Studies to Assess Ziftomenib in Combination With Ven+Aza or 7+3 in Patients With Untreated NPM1-m or KMT2A-r AML

NCT07007312
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Phase
Phase 3
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Recruitment status
Recruiting
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Participants
1,300
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Lead sponsor
Kura Oncology, Inc.
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Start date
2025-09-26
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Number of sites
115
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Summary
Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with eligible genetic alterations. Ziftomenib is a type of therapy known to target the menin pathway in cancer cells. This protocol has 2 separate studies that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) AML treatments in patients with certain genetic mutations who have not received any treatment for their AML. In the first study, the Nonintensive Therapy Study, older patients or those with serious medical problems will receive the SOC therapies venetoclax (ven) and azacitidine (aza), plus either ziftomenib or a placebo. In the second study, the Intensive Therapy Study, medically fit patients will receive (a) the SOC therapies cytarabine and daunorubicin, plus either ziftomenib or a placebo during a first treatment phase called induction, (b) cytarabine plus either ziftomenib or a placebo during a second treatment phase called consolidation, and (c) ziftomenib or a placebo during a third treatment phase called maintenance. The physician will determine which study is the appropriate treatment for the patient, but neither the patient nor their physician will know whether the patient has been assigned to receive ziftomenib or a placebo. This design is called "double-blinded".
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Short title
Studies to Assess Ziftomenib in Combination With Ven+Aza or 7+3 in Patients With Untreated NPM1-m or KMT2A-r AML
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Official title
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
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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2031-11-01
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First posted
2025-06-05
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Registry last updated
2026-08-20
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Primary completion date
2031-11-01
clinicaltrials.gov
Start date
2025-09-26
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Participants
1,300
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Participant count basis
Estimated
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Planned participants
1,300
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Protocol amendments
3
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Number of sites
115
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Kura Oncology, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT07007312
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ClinicalTrials.gov ID
NCT07007312
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Nonintensive Therapy Study: (Primary Endpoint for all countries): Overall survival (OS)

    Timeframe: Defined as the time from randomization to date of death from any cause, assessed up to 36 months after last patient inclusion

    OS

  2. Nonintensive Therapy Study: (Dual Primary Endpoint for US & US reference countries only): Complete remission (CR)

    Timeframe: Assessed up to 36 months after last patient inclusion

    CR rate per European Leukemia Network (ELN) 2022 criteria per Investigator assessment

  3. Intensive Therapy Study: (Primary Endpoint for all countries): Event-free survival (EFS)

    Timeframe: Defined as the time from randomization to treatment failure, hematologic relapse following CR, or death from any cause, whichever comes first, assessed up to 36 months after last patient inclusion

    EFS

  4. Intensive Therapy Study: (Dual Primary Endpoint for US & US reference countries only): Complete remission (CR) with bone marrow (BM) measurable residual disease (MRD) negativity in NPM1-m patients

    Timeframe: Assessed up to 36 months after last patient inclusion

    CR rate per ELN 2022 criteria per Investigator assessment with central BM MRD negativity

  1. Nonintensive Therapy Study: (EU & EU reference countries only): Complete remission (CR)

    Timeframe: Up to 36 months after last patient inclusion

    CR rate per ELN 2022 criteria per Investigator assessment

  2. Nonintensive Therapy Study: Bone marrow (BM) measurable residual disease (MRD) negativity

    Timeframe: Up to 36 months after last patient inclusion

    Central BM MRD negativity rate

  3. Nonintensive Therapy Study: Complete remission (CR) + complete remission with partial hematologic recovery (CRh)

    Timeframe: Up to 36 months after last patient inclusion

    CR + CRh rate per ELN 2022 criteria per Investigator assessment

  4. Nonintensive Therapy Study: Descriptive statistics of Adverse Events (AEs)

    Timeframe: From start of treatment to 28 days from last dose of ziftomenib or placebo

