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

NCT07007312 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: KO-MEN-0172025-521314-25-00
• Study Type: interventional
• Target: 1,300
• Locations: 3 countries
• Sites: 39

Brief 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".

Conditions

Acute Myeloid Leukemia (AML)

Keywords

AML; Hematological malignancy; KMT2A; NPM1; Menin; Acute Leukemia; Leukemia; Acute Myeloid Leukemia; Newly diagnosed AML; Newly diagnosed KMT2A-r AML; Newly diagnosed NPM1m AML; Untreated AML; Untreated NPM1m AML; Untreated KMT2A-r AML; MLL

Outcome Measures

Primary Outcomes (4)

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

  OS

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

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

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

  Assessed up to 36 months after last patient inclusion

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

  EFS

  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

• 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

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

  Assessed up to 36 months after last patient inclusion

Secondary Outcomes (13)

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

  Up to 36 months after last patient inclusion

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

  Up to 36 months after last patient inclusion

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

  Up to 36 months after last patient inclusion

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

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

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

  During treatment for up to 36 months after last patient inclusion

Study Arms (5)

Nonintensive Therapy Study, Arm A

EXPERIMENTAL

Ziftomenib in combination with venetoclax+azacitidine

Drug: Ziftomenib; Drug: Venetoclax; Drug: Azacitidine (AZA)

Nonintensive Therapy Study, Arm B

PLACEBO COMPARATOR

Placebo in combination with venetoclax+azacitidine

Drug: Placebo; Drug: Venetoclax; Drug: Azacitidine (AZA)

Intensive Therapy Study, Arm A

EXPERIMENTAL

Ziftomenib+cytarabine+daunorubicin (induction), ziftomenib+cytarabine (consolidation), ziftomenib (maintenance)

Drug: Ziftomenib; Drug: Daunorubicin; Drug: Cytarabine (Ara-C)

Intensive Therapy Study, Arm B

EXPERIMENTAL

Ziftomenib+cytarabine+daunorubicin (induction), ziftomenib+cytarabine (consolidation), placebo (maintenance)

Drug: Ziftomenib; Drug: Placebo; Drug: Daunorubicin; Drug: Cytarabine (Ara-C)

Intensive Therapy Study, Arm C

PLACEBO COMPARATOR

Placebo+cytarabine+daunorubicin (induction), placebo+cytarabine (consolidation), placebo (maintenance)

Drug: Placebo; Drug: Daunorubicin; Drug: Cytarabine (Ara-C)

Interventions

Ziftomenib DRUG

Oral administration

Also known as: KO-539

Intensive Therapy Study, Arm A; Intensive Therapy Study, Arm B; Nonintensive Therapy Study, Arm A

Placebo DRUG

Oral administration

Intensive Therapy Study, Arm B; Intensive Therapy Study, Arm C; Nonintensive Therapy Study, Arm B

Venetoclax DRUG

Oral administration

Also known as: Venclexta, Venclyxto

Nonintensive Therapy Study, Arm A; Nonintensive Therapy Study, Arm B

Azacitidine (AZA) DRUG

Intravenous or subcutaneous administration

Also known as: Vidaza, Azadine

Nonintensive Therapy Study, Arm A; Nonintensive Therapy Study, Arm B

Daunorubicin DRUG

Intravenous administration

Also known as: Cerubidine, daunomycin

Intensive Therapy Study, Arm A; Intensive Therapy Study, Arm B; Intensive Therapy Study, Arm C

Cytarabine (Ara-C) DRUG

Intravenous administration

Also known as: cytosine arabinoside (ara-C), Cytosar-U, Tarabine PFS

Intensive Therapy Study, Arm A; Intensive Therapy Study, Arm B; Intensive Therapy Study, Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• Documented NPM1-m.
• 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):
• Documented NPM1-m or KMT2A-r (KMT2A-r patients with a partial tandem duplication are not eligible).
• 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.
• Ejection fraction of ≥50%.

You may not qualify if:

• 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:
• Basal cell skin cancer or localized squamous cell cancer of the skin
• Previous malignancy confined and locally resected (or treated with other modalities) with curative intent
• 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.

Sponsors & Collaborators

• Kura Oncology, Inc.: lead

Study Sites (39)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

RECRUITING

University of California, Fresno

Clovis, California, 93611, United States

RECRUITING

University of California, San Diego

La Jolla, California, 92093, United States

RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

University of California, Irvine

Orange, California, 92868, United States

RECRUITING

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

RECRUITING

Hartford HealthCare Cancer Institute

Hartford, Connecticut, 06106, United States

RECRUITING

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

RECRUITING

University of Kentucky

Lexington, Kentucky, 40536, United States

RECRUITING

Wayne State University School of Medicine

Detroit, Michigan, 48201, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

Rutgers Biomedical and Health Sciences

New Brunswick, New Jersey, 08903, United States

RECRUITING

University of New Mexico

Albuquerque, New Mexico, 87131, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10003, United States

RECRUITING

Weill Cornell Medical Center

New York, New York, 10065, United States

RECRUITING

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Willamette Valley Cancer Institute

Eugene, Oregon, 97401, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Baptist Clinical Research Institute

Memphis, Tennessee, 38120, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

TriStar Centennial Medical Center

Nashville, Tennessee, 37203, United States

RECRUITING

Texas Oncology-Austin Midtown

Austin, Texas, 78705, United States

RECRUITING

Texas Oncology-Presbyterian Cancer Center

Dallas, Texas, 75231, United States

RECRUITING

University of Texas

Houston, Texas, 77030, United States

RECRUITING

Texas Oncology - San Antonio Medical Center

San Antonio, Texas, 78240, United States

RECRUITING

University of Virginia School of Medicine

Charlottesville, Virginia, 22903, United States

RECRUITING

Virginia Cancer Specialists

Manassas, Virginia, 20110, United States

RECRUITING

WVU Medicine Wheeling Hospital

Wheeling, West Virginia, 26003, United States

RECRUITING

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Centre Hospitalier de Béziers

Béziers, 35400, France

RECRUITING

Centre Hospitalier Universitaire de Nantes

Nantes, 44000, France

RECRUITING

Dong-A University Hospital

Busan, 49201, South Korea

RECRUITING

Chungnam National University Daejeon Hospital

Daejeon, 35015, South Korea

RECRUITING

Chonnam National University Hwasun Hospital

Hwasun, 58128, South Korea

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Hematologic Neoplasms; Leukemia

Interventions

venetoclax; Azacitidine; Daunorubicin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Arabinonucleosides

Central Study Contacts

Kura Medical Information

CONTACT

844-KURAONC (844-587-2662); medinfo@kuraoncology.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 16, 2025
• First Posted: June 5, 2025
• Study Start: September 26, 2025
• Primary Completion (Estimated): November 1, 2031
• Study Completion (Estimated): November 1, 2031
• Last Updated: April 9, 2026

Record last verified: 2026-02

Locations

US (34); FR (2); KR (3)