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NCT05735184PHASE1Recruiting

A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, 7+3, or 7+3+Quizartinib in Patients With AML

Kura Oncology, Inc.

Start Date

7/18/2023

Completion Date

4/1/2030

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Ziftomenib

DRUG

Venetoclax

DRUG

Azacitidine

DRUG

Daunorubicin

DRUG

Cytarabine

DRUG

Quizartinib

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Conditions

Acute Myeloid LeukemiaMixed Lineage Leukemia Gene MutationRefractory AMLAML With Mutated NPM1Acute Myeloid Leukemia RecurrentAcute Myeloid Leukemia, in RelapseNPM1 MutationKMT2ArMyeloid SarcomaNucleophosmin 1-mutated Acute Myeloid Leukemia

Locations

Mayo Clinic - Phoenix

Phoenix, Arizona 85054

United States

Moores UC San Diego Cancer Center

La Jolla, California 92093

United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

UCLA - Bowyer Oncology Center

Los Angeles, California 90095

United States

UC Irvine Health Chao Family Comprehensive Cancer Center

Orange, California 92868

United States

University of Colorado

Aurora, Colorado 80045

United States

Colorado Blood Cancer Institute

Denver, Colorado 80218

United States

Yale Cancer Center and Smilow Cancer Hospital

New Haven, Connecticut 06510

United States

Mayo Clinic Jacksonville

Jacksonville, Florida 32224

United States

Emory Healthcare - The Emory Clinic

Atlanta, Georgia 30308

United States

Georgia Cancer Center at Augusta University

Augusta, Georgia 30912

United States

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois 60611

United States

Loyola University Medical Center

Maywood, Illinois 60153

United States

University of Iowa Hospitals & Clinics

Iowa City, Iowa 52242

United States

The University of Kansas Medical Center Research Institute

Fairway, Kansas 66205

United States

University of Kentucky Markey Cancer Center

Louisville, Kentucky 40202

United States

Norton Cancer Institute - St. Matthews

Louisville, Kentucky 40207

United States

Ochsner MD Anderson Cancer Center

Jefferson, Louisiana 70121

United States

Johns Hopkins School of Medicine

Baltimore, Maryland 21205

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

UMass Chan Medical School

Worcester, Massachusetts 01655

United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan 48109

United States

Karmanos Cancer Institute

Detroit, Michigan 48201

United States

University of Minnesota

Minneapolis, Minnesota 55455

United States

Mayo Clinic - Rochester

Rochester, Minnesota 55905

United States

Hackensack University Medical Center

Hackensack, New Jersey 07601

United States

Rutgers Cancer Institute

New Brunswick, New Jersey 08903

United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York 14203

United States

New York - Presbyterian / Weill Cornell Medicine

New York, New York 10021

United States

Mount Sinai - Ruttenberg Treatment Center

New York, New York 10029

United States

Columbia University Medical Center

New York, New York 10032

United States

Stony Brook University Hospital

Stony Brook, New York 11794

United States

Duke Blood Cancer Center

Durham, North Carolina 27705

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44106

United States

Cleveland Clinic Taussig Cancer Institute

Cleveland, Ohio 44195

United States

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio 43210

United States

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma 73104

United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

TriStar Bone Marrow Transplant

Nashville, Tennessee 37203

United States

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

Austin, Texas 78704

United States

UT Southwestern - Simmons Cancer Center

Dallas, Texas 75235

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin 53792

United States

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin 53226

United States