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
Azacitidine: Subcutaneous or Intravenous Administration
Daunorubicin: Intravenous Administration
Cytarabine: Intravenous Administration
Quizartinib: Oral Administration
Study 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
Sex
ALL
Min age
18 Years
Max age
—
Healthy 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
Primary outcome measure(s)
Rate of dose limiting toxicities (DLTs) per dose level (Part 1a only) — During the first 28 days of ziftomenib in combination with SOC backbone treatment (1 cycle) Assessed by the NCI-CTCAE v5.0
Descriptive statistics of adverse events — From Cycle 1 Day 1 up to and including 28 days following the end of 36 months of treatment Assessed by the NCI-CTCAE v5.0
Complete remission (CR) rate — Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first Assessed by the ELN 2022 criteria
Trial sites (44)
Facility
City
Region
Status
Mayo Clinic - Phoenix
Phoenix
Arizona
Recruiting
Moores UC San Diego Cancer Center
La Jolla
California
Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles
California
Recruiting
UCLA - Bowyer Oncology Center
Los Angeles
California
Recruiting
UC Irvine Health Chao Family Comprehensive Cancer Center
Orange
California
Recruiting
University of Colorado
Aurora
Colorado
Recruiting
Colorado Blood Cancer Institute
Denver
Colorado
Recruiting
Yale Cancer Center and Smilow Cancer Hospital
New Haven
Connecticut
Recruiting
Mayo Clinic Jacksonville
Jacksonville
Florida
Recruiting
Emory Healthcare - The Emory Clinic
Atlanta
Georgia
Recruiting
Georgia Cancer Center at Augusta University
Augusta
Georgia
Recruiting
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago
Illinois
Recruiting
Loyola University Medical Center
Maywood
Illinois
Recruiting
University of Iowa Hospitals & Clinics
Iowa City
Iowa
Recruiting
The University of Kansas Medical Center Research Institute
Fairway
Kansas
Recruiting
University of Kentucky Markey Cancer Center
Louisville
Kentucky
Recruiting
Norton Cancer Institute - St. Matthews
Louisville
Kentucky
Recruiting
Ochsner MD Anderson Cancer Center
Jefferson
Louisiana
Recruiting
Johns Hopkins School of Medicine
Baltimore
Maryland
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
UMass Chan Medical School
Worcester
Massachusetts
Recruiting
University of Michigan Comprehensive Cancer Center
Ann Arbor
Michigan
Recruiting
Karmanos Cancer Institute
Detroit
Michigan
Recruiting
University of Minnesota
Minneapolis
Minnesota
Recruiting
Mayo Clinic - Rochester
Rochester
Minnesota
Recruiting
Hackensack University Medical Center
Hackensack
New Jersey
Recruiting
Rutgers Cancer Institute
New Brunswick
New Jersey
Recruiting
Roswell Park Comprehensive Cancer Center
Buffalo
New York
Recruiting
New York - Presbyterian / Weill Cornell Medicine
New York
New York
Recruiting
Mount Sinai - Ruttenberg Treatment Center
New York
New York
Recruiting
Columbia University Medical Center
New York
New York
Recruiting
Stony Brook University Hospital
Stony Brook
New York
Recruiting
Duke Blood Cancer Center
Durham
North Carolina
Recruiting
University Hospitals Cleveland Medical Center
Cleveland
Ohio
Recruiting
Cleveland Clinic Taussig Cancer Institute
Cleveland
Ohio
Recruiting
The James Cancer Hospital and Solove Research Institute
Columbus
Ohio
Recruiting
OU Health Stephenson Cancer Center
Oklahoma City
Oklahoma
Recruiting
Hospital of the University of Pennsylvania
Philadelphia
Pennsylvania
Recruiting
TriStar Bone Marrow Transplant
Nashville
Tennessee
Recruiting
Sarah Cannon Research Institute - St. David's South Austin Medical Center / Texas Oncology South Austin
Austin
Texas
Recruiting
+ 4 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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