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Ziftomenib with standard chemotherapy or venetoclax+azacitidine for newly diagnosed NPM1‑mutated or KMT2A‑rearranged AML

Phase 3 Randomized, Double-blind, Placebo-controlled Studies Assessing Ziftomenib in Combination With Either Standard of Care Nonintensive (Venetoclax+Azacitidine) or Intensive (7+3) Therapy in Patients With Untreated NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia

Phase 3 Interventional Kura Oncology, Inc. · NCT07007312

This trial will test whether adding ziftomenib to standard chemotherapy (7+3) or to venetoclax plus azacitidine helps adults with newly diagnosed NPM1‑mutated or KMT2A‑rearranged AML achieve better remissions and longer survival.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1300 (estimated)
Ages18 Years and up
SexAll
SponsorKura Oncology, Inc. Industry-sponsored
Locations53 sites (Gilbert, Arizona and 52 other locations)
Trial IDNCT07007312 on ClinicalTrials.gov

What this trial studies

This program comprises two randomized, double‑blind, placebo‑controlled phase 3 studies testing ziftomenib added to standard nonintensive therapy (venetoclax + azacitidine) in older or medically unfit patients with NPM1‑mutated AML, and added to intensive induction (7+3), consolidation, and maintenance in medically fit patients with NPM1‑mutated or KMT2A‑rearranged AML. Patients are randomized to receive ziftomenib or placebo together with the appropriate standard‑of‑care regimen, and the intensive study includes multiple maintenance arm permutations. Key outcomes include remission rates and overall survival, along with safety and tolerability monitoring. The double‑blind design aims to isolate the effect of ziftomenib on clinical outcomes.

Who should consider this trial

Good fit: Adults (≥18 years) with newly diagnosed AML who have an NPM1 mutation or a KMT2A rearrangement and meet either the nonintensive (older/medically unfit) or intensive (medically fit) treatment eligibility criteria are ideal candidates.

Not a fit: Patients without NPM1 mutations or KMT2A rearrangements, those with relapsed/refractory disease, or patients unable to receive the required intensive or nonintensive standard therapies are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, adding ziftomenib could increase remission rates and extend survival by targeting the menin pathway in patients with these specific genetic subtypes of AML.

How similar studies have performed: Early‑phase trials of menin inhibitors, including ziftomenib, have shown promising single‑agent responses in NPM1‑mutated and KMT2A‑rearranged AML, but phase 3 randomized data are still needed.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

The following criteria apply to both the Nonintensive Therapy Study and the Intensive Therapy Study unless otherwise noted:

* Age ≥18 years at time of signing the informed consent form.
* Diagnosis of AML per the 2022 WHO Classification of Hematolymphoid Tumors (5th Edition).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Adequate liver and kidney function according to protocol requirements.
* A female of childbearing potential must agree to use adequate contraception from the time of screening through 180 days following the last dose of study intervention. A male with a female partner of childbearing potential must agree to use abstinence or adequate contraception from the time of screening through 90 days following the last dose of study intervention.
* NONINTENSIVE THERAPY STUDY ONLY (VEN+AZA):

  1. Documented NPM1-m.
  2. Patients considered ineligible for Intensive Therapy defined by the following:

     * i. Age ≥75, OR
     * ii. Age \<75 with an ECOG performance status of 2 or cardiac, renal, or hepatic impairment per protocol criteria.
* INTENSIVE THERAPY STUDY ONLY (7+3):

  1. Documented NPM1-m or KMT2A-r (KMT2A-r patients with a partial tandem duplication are not eligible).
  2. Documented FLT3 wild-type or ITD ratio \<0.05 OR ineligible to receive FLT3-targeted therapy (medically ineligible or mutation in which FLT3 inhibition is not SOC). Lack of access to an FLT3 inhibitor is not considered "ineligible" for FLT3-targeted therapy.
  3. Ejection fraction of ≥50%.
  4. Fit for Intensive Therapy per Investigator opinion.

Key Exclusion Criteria:

* Prior therapy for AML (except hydroxyurea or leukapheresis for WBC control).
* Diagnosis of acute promyelocytic leukemia (APL), blast phase chronic myeloid leukemia, or isolated myeloid sarcoma.
* Known history of BCR-ABL mutation.
* History of other active concurrent malignancies prior to study entry except:

  1. Basal cell skin cancer or localized squamous cell cancer of the skin
  2. Previous malignancy confined and locally resected (or treated with other modalities) with curative intent
  3. Prostate or breast cancer receiving adjuvant hormonal therapy.
* Active central nervous system (CNS) involvement by AML.
* Clinical signs/symptoms of leukostasis or white blood cells (WBC) \>25×10\^9/L prior to start of ziftomenib/placebo. Note: Hydroxyurea and/or leukapheresis are permitted to meet this criterion.
* Known uncontrolled HIV infection or known active hepatitis B virus, hepatitis C virus infection, or other uncontrolled infection.
* Uncontrolled intercurrent illness including but not limited to, cardiac illness as defined in the protocol.
* Women who are pregnant or lactating.

Where this trial is running

Gilbert, Arizona and 52 other locations

+3 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 Acute Myeloid LeukemiaAMLHematological malignancyKMT2ANPM1MeninAcute LeukemiaLeukemia
Last reviewed 2026-06-15 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.