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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05735184
• Other study ID #: KO-MEN-007
• Status: Recruiting
• Phase: Phase 1
• Start date: July 18, 2023
• Est. completion date: May 2027

Study information

• Verified date: April 2024
• Source: Kura Oncology, Inc.
• Contact: Clinical Operations
• Phone: 858 500 8800
• Email: KO-MEN-007[@]kuraoncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 212
• Est. completion date: May 2027
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Disease
• Acute Myeloid Leukemia
• Acute Myeloid Leukemia Recurrent
• Acute Myeloid Leukemia, in Relapse
• Leukemia
• Leukemia, Biphenotypic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Mixed Lineage Acute Leukemia
• Mixed Phenotype Acute Leukemia
• Myeloid Sarcoma
• Refractory AML
• Sarcoma, Myeloid

Intervention

Drug:
• Ziftomenib
Oral Administration
• Venetoclax
Oral Administration
• Azacitidine
Subcutaneous or Intravenous Administration
• Daunorubicin
Intravenous Administration
• Cytarabine
Intravenous Administration

Locations

Country	Name	City	State
United States	UC Health Blood Disorders and Cell Therapies Center - Anschutz Medical Campus	Aurora	Colorado
United States	Sarah Cannon Research Institute - St. David's South Austin Medical Center / Texas Oncology South Austin	Austin	Texas
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Robert H. Lurie Comprehensive Cancer Center of Northwestern University	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	UT Southwestern - Simmons Cancer Center	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Duke Blood Cancer Center	Durham	North Carolina
United States	The University of Kansas Cancer Center	Fairway	Kansas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Ochsner MD Anderson Cancer Center	Jefferson	Louisiana
United States	UCLA - Bowyer Oncology Center	Los Angeles	California
United States	USC University of Southern California / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Norton Cancer Institute - St. Matthews	Louisville	Kentucky
United States	UW Health - Carbone Cancer Center	Madison	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	TriStar Bone Marrow Transplant	Nashville	Tennessee
United States	Rutgers Cancer Institute	New Brunswick	New Jersey
United States	Yale Cancer Center and Smilow Cancer Hospital	New Haven	Connecticut
United States	Mount Sinai - Ruttenberg Treatment Center	New York	New York
United States	New York - Presbyterian / Weill Cornell Medicine	New York	New York
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	UCI Health Chao Family Comprehensive Cancer Center	Orange	California
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Stony Brook Cancer Center	Stony Brook	New York

Sponsors (1)

Lead Sponsor	Collaborator
Kura Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of dose limiting toxicities (DLTs) per dose level	Assessed by the NCI-CTCAE v5.0	During the first 28 days of ziftomenib in combination with SOC backbone treatment (1 cycle)
Primary	Descriptive statistics of adverse events	Assessed by the NCI-CTCAE v5.0	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
Primary	Complete remission (CR) rate	Assessed by the ELN 2022 criteria	Up to 1 year following end of treatment with ziftomenib
Secondary	Composite Complete Remission (CRc) or MLFS rate	Assessed by the ELN 2022 criteria	Up to 1 year following end of treatment with ziftomenib
Secondary	Measurable residual disease (MRD)	Assessed by multiparameter flow cytometry (MFC) and molecular analysis	Up to 1 year following end of treatment with ziftomenib
Secondary	Median OS	To assess overall survival of ziftomenib	Up to 1 year following end of treatment with ziftomenib
Secondary	Proportion of patients alive	To assess proportion of patients alive at 1 year following treatment with ziftomenib	1 year following end of treatment with ziftomenib
Secondary	Median EFS	To assess median event free survival	Up to 1 year following end of treatment with ziftomenib
Secondary	EFS	To assess event free survival	1 year following end of treatment with ziftomenib
Secondary	Median DOR	To assess median duration of remission	Up to 1 year following end of treatment with ziftomenib
Secondary	Proportion of patients who undergo HSCT	To assess proportion of patients who undergo hematopoietic stem cell transplant	Up to 1 year following end of treatment with ziftomenib
Secondary	TI	To assess rate of transfusion independence	Up to 1 year following end of treatment with ziftomenib
Secondary	Cmax	Maximum plasma concentration (Cmax) of ziftomenib and metabolites	Cycle 1. Each cycle is 28 days.
Secondary	Tmax	Time to maximum plasma concentration (Tmax) of ziftomenib and metabolites	Cycle 1. Each cycle is 28 days.
Secondary	AUC0-last	Area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing (AUC0-last) of ziftomenib and metabolites	Cycle 1. Each cycle is 28 days.
Secondary	AUCtau	Area under the concentration-time curve over a dosing interval (AUCtau) of ziftomenib	Cycle 1. Each cycle is 28 days.
Secondary	Accumulation ratio of ziftomenib and metabolites	To assess accumulation ratio of ziftomenib and metabolites	Cycle 1. Each cycle is 28 days.
Secondary	Cmax of venetoclax	Maximum plasma concentration (Cmax) of venetoclax	Cycle 1. Each cycle is 28 days.
Secondary	Tmax of venetoclax	Time to maximum plasma concentration (Tmax) of venetoclax	Cycle 1. Each cycle is 28 days.
Secondary	AUC0-last of venetoclax	Area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing (AUC0-last) of venetoclax	Cycle 1. Each cycle is 28 days.
Secondary	AUCtau of venetoclax	Area under the concentration-time curve over a dosing interval (AUCtau) of venetoclax	Cycle 1. Each cycle is 28 days.