Phase 1 Study to Determine the Safety and Tolerability of Ziftomenib Combinations for the Treatment of KMT2A-rearranged or NPM1-mutant Relapsed/Refractory Acute Myeloid Leukemia
Summary
The safety, tolerability, and antileukemic response of ziftomenib in combination with standard of care treatments for patients with relapsed/refractory acute myeloid leukemia will be examined with the following agents: FLAG-IDA, low-dose cytarabine, and gilteritinib.
Arms & interventions
- DrugZiftomenib
Oral administration
- DrugFludarabine
Intravenous infusion
- DrugIdarubicin
Intravenous infusion
- DrugCytarabine
Intravenous Infusion
- DrugGilteritinib
Oral administration
- BiologicalGranulocyte colony-stimulating factor
Subcutaneous injection
Outcome measures
Primary
Rate of dose limiting toxicities (DLTs) per dose level
Assessed by the NCI-CTCAE v5.0
Time frame: During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle)
Descriptive statistics of adverse events
Assessed by the NCI-CTCAE v5.0
Time frame: First dose of ziftomenib up to and including 28 days after last dose of ziftomenib, or if the patient is lost to follow-up, whichever comes first
Secondary
Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2
Time frame: Up to 12 months following discontinuation of treatment
Complete remission (CR) / Complete remission with partial hematologic recovery (CRh) rate for cohort A-3
Time frame: Up to 12 months following discontinuation of treatment
Composite complete remission (CRc) rate
Time frame: Up to 12 months following discontinuation of treatment
Morphologic leukemia-free state (MLFS) rate
Time frame: Up to 12 months following discontinuation of treatment
OS
Time frame: Up to 12 months following discontinuation of treatment
6-month OS
Time frame: Up to 6 months following discontinuation of treatment
Median EFS
Time frame: Up to 12 months following discontinuation of treatment
6-month EFS
Time frame: Up to 6 months following discontinuation of treatment
DOR
Time frame: Up to 12 months following discontinuation of treatment
MRD assessment
Time frame: Up to 12 months following discontinuation of treatment
HSCT
Time frame: Up to 12 months following discontinuation of treatment
Transfusion independence
Time frame: Up to 12 months following discontinuation of treatment
Ziftomenib Cmax
Time frame: Cycle 1 (Each cycle is 28 days)
Ziftomenib Tmax
Time frame: Cycle 1 (Each cycle is 28 days)
Ziftomenib AUC(0-last)
Time frame: Cycle 1 (Each cycle is 28 days)
Ziftomenib AUC(tau)
Time frame: Cycle 1 (Each cycle is 28 days)
Gilteritinib Cmax
Time frame: Cycle 1 (Each cycle is 28 days)
Gilteritinib Tmax
Time frame: Cycle 1 (Each cycle is 28 days)
Gilteritinib AUC(0-last)
Time frame: Cycle 1 (Each cycle is 28 days)
Gilteritinib AUC(tau)
Time frame: Cycle 1 (Each cycle is 28 days)
Eligibility criteria
Study locations (38)
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90089
UCLA Health - Bowyer Oncology Center
Los Angeles, California, 90095
UC Irvine Health Chao Family Comprehensive Cancer Center
Orange, California, 92868
University of California San Francisco
San Francisco, California, 94115
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Smilow Cancer Hospital at Yale New Haven
New Haven, Connecticut, 06511
Emory Healthcare - The Emory Clinic
Atlanta, Georgia, 30322
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
Simmons Cancer Institute
Springfield, Illinois, 62702
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
The University of Kansas Cancer Center
Kansas City, Kansas, 66160
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Karmanos Cancer Institute
Detroit, Michigan, 48201
Henry Ford Cancer Institute
Detroit, Michigan, 48202
Washington University School of Medicine
St Louis, Missouri, 63110
University of Nebraska Medical Center
Omaha, Nebraska, 68198
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
Northwell Health, LLC PRIME
Lake Success, New York, 11042
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Weill Cornell Medical College-NY Presbyterian Hospital
New York, New York, 10065
Wilmot Cancer Institute, University of Rochester
Rochester, New York, 14642
Stony Brook Cancer Center
Stony Brook, New York, 11794
Atrium Health Levine Cancer Center
Charlotte, North Carolina, 60201
UH Seidman Cancer Center
Cleveland, Ohio, 44106
OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Lehigh Valley Topper Cancer Institute
Allentown, Pennsylvania, 18103
Prisma Health
Greenville, South Carolina, 29615
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
MD Anderson Cancer Center
Houston, Texas, 77030
University of Vermont
Burlington, Vermont, 05401
University of Virginia Comprehensive Cancer Center
Charlottesville, Virginia, 22903
University of Washington
Seattle, Washington, 98109
Froedtert & Medical College Clinics
Milwaukee, Wisconsin, 53226