Clinical trial NCT05735184: A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, or 7+3 in Patients With AML
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Mixed Lineage Acute Leukemia
Mixed Lineage Leukemia Gene Mutation
Mixed Phenotype Acute Leukemia
Refractory AML
AML With Mutated NPM1
Acute Myeloid Leukemia Recurrent
Acute Myeloid Leukemia, in Relapse
NPM1 Mutation
KMT2Ar
Myeloid Sarcoma
Lead sponsor: Kura Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-21
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This Phase 1 study will assess the safety, tolerability, and preliminary antileukemic activity of ziftomenib in combination with venetoclax and azacitidine (ven/aza), ven, and 7+3 for two different molecularly-defined arms, NPM1-m and KMT2A-r.


Eligibility criteria: Key Inclusion Criteria:

* Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML
* 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 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 adequate contraception from the time of screening through 90 days following the last dose of study intervention

Key Exclusion Criteria:

* Diagnosis of either acute promyelocytic leukemia or blast chronic myelomonocytic leukemia
* Known history of BCR-ABL alteration
* Advanced malignant hepatic tumor \[for patients receiving ven/aza combination\]
* 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 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 to control leukocytosis, prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia, or non-HMA therapy for prior myelodysplastic syndrome
* 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 corrected QT interval corrected for heart rate by Fredericia's formula (QTcF) \>480 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

Primary outcomes:
measure: Rate of dose limiting toxicities (DLTs) per dose level
timeFrame: During the first 28 days of ziftomenib in combination with SOC backbone treatment (1 cycle)
measure: Descriptive statistics of adverse events
timeFrame: 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
measure: Complete remission (CR) rate
timeFrame: Up to 1 year following end of treatment with ziftomenib
Secondary outcomes:
measure: Composite Complete Remission (CRc) or MLFS rate
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: Measurable residual disease (MRD)
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: Median OS
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: Proportion of patients alive
timeFrame: 1 year following end of treatment with ziftomenib
measure: Median EFS
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: EFS
timeFrame: 1 year following end of treatment with ziftomenib
measure: Median DOR
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: Proportion of patients who undergo HSCT
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: TI
timeFrame: Up to 1 year following end of treatment with ziftomenib
measure: Cmax
timeFrame: Cycle 1. Each cycle is 28 days.
measure: Tmax
timeFrame: Cycle 1. Each cycle is 28 days.
measure: AUC0-last
timeFrame: Cycle 1. Each cycle is 28 days.
measure: AUCtau
timeFrame: Cycle 1. Each cycle is 28 days.
measure: Accumulation ratio of ziftomenib and metabolites
timeFrame: Cycle 1. Each cycle is 28 days.
measure: Cmax of venetoclax
timeFrame: Cycle 1. Each cycle is 28 days.
measure: Tmax of venetoclax
timeFrame: Cycle 1. Each cycle is 28 days.
measure: AUC0-last of venetoclax
timeFrame: Cycle 1. Each cycle is 28 days.
measure: AUCtau of venetoclax
timeFrame: Cycle 1. Each cycle is 28 days.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - Phoenix
state: Arizona
city: La Jolla
country: United States
facility: Moores UC San Diego Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA - Bowyer Oncology Center
state: California
city: Orange
country: United States
facility: UC Irvine Health Chao Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: UC Health Blood Disorders and Cell Therapies Center - Anschutz Medical Campus
state: Colorado
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center and Smilow Cancer Hospital
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Emory Healthcare - The Emory Clinic
state: Georgia
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center of Northwestern University
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Fairway
country: United States
facility: The University of Kansas Medical Center Research Institute
state: Kansas
city: Louisville
country: United States
facility: University of Kentucky Markey Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute - St. Matthews
state: Kentucky
city: Jefferson
country: United States
facility: Ochsner MD Anderson Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: UMass Chan Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: St. Louis
country: United States
facility: Mayo Clinic - Rochester
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: New York - Presbyterian / Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Mount Sinai - Ruttenberg Treatment Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Durham
country: United States
facility: Duke Blood Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute
state: Ohio
city: Columbus
country: United States
facility: The James Cancer Hospital and Solove Research Institute
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: TriStar Bone Marrow Transplant
state: Tennessee
city: Austin
country: United States
facility: Sarah Cannon Research Institute - St. David's South Austin Medical Center / Texas Oncology South Austin
state: Texas
city: Dallas
country: United States
facility: UT Southwestern - Simmons Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
Study officials:
References: