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RecruitingInterventionalPhase 1

Phase 1 Study of Venetoclax/Azacitidine or Venetoclax in Combination With Ziftomenib or Standard Induction Cytarabine/Daunorubicin (7+3) Chemotherapy in Combination With Ziftomenib for the Treatment of Patients With Acute Myeloid Leukemia

NCT ID: NCT05735184Sponsor: Kura Oncology, Inc.Last updated: 2026-03-13

Summary

Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with certain genetic alterations. This protocol has 3 separate arms that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) drug treatments in patients who have AML with certain genetic mutations. Both newly diagnosed and relapsed refractory patients with AML will be assigned to different cohorts based on specific study criteria and physician discretion. The purpose of this study is to assess the safety, tolerability, and early signs of efficacy of ziftomenib in combination with SOC drugs to treat AML.

Arms & interventions

  • DrugZiftomenib

    Oral Administration

  • DrugVenetoclax

    Oral Administration

  • DrugAzacitidine

    Subcutaneous or Intravenous Administration

  • DrugDaunorubicin

    Intravenous Administration

  • DrugCytarabine

    Intravenous Administration

  • DrugQuizartinib

    Oral Administration

Outcome measures

Primary

  • Rate of dose limiting toxicities (DLTs) per dose level (Part 1a only)

    Assessed by the NCI-CTCAE v5.0

    Time frame: During the first 28 days of ziftomenib in combination with SOC backbone treatment (1 cycle)

  • Descriptive statistics of adverse events

    Assessed by the NCI-CTCAE v5.0

    Time frame: From Cycle 1 Day 1 up to and including 28 days following the end of 36 months of treatment

  • Complete remission (CR) rate

    Assessed by the ELN 2022 criteria

    Time frame: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first

Secondary

  • Composite Complete Remission (CRc)

    Time frame: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first

  • Morphologic leukemia-free state (MLFS) rate

    Time frame: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever comes first

  • Measurable residual disease (MRD)

    Time frame: Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first

  • Median OS

    Time frame: From Cycle 1 Day 1 to date of death from any cause, assessed up to 36 months of treatment

  • Proportion of patients alive

    Time frame: From Cycle 1 Day 1 until death from any cause, assessed up to 1 year following start of treatment

  • Median EFS

    Time frame: From Cycle 1 Day 1 to treatment failure, hematologic relapse following CR, or death from any cause, whichever comes first, assessed up to 36 months of treatment

  • EFS

    Time frame: From Cycle 1 Day 1 to treatment failure, hematologic relapse following CR, or death from any cause, whichever comes first, assessed up to 1 year following start of treatment

  • Median DOR

    Time frame: From time of first remission to relapse or death, whichever occurs first, assessed up to 36 months from start of treatment

  • Proportion of patients who undergo HSCT

    Time frame: From Cycle 1 Day 1 until date of HSCT, assessed up to 36 months of treatment

  • TI

    Time frame: From 28 days prior to Cycle 1 Day 1 up to and including 28 days following the end of 36 months of treatment

  • Cmax

    Time frame: Cycle 1; each cycle is 28 days

  • Tmax

    Time frame: Cycle 1; each cycle is 28 days

  • AUC0-last

    Time frame: Cycle 1; each cycle is 28 days

  • AUCtau

    Time frame: Cycle 1; each cycle is 28 days

  • Accumulation ratio of ziftomenib and metabolites

    Time frame: Cycle 1; each cycle is 28 days

  • Cmax of venetoclax

    Time frame: Cycle 1; each cycle is 28 days

  • Tmax of venetoclax

    Time frame: Cycle 1; each cycle is 28 days

  • AUC0-last of venetoclax

    Time frame: Cycle 1; each cycle is 28 days

  • AUCtau of venetoclax

    Time frame: Cycle 1; each cycle is 28 days

  • Cmax of quizartinib

    Time frame: Cycle 1; each cycle is 28 days

  • Tmax of quizartinib

    Time frame: Cycle 1; each cycle is 28 days

  • AUC0-last of quizartinib

    Time frame: Cycle 1; each cycle is 28 days

  • AUCtau of quizartinib

    Time frame: Cycle 1; each cycle is 28 days

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Key Inclusion Criteria: * Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML * Those intending treatment with intensive chemotherapy in Arm C should be NPM1-m and FLT3-ITD+ with an allelic ratio ≥0.05 and eligible for FLT3-targeted treatment * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Adequate liver, renal, and cardiac function according to protocol defined criteria * A female of childbearing potential must agree to use adequate contraception as well as a double barrier method from the time of screening through 180 days following the last dose of study intervention. A male of childbearing potential must agree to use abstinence or use a double barrier method of contraception from the time of screening through 180 days following the last dose of study intervention * Female patients of childbearing potential who receive quizartinib in Arm C should use a highly effective method of contraception during quizartinib treatment and for 7 months after the last dose Key Exclusion Criteria: * Diagnosis of either acute promyelocytic leukemia or blast phase chronic myeloid leukemia * Known history of BCR-ABL alteration * Advanced malignant hepatic tumor * Administration of live attenuated vaccines within 14 days prior to, during, or after treatment until B-cell recovery * Active central nervous system (CNS) involvement by AML. * Clinical signs/symptoms of leukostasis or WBC \> 25,000 / microliter. Hydroxyurea and/or leukapheresis and/or up to 2 doses of cytarabine if used per institutional SOC for control of leukocytosis are permitted to meet this criterion * Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities except for alopecia * Known clinically active human immunodeficiency virus, active hepatitis B or active hepatitis C infection * For newly diagnosed cohorts: received prior chemotherapy for leukemia, except hydroxyurea and/or leukapheresis and/or up to 2 doses of cytarabine per institutional standards to control leukocytosis, or prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia * For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug * Uncontrolled intercurrent illness including, but not limited to, cardiac illness as defined in the protocol * Mean QT interval corrected for heart rate by Fredericia's formula (QTcF) * Arm A and Arm B: \>480 ms on triplicate ECGs * Arm C: \>450 ms on triplicate ECGs * Uncontrolled infection * Women who are pregnant or lactating * An active malignancy and currently receiving chemotherapy for that malignancy or disease that is uncontrolled/progressing * Patients who have active GVHD requiring \>0.5 mg/kg prednisone or any new or increase in immunosuppressants in the prior 2 weeks for GVHD treatment

