after 6 cycles of treatment using the best response achieved in that time. Will be calculated in each arm for the efficacy analysis population and reported along with two-sided 95% exact binomial confidence limits, in a modified intent-to-treat analysis.
Rate of transfusion independence
Transfusion independence is defined as the proportion of subjects without transfusions during any consecutive 8 weeks (56 days) starting from Study Day 1 and has correlated with palliative benefits in patients with AML \[19\]. The major criteria for judging response will include physical examination and laboratory evaluation.
CR rate
Will also be calculated in the primary efficacy analysis cohort along with 95% exact binomial confidence intervals.
Composite CR (CRc) rate
Will also be calculated in the primary efficacy analysis cohort along with 95% exact binomial confidence intervals.
CRc with negative measurable residual disease
Will also be calculated in the primary efficacy analysis cohort along with 95% exact binomial confidence intervals.
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Uma Borate
Lead sponsor
Ohio State University Comprehensive Cancer Center
Sponsor institution
Kura Oncology, Inc.
Collaborator
