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: 16 countries
• Sites: 106

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 (106)

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, Los Angeles

Los Angeles, California, 90095, 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 Iowa

Iowa City, Iowa, 52246, United States

RECRUITING

University of Kentucky

Lexington, Kentucky, 40536, United States

RECRUITING

University of Massachusetts

Worcester, Massachusetts, 01605, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, 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

State University of New York at Buffalo

Buffalo, New York, 14263, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10003, United States

RECRUITING

Columbia University

New York, New York, 10032, 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 Vermont Medical Center

Burlington, Vermont, 05401, 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

University of Wisconsin

Madison, Wisconsin, 53792, United States

RECRUITING

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Calvary Mater Newcastle

Waratah, New South Wales, 02298, Australia

RECRUITING

Box Hill Hospital

Heidelberg, Victoria, 3128, Australia

RECRUITING

Universitair Ziekenhuis Brussel

Jette, Brussels Capital, 1090, Belgium

RECRUITING

Centre Hospitalier Régional Verviers East Belgium

Verviers, Walloonia, 4800, Belgium

RECRUITING

Algemeen Ziekenhuis Sint-Jan Brugge

Bruges, West-Vlaanderen, 8800, Belgium

RECRUITING

Algemeen Ziekenhuis Delta VZW

Roeselare, West-Vlaanderen, 8800, Belgium

RECRUITING

Royal Victoria Hospital

Montreal, Quebec, H4A3J1, Canada

RECRUITING

Fakultni Nemocnice Ostrava

Ostrava-Poruba, Moravian-Silesian, 70852, Czechia

RECRUITING

Fakultní Nemocnice Královské Vinohrady

Prague, Prague, 10034, Czechia

RECRUITING

Centre Hospitalier Universitaire Estaing - Clermont-Ferrand

Clermont-Ferrand, Auvergne-Rhône-Alpes, 63003, France

RECRUITING

Hôpital Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France

RECRUITING

Centre Hospitalier Universitaire de Saint Etienne

Saint-Priest-en-Jarez, Auvergne-Rhône-Alpes, 42270, France

RECRUITING

Groupe Hospitalier de la Region de Mulhouse et Sud Alsace Hôpital Emile Muller

Mulhouse, Grand Est, 68100, France

RECRUITING

Centre Hospitalier Régional et Universitaire de Nancy Hôpitaux de Brabois

Vandœuvre-lès-Nancy, Grand Est, 54510, France

RECRUITING

Centre Hospitalier Universitaire de Nantes

Nantes, Loire-Atlantique, 44000, France

RECRUITING

Centre Hospitalier Universitaire de Bordeaux

Pessac, New Aquitaine, 33604, France

RECRUITING

Centre Henri Becquerel

Rouen, Normandy, 76038, France

RECRUITING

Centre Hospitalier de Béziers

Béziers, Occitanie, 35400, France

RECRUITING

Centre Hospitalier Universitaire de Marseille - Hôpital de la Conception

Marseille, Provence-Alpes-Côte d'Azur Region, 13385, France

RECRUITING

Hôpital Universitaire Henri Mondor

Créteil, Val-de-Marne, 94010, France

RECRUITING

Institut Gustave Roussy

Villejuif, Val-De-Marne, 94805, France

RECRUITING

Hôpital Avicenne

Bobigny, Île-de-France Region, 93009, France

RECRUITING

Centre Hospitalier de Versailles

Le Chesnay, Île-de-France Region, 78150, France

RECRUITING

Hôpital Saint Louis

Paris, Île-de-France Region, 75010, France

RECRUITING

Hôpital Pitié-Salpêtrière

Paris, Île-de-France Region, 75013, France

RECRUITING

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

RECRUITING

Laiko General Hospital of Athens