    Assessed by NCI-CTCAE v5.0

  5. Nonintensive Therapy Study: Area under the concentration-time curve (AUC) of ziftomenib and venetoclax

    Timeframe: During treatment for up to 36 months after last patient inclusion

    To characterize the AUC of ziftomenib and venetoclax

  6. Nonintensive Therapy Study: Trough concentration (Ctrough) of ziftomenib and venetoclax

    Timeframe: During treatment for up to 36 months after last patient inclusion

    To characterize the Ctrough of ziftomenib and venetoclax

  7. Nonintensive Therapy Study: Health-related patient-reported outcomes (PRO) assessments

    Timeframe: Up to 36 months after last patient inclusion

    Health-related quality of life (HRQoL) was evaluated by EORTC QLQ-C30 global health status/quality of life composite scale in all randomized participants. The QLQ-C30 is a cancer-specific, self-administered questionnaire that contains 30 questions, covering global, functional, and symptom scales. Scores range from 0 to 100. Higher scores on global and functional scales indicated better quality of life (QoL), while higher scores on the symptom scales indicated declining QoL.

  8. Intensive Therapy Study: (EU & EU reference countries only): Complete remission (CR) with bone marrow (BM) measurable residual disease (MRD) negativity in NPM1-m patients

    Timeframe: Up to 36 months after last patient inclusion

    CR rate per ELN 2022 criteria per Investigator assessment with central BM MRD negativity

  9. Intensive Therapy Study: Overall survival (OS)

    Timeframe: Defined as the time from randomization to date of death from any cause, up to 36 months after last patient inclusion

    OS

  10. Intensive Therapy Study: Descriptive statistics of Adverse Events (AEs)

    Timeframe: From start of treatment to 28 days from last dose of ziftomenib or placebo

    Assessed by NCI-CTCAE v5.0

  11. Intensive Therapy Study: Health-related patient-reported outcomes (PRO) assessments

    Timeframe: Up to 36 months after last patient inclusion

    Health-related quality of life (HRQoL) was evaluated by EORTC QLQ-C30 global health status/quality of life composite scale in all randomized participants. The QLQ-C30 is a cancer-specific, self-administered questionnaire that contains 30 questions, covering global, functional, and symptom scales. Scores range from 0 to 100. Higher scores on global and functional scales indicated better quality of life (QoL), while higher scores on the symptom scales indicated declining QoL.

  12. Intensive Therapy Study: Area under the concentration-time curve (AUC) of ziftomenib

    Timeframe: During treatment for up to 36 months after last patient inclusion

    To characterize the AUC of ziftomenib

  13. Intensive Therapy Study: Trough concentration (Ctrough) of ziftomenib

    Timeframe: During treatment for up to 36 months after last patient inclusion

    To characterize the Ctrough of ziftomenib

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

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.

Sources for eligibility
clinicaltrials.gov

  • Banner MD Anderson Cancer CenterGilbert, United StatesRecruiting
  • University of California, FresnoClovis, United StatesRecruiting
  • University of California, San DiegoLa Jolla, United StatesRecruiting
  • Cedars-Sinai Medical CenterLos Angeles, United StatesRecruiting
  • University of California, Los AngelesLos Angeles, United StatesRecruiting
  • University of California, IrvineOrange, United StatesRecruiting
  • University of ColoradoAurora, United StatesRecruiting
  • Colorado Blood Cancer InstituteDenver, United StatesRecruiting
  • Hartford HealthCare Cancer InstituteHartford, United StatesRecruiting
  • Yale University School of MedicineNew Haven, United StatesRecruiting
  • University of MiamiMiami, United StatesRecruiting
  • Moffitt Cancer Center & Research InstituteTampa, United StatesRecruiting
  • University of IowaIowa City, United StatesRecruiting
  • University of KentuckyLexington, United StatesRecruiting
  • University of MassachusettsWorcester, United StatesRecruiting
  • University of MichiganAnn Arbor, United StatesRecruiting
  • Wayne State University School of MedicineDetroit, United StatesRecruiting
  • University of MinnesotaMinneapolis, United StatesRecruiting
  • Rutgers Biomedical and Health SciencesNew Brunswick, United StatesRecruiting
  • University of New MexicoAlbuquerque, United StatesRecruiting
  • State University of New York at BuffaloBuffalo, United StatesRecruiting
  • Icahn School of Medicine at Mount SinaiNew York, United StatesRecruiting
  • Columbia UniversityNew York, United StatesRecruiting
  • Weill Cornell Medical CenterNew York, United StatesRecruiting
  • University of North Carolina, Chapel HillChapel Hill, United StatesRecruiting

And 90 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2025
  • 2025-521314-25-00
Sources for references
clinicaltrials.gov

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