Study locations (44)

Mayo Clinic - Phoenix

Phoenix, Arizona, 85054

Recruiting
Clinical Trials Referral Office · Contact

Moores UC San Diego Cancer Center

La Jolla, California, 92093

Recruiting
Krisma Montalvo · Contact

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033

Recruiting
Christine Duran · Contact

UCLA - Bowyer Oncology Center

Los Angeles, California, 90095

Recruiting
Bruck Habtemariam · Contact

UC Irvine Health Chao Family Comprehensive Cancer Center

Orange, California, 92868

Recruiting
Research Line · Contact

University of Colorado

Aurora, Colorado, 80045

Recruiting

Colorado Blood Cancer Institute

Denver, Colorado, 80218

Recruiting

Yale Cancer Center and Smilow Cancer Hospital

New Haven, Connecticut, 06510

Recruiting
Farah Fasihuddin · Contact

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224

Recruiting
Clinical Trials Referral Office · Contact

Emory Healthcare - The Emory Clinic

Atlanta, Georgia, 30308

Recruiting
Gigi Stoneback · Contact

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912

Recruiting
Amanda Spires · Contact

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611

Recruiting

Loyola University Medical Center

Maywood, Illinois, 60153

Recruiting

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242

Recruiting
Cena Jones · Contact

The University of Kansas Medical Center Research Institute

Fairway, Kansas, 66205

Recruiting
Thania Medrano · Contact

University of Kentucky Markey Cancer Center

Louisville, Kentucky, 40202

Recruiting
Ashley Walton-Robbins · Contact

Norton Cancer Institute - St. Matthews

Louisville, Kentucky, 40207

Recruiting

Ochsner MD Anderson Cancer Center

Jefferson, Louisiana, 70121

Recruiting
Amanda Woolery, RN · Contact

Johns Hopkins School of Medicine

Baltimore, Maryland, 21205

Recruiting
I. Gojo · Contact

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting
Christine Connelly · Contact

UMass Chan Medical School

Worcester, Massachusetts, 01655

Recruiting

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109

Recruiting
Cancer AnswerLine · Contact

Karmanos Cancer Institute

Detroit, Michigan, 48201

Recruiting
Carmen Rush · Contact

University of Minnesota

Minneapolis, Minnesota, 55455

Recruiting

Mayo Clinic - Rochester

Rochester, Minnesota, 55905

Recruiting
Clinical Trials Referral Office · Contact

Hackensack University Medical Center

Hackensack, New Jersey, 07601

Recruiting
Oncology Clinical Research Referral Office · Contact

Rutgers Cancer Institute

New Brunswick, New Jersey, 08903

Recruiting
Anita Trupiano · Contact

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203

Recruiting

New York - Presbyterian / Weill Cornell Medicine

New York, New York, 10021

Recruiting
Tania J Curcio · Contact

Mount Sinai - Ruttenberg Treatment Center

New York, New York, 10029

Recruiting
Tina Czaplinska · Contact

Columbia University Medical Center

New York, New York, 10032

Recruiting
Research Nurse Navigator · Contact

Stony Brook University Hospital

Stony Brook, New York, 11794

Recruiting

Duke Blood Cancer Center

Durham, North Carolina, 27705

Recruiting
Quinna Lawson · Contact

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106

Recruiting
Sarah Gollwitzer · Contact

Cleveland Clinic Taussig Cancer Institute

Cleveland, Ohio, 44195

Recruiting
Cancer Answer Line · Contact

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210

Recruiting
Hanna Cordes · Contact

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104

Recruiting
Cynthia Lowery · Contact

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104

Recruiting
Jessica Ritter · Contact
Camilla Ludlow · Contact

TriStar Bone Marrow Transplant

Nashville, Tennessee, 37203

Recruiting
Ask Sarah · Contact

Sarah Cannon Research Institute - St. David's South Austin Medical Center / Texas Oncology South Austin

Austin, Texas, 78704

Recruiting
Amy Hammack · Contact

UT Southwestern - Simmons Cancer Center

Dallas, Texas, 75235

Recruiting

MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Ramya Ganesh · Contact

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792

Recruiting
UW Cancer Connect · Contact

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226

Recruiting
Medical College of WI Cancer Center Clinical Trials Office · Contact

References

  • Wang ES, Erba HP, Zeidan AM, Roboz GJ, Altman JK, Advani AS, Lin TL, Strickland SA, Juckett MB, Pratz KW, Mangan JK, McMahon CM, Alsfeld LC, Balasubramanian SK, Guru Murthy GS, Rotta M, Palmisiano N, McCloskey J, Saliba AN, Khawandanah M, Madanat YF, Naqvi K, Qasrawi AH, Schiller GJ, Badar T, Gojo I, Yaghmour G, Osman D, Zhang H, Tian Y, Soifer HS, Riches M, Corum D, Leoni M, Fathi AT, Issa GC. Ziftomenib with venetoclax and azacitidine in relapsed/refractory NPM1-mutated acute myeloid leukemia. Blood. 2026 Jun 2:blood.2026034043. doi: 10.1182/blood.2026034043. Online ahead of print.(PubMed)