Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia

NCT ID: NCT06001788

Last Updated: 2025-11-10

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

171 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-22

Study Completion Date

2027-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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AML AML With Mutated NPM1 Hematologic Malignancy KMT2Ar NPM1 Mutation MLL Rearrangement Leukemia Acute Myeloid Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Acute Leukemia Neoplasms by Histologic Type

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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Phase 1b

Oral ziftomenib; Following the determination of the maximum tolerated dose in Phase 1a, participants will be enrolled in 1 of 5 dose validation/expansion cohorts:

A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA

A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC)

A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib

B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA

B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC)

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral administration

Fludarabine

Intervention Type DRUG

Intravenous infusion

Idarubicin

Intervention Type DRUG

Intravenous infusion

Cytarabine

Intervention Type DRUG

Intravenous Infusion

Gilteritinib

Intervention Type DRUG

Oral administration

Granulocyte colony-stimulating factor

Intervention Type BIOLOGICAL

Subcutaneous injection

Phase 1a

Oral ziftomenib; sequential cohorts of escalating dose levels of ziftomenib to identify the safety and tolerability of the combination regimens. Participants will be enrolled in 1 of 5 dose escalation cohorts:

A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA

A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC)

A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib

B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA

B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC)

Group Type EXPERIMENTAL

Ziftomenib

Intervention Type DRUG

Oral administration

Fludarabine

Intervention Type DRUG

Intravenous infusion

Idarubicin

Intervention Type DRUG

Intravenous infusion

Cytarabine

Intervention Type DRUG

Intravenous Infusion

Gilteritinib

Intervention Type DRUG

Oral administration

Granulocyte colony-stimulating factor

Intervention Type BIOLOGICAL

Subcutaneous injection

Interventions

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Ziftomenib

Oral administration

Intervention Type DRUG

Fludarabine

Intravenous infusion

Intervention Type DRUG

Idarubicin

Intravenous infusion

Intervention Type DRUG

Cytarabine

Intravenous Infusion

Intervention Type DRUG

Gilteritinib

Oral administration

Intervention Type DRUG

Granulocyte colony-stimulating factor

Subcutaneous injection

Intervention Type BIOLOGICAL

Other Intervention Names

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KO-539 Xospata

Eligibility Criteria

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Inclusion Criteria

* Has been diagnosed with relapsed/refractory AML.
* Has a documented NPM1 mutation or KMT2A rearrangement.
* Has a documented FLT3 mutation (cA-3 only).
* Has an Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2.
* Has adequate hepatic and renal function as defined per protocol.
* Has an ejection fraction above a protocol defined limit.
* Participant, or legally authorized representative, must be able to understand and provide written informed consent prior to the first screening procedure.
* Has agreed to use contraception as defined per protocol.

Exclusion Criteria

* Has a diagnosis of acute promyelocytic leukemia or blast chronic myeloid leukemia.
* Has clinically active central nervous system leukemia.
* Has an active and uncontrolled infection.
* Has a mean corrected QT interval (QTcF) \> 480ms.
* Has uncontrolled intercurrent illness, including, but not limited to protocol defined cardiac disease.
* Has received radiation, chemotherapy, immunotherapy, or any other anticancer therapy including investigational therapy \<14 days or within 5 drug half-lives prior to the first dose of study intervention.
* Has had major surgery within 4 weeks prior to the first dose of study intervention.
* Has received a hematopoietic stem cell transplant (HSCT) and has not previously had adequate recovery per protocol defined criteria.
* Has active graft-versus-host disease (GvHD) and or on immunosuppressive drugs for the treatment of GvHD
* Participant is pregnant or lactating.
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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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

UCLA Health - 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 California San Francisco

San Francisco, California, United States

Site Status RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status RECRUITING

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, 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

Simmons Cancer Institute

Springfield, Illinois, United States

Site Status RECRUITING

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status RECRUITING

The University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

Henry Ford Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status RECRUITING

Northwell Health, LLC PRIME

Lake Success, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Weill Cornell Medical College-NY Presbyterian Hospital

New York, New York, United States

Site Status RECRUITING

Wilmot Cancer Institute, University of Rochester

Rochester, New York, United States

Site Status RECRUITING

Stony Brook Cancer Center

Stony Brook, New York, United States

Site Status RECRUITING

Atrium Health Levine Cancer Center

Charlotte, North Carolina, United States

Site Status RECRUITING

UH Seidman Cancer Center

Cleveland, Ohio, United States

Site Status RECRUITING

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Lehigh Valley Topper Cancer Institute

Allentown, Pennsylvania, United States

Site Status RECRUITING

Prisma Health

Greenville, South Carolina, United States

Site Status RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

University of Vermont

Burlington, Vermont, United States

Site Status RECRUITING

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, United States

Site Status RECRUITING

University of Washington

Seattle, Washington, United States

Site Status RECRUITING

Froedtert & Medical College Clinics

Milwaukee, Wisconsin, United States

Site Status RECRUITING

IRCCS Azienda Ospedaliero-Universitaria do Bologna - Policlinico di Sant'Orsola

Bologna, , Italy

Site Status RECRUITING

Ospedale Santa Maria delle Croci

Ravenna, , Italy

Site Status RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Site Status RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Central de Asturias

Oviedo, , Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status RECRUITING

Hospital Universitari y Politecnic La Fe

Valencia, , Spain

Site Status RECRUITING

Countries

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United States Italy Spain

Central Contacts

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Kura Medical Information

Role: CONTACT

Phone: 844-KURAONC (844-587-2662)

Email: [email protected]

Facility Contacts

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Role: primary

Christine Duran

Role: primary

Bruck Habtemariam

Role: primary

Research Line

Role: primary

New Patient Contact

Role: primary

Farah Fasihuddin

Role: primary

Gigi Stoneback

Role: primary

Amanda Spires

Role: primary

Role: primary

Esteban Orozco Espiricueta

Role: primary

Mohammed Hussain

Role: primary

Grerk Sutamtewagul

Role: primary

KUCC Navigation Team

Role: primary

Cathy Galasso

Role: primary

Kristyn Dailey

Role: primary

Oncology Clinical Reference Referral Office

Role: primary

Role: primary

Role: primary

Tania Curcio

Role: primary

Clinical Trials Referral Office

Role: primary

Zita Makselyte

Role: primary

Chari Granger

Role: primary

Leslie Ortega

Role: primary

Cynthia J Lowery

Role: primary

Alexandra Bauman

Role: primary

Lisa Johnson

Role: primary

Fiona Davidson

Role: backup

Recruitment and Eligibility Office

Role: primary

Christine Terraciano

Role: primary

Ann Mosely

Role: primary

Stephanie Stahl

Role: primary

Avani Hopkins

Role: primary

Cristina Papayannidis

Role: primary

Francesco Lanza

Role: primary

Simona Sica

Role: primary

Olga Salamero

Role: primary

Teresa Bernal del Castillo

Role: primary

Eduardo Rodríguez-Arbolí

Role: primary

Pau Montesinos Fernandez

Role: primary

Other Identifiers

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KO-MEN-008

Identifier Type: -

Identifier Source: org_study_id