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Testing ziftomenib for relapsed or refractory acute myeloid leukemia

A Phase 1/2 First in Human Study of the Menin-MLL(KMT2A) Inhibitor KO-539 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Phase1; Phase2 Interventional Kura Oncology, Inc. · NCT04067336

This study is testing a new drug called ziftomenib to see if it can help people with relapsed or hard-to-treat acute myeloid leukemia feel better and fight their cancer.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment199 (estimated)
Ages18 Years and up
SexAll
SponsorKura Oncology, Inc. Industry-sponsored
Drugs / interventionschemotherapy, immunotherapy
Locations52 sites (Gilbert, Arizona and 51 other locations)
Trial IDNCT04067336 on ClinicalTrials.gov

What this trial studies

This clinical trial is a first-in-human, open-label study assessing ziftomenib, a menin-MLL(KMT2A) inhibitor, in patients with relapsed or refractory acute myeloid leukemia (AML). The study consists of a Phase 1 dose-escalation to determine the maximum tolerated dose and a Phase 2 assessment focusing on patients with NPM1-m AML. The trial aims to evaluate the safety, tolerability, and anti-leukemia activity of ziftomenib, providing critical data on its effectiveness in this challenging patient population.

Who should consider this trial

Good fit: Ideal candidates include adults with relapsed or refractory AML who have failed or are ineligible for standard therapies and have specific genetic mutations.

Not a fit: Patients with acute myeloid leukemia who do not have the required genetic mutations or who are not relapsed or refractory may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with difficult-to-treat forms of acute myeloid leukemia.

How similar studies have performed: Other studies have shown promise with similar approaches targeting menin-MLL interactions, indicating potential for success in this novel treatment.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

Patients with refractory or relapsed AML defined as the reappearance of ≥ 5% blasts in the bone marrow and who have also failed or are ineligible for any approved standard of care therapies, including HSCT.

1. Phase 1b:

   1. Patients with a documented lysine\[K\]-specific methyltransferase 2-rearrangement (KMT2A-r), or
   2. Patients with a documented nucleophosmin 1 mutation (NPM1-m)
2. Phase 2:

   a. Patients with a documented nucleophosmin 1 mutation (NPM1-m)
3. ≥ 18 years of age.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a life expectancy of at least 2 months.
5. Adequate liver and kidney function according to protocol requirements.
6. Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients may receive hydroxyurea to control and maintain white blood cell count prior to enrollment.
7. Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 180 days after the last dose of study treatment.
8. Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 90 days after the last dose of study treatment.

Key Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia.
2. Diagnosis of chronic myelogenous leukemia in blast crisis.
3. Donor lymphocyte infusion \< 30 days prior to study entry.
4. Clinically active central nervous system (CNS) leukemia.
5. Undergone HSCT and have not had adequate hematologic recovery.
6. Receiving immunosuppressive therapy post HSCT within 2 weeks of Cycle 1 Day 1.
7. Grade ≥ 2 active graft-versus-host disease (GVHD), moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.
8. Received chemotherapy immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug.
9. Not recovered to \< Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from all acute toxicities or deemed back to a stable baseline.
10. 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.
11. 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.
12. 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).
13. Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection.
14. Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within the past 6 months, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment.
15. Mean QTcF \>480 ms on triplicate ECG.
16. Major surgery within 4 weeks prior to the first dose of study treatment.
17. 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.

Where this trial is running

Gilbert, Arizona and 51 other locations

+2 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Malignant NeoplasmAcute Myeloid LeukemiaMixed Lineage LeukemiaMixed Lineage Acute LeukemiaAcute Leukemia of Ambiguous LineageMixed Phenotype Acute LeukemiaAMLHematological malignancy
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.