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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Banner MD Anderson Cancer Center
  Gilbert, Arizona, United States Recruiting
• University of California, Fresno
  Clovis, California, United States Recruiting
• University of California, San Diego
  La Jolla, California, United States Recruiting
• Cedars-Sinai Medical Center
  Los Angeles, California, United States Recruiting
• University of California, Los Angeles
  Los Angeles, California, United States Recruiting
• University of California, Irvine
  Orange, California, United States Recruiting

+86 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Kura Medical Information
• Email: medinfo@kuraoncology.com
• Phone: 844-KURAONC (844-587-2662)

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• PBSS1113 with azacitidine for AML and higher-risk MDS

  This study tests PBSS1113 together with azacitidine to see if it is safe and may help people with AML or higher-risk MDS who are newly diagnosed and not fit for intense chemotherapy or who have relapsed/refractory disease.

  Recruiting Phase 1/2 Chaser Therapeutics, Inc. · Hangzhou, Zhejiang · NCT07761533

• Caris Chromoseq data collection for AML, MDS, and MPN

  This study tests how well the Caris Chromoseq assay helps categorize risk in patients with AML, MDS, or MPN compared with standard tests.

  Recruiting Caris Science, Inc. · Phoenix, Arizona · NCT07680868

• Venetoclax TDM in newly diagnosed AML: exposure and prognosis

  This study checks if measuring venetoclax levels and adjusting treatment helps people with newly diagnosed AML who are getting VEN-AZA.

  Recruiting The First Affiliated Hospital of Soochow University · Suzhou · NCT07670130

• CAR-T cells targeting CD33 and CLL1 for relapsed or refractory AML

  A one-arm early-stage trial tests whether a patient’s own engineered CAR-T cells (ICG415) can be safely given after conditioning chemotherapy to see if they can help adults with relapsed or refractory AML.

  Recruiting at 2 sites Phase 1 iCell Gene Therapeutics · Nanchang, Jiangxi and 1 other locations · NCT07668557

• Ziftomenib for relapsed/refractory NPM1-mutated AML in Japanese adults

  This study will test whether ziftomenib can help adults with relapsed or refractory NPM1-mutated AML who have few other options.

  Recruiting at 15 sites Phase 2 Kyowa Kirin Co., Ltd. · Chiba and 19 other locations · NCT07623616

• VABu Conditioning for elderly AML patients undergoing stem cell transplant

  This trial tests a VABu conditioning regimen to see if it helps older AML patients before allogeneic stem cell transplantation.

  Recruiting Phase 2/3 The First Affiliated Hospital of Soochow University · Suzhou, Jiangsu · NCT07583888

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.