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
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
Study locations (44)
Mayo Clinic - Phoenix
Phoenix, Arizona, 85054
Moores UC San Diego Cancer Center
La Jolla, California, 92093
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
UCLA - Bowyer Oncology Center
Los Angeles, California, 90095
UC Irvine Health Chao Family Comprehensive Cancer Center
Orange, California, 92868
University of Colorado
Aurora, Colorado, 80045
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Yale Cancer Center and Smilow Cancer Hospital
New Haven, Connecticut, 06510
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Emory Healthcare - The Emory Clinic
Atlanta, Georgia, 30308
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, 60611
Loyola University Medical Center
Maywood, Illinois, 60153
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
The University of Kansas Medical Center Research Institute
Fairway, Kansas, 66205
University of Kentucky Markey Cancer Center
Louisville, Kentucky, 40202
Norton Cancer Institute - St. Matthews
Louisville, Kentucky, 40207
Ochsner MD Anderson Cancer Center
Jefferson, Louisiana, 70121
Johns Hopkins School of Medicine
Baltimore, Maryland, 21205
Massachusetts General Hospital
Boston, Massachusetts, 02114
UMass Chan Medical School
Worcester, Massachusetts, 01655
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Karmanos Cancer Institute
Detroit, Michigan, 48201
University of Minnesota
Minneapolis, Minnesota, 55455
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Rutgers Cancer Institute
New Brunswick, New Jersey, 08903
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14203
New York - Presbyterian / Weill Cornell Medicine
New York, New York, 10021
Mount Sinai - Ruttenberg Treatment Center
New York, New York, 10029
Columbia University Medical Center
New York, New York, 10032
Stony Brook University Hospital
Stony Brook, New York, 11794
Duke Blood Cancer Center
Durham, North Carolina, 27705
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio, 44195
The James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
TriStar Bone Marrow Transplant
Nashville, Tennessee, 37203
Sarah Cannon Research Institute - St. David's South Austin Medical Center / Texas Oncology South Austin
Austin, Texas, 78704
UT Southwestern - Simmons Cancer Center
Dallas, Texas, 75235
MD Anderson Cancer Center
Houston, Texas, 77030
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, 53226
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)