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

NCT ID: NCT05735184

Last Updated: 2025-10-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-18

Study Completion Date

2030-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Acute Myeloid Leukemia Mixed Lineage Leukemia Gene Mutation Refractory AML AML With Mutated NPM1 Acute Myeloid Leukemia Recurrent Acute Myeloid Leukemia, in Relapse NPM1 Mutation KMT2Ar Myeloid Sarcoma Nucleophosmin 1-mutated Acute Myeloid Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1)

Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Venetoclax

Intervention Type DRUG

Oral Administration

Azacitidine

Intervention Type DRUG

Subcutaneous or Intravenous Administration

Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1)

Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Venetoclax

Intervention Type DRUG

Oral Administration

Azacitidine

Intervention Type DRUG

Subcutaneous or Intravenous Administration

Dose Escalation: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2)

Ziftomenib with 7+3 in newly diagnosed NPM1-m AML patients who are candidates for intensive chemotherapy and must be FLT3 wildtype or ITD ratio \<0.05

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Daunorubicin

Intervention Type DRUG

Intravenous Administration

Cytarabine

Intervention Type DRUG

Intravenous Administration

Dose Validation/Expansion: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2)

Ziftomenib with 7+3 in newly diagnosed NPM1-m AML patients who are candidates for intensive chemotherapy and must be FLT3 wildtype or ITD ratio \<0.05

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Daunorubicin

Intervention Type DRUG

Intravenous Administration

Cytarabine

Intervention Type DRUG

Intravenous Administration

Dose Validation/Expansion: Ziftomenib with Venetoclax in R/R NPM1-m (A-3)

Ziftomenib with Venetoclax in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Venetoclax

Intervention Type DRUG

Oral Administration

Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in 1L NPM1-m (A-4)

Ziftomenib with Venetoclax and Azacitidine in newly diagnosed NPM1-m AML patients

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Venetoclax

Intervention Type DRUG

Oral Administration

Azacitidine

Intervention Type DRUG

Subcutaneous or Intravenous Administration

Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1)

Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Venetoclax

Intervention Type DRUG

Oral Administration

Azacitidine

Intervention Type DRUG

Subcutaneous or Intravenous Administration

Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1)

Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Venetoclax

Intervention Type DRUG

Oral Administration

Azacitidine

Intervention Type DRUG

Subcutaneous or Intravenous Administration

Dose Escalation: Ziftomenib with 7+3 in 1L KMT2A-r (B-2)

Ziftomenib with 7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive chemotherapy

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Daunorubicin

Intervention Type DRUG

Intravenous Administration

Cytarabine

Intervention Type DRUG

Intravenous Administration

Dose Validation/Expansion: Ziftomenib with 7+3 in 1L KMT2A-r (B-2)

Ziftomenib with 7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive therapy

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Daunorubicin

Intervention Type DRUG

Intravenous Administration

Cytarabine

Intervention Type DRUG

Intravenous Administration

Dose Validation/Expansion: Ziftomenib with Venetoclax + Azacitidine in 1L KMT2A-r (B-3)

Ziftomenib with Venetoclax and Azacitidine in newly diagnosed KMT2A-r AML patients

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Venetoclax

Intervention Type DRUG

Oral Administration

Azacitidine

Intervention Type DRUG

Subcutaneous or Intravenous Administration

Dose Escalation: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1)

Ziftomenib with 7+3 and quizartinib in newly diagnosed NPM1-m and FLT3-ITD+ (with allelic ratio ≥0.05) AML patients who are candidates for IC and eligible to receive FLT3-targeted therapy

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Daunorubicin

Intervention Type DRUG

Intravenous Administration

Cytarabine

Intervention Type DRUG

Intravenous Administration

Quizartinib

Intervention Type DRUG

Oral Administration

Dose Validation/Expansion: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1)

Ziftomenib with 7+3 and quizartinib in newly diagnosed NPM1-m and FLT3-ITD+ (with allelic ratio ≥0.05) AML patients who are candidates for IC and eligible to receive FLT3-targeted therapy

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral Administration

Daunorubicin

Intervention Type DRUG

Intravenous Administration

Cytarabine

Intervention Type DRUG

Intravenous Administration

Quizartinib

Intervention Type DRUG

Oral Administration

Interventions

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Ziftomenib

Oral Administration

Intervention Type DRUG

Venetoclax

Oral Administration

Intervention Type DRUG

Azacitidine

Subcutaneous or Intravenous Administration

Intervention Type DRUG

Daunorubicin

Intravenous Administration

Intervention Type DRUG

Cytarabine

Intravenous Administration

Intervention Type DRUG

Quizartinib

Oral Administration

Intervention Type DRUG

Other Intervention Names

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KO-539 Venclexta Venclyxto Azadine Vidaza Cerubidine daunomycin cytosine arabinoside (ara-C) Cytosar-U Tarabine PFS Vanflyta

