Ziftomenib for the Treatment of Patients With NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia Not Eligible for Standard Therapy
Frontline Ziftomenib in NPM1-Mutated or KMT2A-Rearranged Acute Myeloid Leukemia in Patients Not Eligible for Intensive Induction or Other Therapy
2 other identifiers
interventional
70
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 9, 2025
CompletedFirst Posted
Study publicly available on registry
April 16, 2025
CompletedStudy Start
First participant enrolled
April 10, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
March 13, 2026
March 1, 2026
1.7 years
April 9, 2025
March 11, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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.
After 6 cycles of treatment (cycle length = 28 days)
Secondary Outcomes (10)
Rate of transfusion independence
Up to 24 months
CR rate
Up to 24 months
Composite CR (CRc) rate
Up to 24 months
CRc with negative measurable residual disease
Up to 24 months
Overall response rate
Up to 24 months
- +5 more secondary outcomes
Study Arms (1)
Treatment (ziftomenib)
EXPERIMENTALPatients receive ziftomenib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo cytoreduction therapy with hydroxyurea up to end of cycle 1, cytarabine within 7 days of starting treatment, or leukapheresis within 7 days of treatment to reduce white blood cell count to =\< 10,000/uL. Additionally, patients undergo ECHO or MUGA at screening and bone marrow biopsy and/or aspiration and blood sample collection throughout the study.
Interventions
Undergo blood sample collection
Undergo bone marrow biopsy and/or aspiration
Given cytarabine
Given hydroxyurea
Undergo leukapheresis
Undergo MUGA
Given PO
Eligibility Criteria
You may qualify if:
- 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 performed locally
- Patients ineligible or unwilling to receive standard of care induction therapy, such as 7+3, hypomethylating agent, venetoclax, or other standard of care (SOC) regimens with ineligibility defined by the following:
- ≥ 75 years of age with both of the following;
- Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hours urine collection
- Subject must have adequate liver function as demonstrated by aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN) and alanine aminotransferase (ALT) ≤ 3.0 x ULN (unless considered due to leukemic organ involvement) OR
- ≥ 18 to 74 years of age with at least one of the following co-morbidities:
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3;
- Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction ≤ 50% or chronic stable angina;
- Diffusion capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%;
- Creatinine clearance ≥ 30 mL/min to \< 45 ml/min;
- Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 x ULN;
- Venous thromboembolism benefitting from prolonged anticoagulation or presence of prosthetic heart valve or any indication for therapeutic anticoagulation with a single agent
- +5 more criteria
You may not qualify if:
- 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
- Treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450-isozyme 3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient
- Detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen indicative of active infection. Patients with controlled disease will not be excluded from study enrollment
- Pre-existing disorder predisposing the patient to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML)
- Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection
- Mean Fridericia's formula-corrected QT interval (QTcF) \> 480 ms on triplicate electrocardiogram (ECG)
- Any psychiatric illness that prevents patient from informed consent process
- Women who are pregnant or lactating. All female patients with reproductive potential must have a negative serum pregnancy test within 72 hours prior to starting treatment
- Participants requiring dual antiplatelet therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Uma Boratelead
- Kura Oncology, Inc.collaborator
Study Sites (1)
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Uma M Borate, MBBS, MD, MSc
Ohio State University Comprehensive Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
April 9, 2025
First Posted
April 16, 2025
Study Start
April 10, 2026
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
March 13, 2026
Record last verified: 2026-03