Athens, Attica, 11527, Greece

RECRUITING

Attikon University General Hospital of Athens

Chaïdári, Attica, 12462, Greece

RECRUITING

General Hospital of Thessaloniki G. Papanikolaou

Exochi, Central Macedonia, 57010, Greece

RECRUITING

University General Hospital of Alexandroupoli

Alexandroupoli, East Macedonia and Thrace, 68100, Greece

RECRUITING

University General Hospital of Ioannina

Ioannina, Epirus, 45500, Greece

RECRUITING

L'IRCCS Azienda Ospedaliero - Universitaria di Bologna

Bologna, Emilia-Romagna, 40138, Italy

RECRUITING

Hospital Santa Maria delle Croci

Ravenna, Emilia-Romagna, 48121, Italy

RECRUITING

ASUGI Ospedale Maggiore di Trieste

Trieste, Friuli Venezia Giulia, 76038, Italy

RECRUITING

Azienda Sanitaria Territoriale di Ascoli Piceno

Ascoli Piceno, The Marches, 63100, Italy

RECRUITING

Azienda Ospedaliero-Universitaria

Perugia, Umbria, 42270, Italy

RECRUITING

Baguio General Hospital and Medical Center

Baguio City, Benguet, 02600, Philippines

RECRUITING

University of Santo Tomas

Manila, National Capital Region, 1015, Philippines

RECRUITING

The Medical City

Pasig, National Capital Region, 1605, Philippines

RECRUITING

Szpital Wojewodzki w Opolu

Opole, Opole Voivodeship, 45-061, Poland

RECRUITING

Hospital de Braga, Centro Clínico Académico de Braga

Braga, 1099-023, Portugal

RECRUITING

Chungnam National University Daejeon Hospital

Daejeon, Daejeon Gwang'Yeogsi, 35015, South Korea

RECRUITING

Daegu Catholic University Hospital

Daegu, Gyeongsangbuk-do, 735-718, South Korea

RECRUITING

Pusan National University Hospital

Busan-si, Gyeongsangnam-do, 49241, South Korea

RECRUITING

Dong-A University Hospital

Pusan, Gyeongsangnam-do, 49201, South Korea

RECRUITING

Ulsan University Hospital

Ulsan, Gyeongsangnam-do, 44033, South Korea

RECRUITING

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 58128, South Korea

RECRUITING

Anam Hospital Korea University

Seoul, Seoul-T'Ukpyolsi, 02841, South Korea

RECRUITING

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, Seoul-T'Ukpyolsi, 137-040, South Korea

RECRUITING

Samsung Medical Center

Seoul, Seoul-T'Ukpyolsi, 35015, South Korea

RECRUITING

University Hospital Virgen Del Rocio S.L.

Seville, Andalusia, 41013, Spain

RECRUITING

Hospital Clinico Universitario Lozano Blesa

Zaragoza, Aragon, 50009, Spain

RECRUITING

Hospital Universitario De Burgos

Burgos, Castille and León, 09006, Spain

RECRUITING

Hospital General Universitario de Albacete

Albacete, Castille-La Mancha, 02006, Spain

RECRUITING

Hospital Universitario Infanta Leonor

Madrid, Madrid, 28031, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, València, 46010, Spain

RECRUITING

Hospital Universitario Y Politecnico La Fe

Valencia, València, 46026, Spain

RECRUITING

Chang Bing Show Chwan Memorial Hospital

Lugang, Central Taiwan, 505, Taiwan

RECRUITING

Taichung Veterans General Hospital

Taichung, Central Taiwan, 407, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, Northern Taiwan, 10002, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, Northern Taiwan, 613, Taiwan

RECRUITING

St. Bartholomew's Hospital

London, England, EC1A 7BE, United Kingdom

NOT YET RECRUITING

St. George's, University of London

London, England, SW17 0QT, United Kingdom

NOT YET 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: July 27, 2026

Record last verified: 2026-06

Locations

IT (5); BE (4); GB (2); ES (8); PL (1); CA (1); PT (1); DE (1); US (42); FR (16); AU (2); GR (5); PH (3); CZ (2); TW (4); KR (9)