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kura Oncology, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Mayo Clinic - Phoenix

Phoenix, Arizona, United States

Site Status RECRUITING

Moores UC San Diego Cancer Center

La Jolla, California, United States

Site Status RECRUITING

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

UCLA - Bowyer Oncology Center

Los Angeles, California, United States

Site Status RECRUITING

UC Irvine Health Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status RECRUITING

University of Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status RECRUITING

Yale Cancer Center and Smilow Cancer Hospital

New Haven, Connecticut, United States

Site Status RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status RECRUITING

Emory Healthcare - The Emory Clinic

Atlanta, Georgia, United States

Site Status RECRUITING

Georgia Cancer Center at Augusta University

Augusta, Georgia, United States

Site Status RECRUITING

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

Loyola University Medical Center

Maywood, Illinois, United States

Site Status RECRUITING

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status RECRUITING

The University of Kansas Medical Center Research Institute

Fairway, Kansas, United States

Site Status RECRUITING

University of Kentucky Markey Cancer Center

Louisville, Kentucky, United States

Site Status RECRUITING

Norton Cancer Institute - St. Matthews

Louisville, Kentucky, United States

Site Status RECRUITING

Ochsner MD Anderson Cancer Center

Jefferson, Louisiana, United States

Site Status RECRUITING

Johns Hopkins School of Medicine

Baltimore, Maryland, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

UMass Chan Medical School

Worcester, Massachusetts, United States

Site Status RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status RECRUITING

Rutgers Cancer Institute

New Brunswick, New Jersey, United States

Site Status RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status RECRUITING

New York - Presbyterian / Weill Cornell Medicine

New York, New York, United States

Site Status RECRUITING

Mount Sinai - Ruttenberg Treatment Center

New York, New York, United States

Site Status RECRUITING

Columbia University Medical Center

New York, New York, United States

Site Status RECRUITING

Stony Brook University Hospital

Stony Brook, New York, United States

Site Status RECRUITING

Duke Blood Cancer Center

Durham, North Carolina, United States

Site Status RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status RECRUITING

Cleveland Clinic Taussig Cancer Institute

Cleveland, Ohio, United States

Site Status RECRUITING

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

Site Status RECRUITING

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

TriStar Bone Marrow Transplant

Nashville, Tennessee, United States

Site Status RECRUITING

Sarah Cannon Research Institute - St. David's South Austin Medical Center / Texas Oncology South Austin

Austin, Texas, United States

Site Status RECRUITING

UT Southwestern - Simmons Cancer Center

Dallas, Texas, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status RECRUITING

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Clinical Operations

Role: CONTACT

617-588-3755

Facility Contacts

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Clinical Trials Referral Office

Role: primary

855-776-0015

Krisma Montalvo

Role: primary

Christine Duran

Role: primary

323-865-0371

Bruck Habtemariam

Role: primary

310-794-0242

Research Line

Role: primary

877-827-8839

Patient Clinic

Role: primary

720-754-4800

Farah Fasihuddin

Role: primary

203-737-3472

Clinical Trials Referral Office

Role: primary

855-776-0015

Gigi Stoneback

Role: primary

Amanda Spires

Role: primary

Role: primary

312-695-9367

Cena Jones

Role: primary

Thania Medrano

Role: primary

913-945-7552

Ashley Walton-Robbins

Role: primary

Role: primary

502-899-3366

Amanda Woolery, RN

Role: primary

504-842-0275

I. Gojo

Role: primary

Christine Connelly

Role: primary

617-724-1124

Role: primary

508-856-3216

Cancer AnswerLine

Role: primary

800-865-1125

Carmen Rush

Role: primary

800-527-6266

Clinical Trials Referral Office

Role: primary

855-776-0015

Oncology Clinical Research Referral Office

Role: primary

551-996-1777

Anita Trupiano

Role: primary

Role: primary

877-275-7724

Tania J Curcio

Role: primary

Tina Czaplinska

Role: primary

Research Nurse Navigator

Role: primary

212-342-5162

Pushpa Talanki

Role: primary

631-638-0815

Quinna Lawson

Role: primary

Sarah Gollwitzer

Role: primary

Cancer Answer Line

Role: primary

866-223-8100

Hanna Cordes

Role: primary

Cynthia Lowery

Role: primary

Jessica Ritter

Role: primary

Camilla Ludlow

Role: backup

Ask Sarah

Role: primary

844-482-4812

Amy Hammack

Role: primary

Phase I Team

Role: primary

214-648-7097

Ramya Ganesh

Role: primary

713-792-5640

UW Cancer Connect

Role: primary

800-622-8922

Medical College of WI Cancer Center Clinical Trials Office

Role: primary

414-805-8900

Other Identifiers

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KO-MEN-007

Identifier Type: -

Identifier Source: org_study_id

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