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

April 10, 2026 updated by: Kura Oncology, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

171

Phase

  • Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Bologna, Italy, 40138
        • Recruiting
        • IRCCS Azienda Ospedaliero-Universitaria do Bologna - Policlinico di Sant'Orsola
        • Contact:
      • Ravenna, Italy, 48121
      • Roma, Italy, 00168
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
        • Contact:
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall d'Hebron
        • Contact:
      • Oviedo, Spain, 33011
        • Recruiting
        • Hospital Universitario Central de Asturias
        • Contact:
      • Seville, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocio
        • Contact:
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitari y Politecnic La Fe
        • Contact:
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
    • California
      • Los Angeles, California, United States, 90089
        • Recruiting
        • USC Norris Comprehensive Cancer Center
        • Contact:
      • Los Angeles, California, United States, 90095
      • Orange, California, United States, 92868
        • Recruiting
        • UC Irvine Health Chao Family Comprehensive Cancer Center
        • Contact:
      • San Francisco, California, United States, 94115
        • Recruiting
        • University of California San Francisco
    • Colorado
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Recruiting
        • Smilow Cancer Hospital at Yale New Haven
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
      • Augusta, Georgia, United States, 30912
        • Recruiting
        • Georgia Cancer Center at Augusta University
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
        • Contact:
      • Maywood, Illinois, United States, 60153
        • Recruiting
        • Loyola University Medical Center
        • Contact:
      • Springfield, Illinois, United States, 62702
        • Withdrawn
        • Simmons Cancer Institute
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa Hospitals & Clinics
        • Contact:
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • The University of Kansas Cancer Center
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48201
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Cancer Institute
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Contact:
          • Michael Haddadin, MBBS
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • John Theurer Cancer Center at Hackensack University Medical Center
        • Contact:
    • New York
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Comprehensive Cancer Center
        • Contact:
      • Lake Success, New York, United States, 11042
        • Recruiting
        • Northwell Health, LLC PRIME
      • New York, New York, United States, 10021
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Phone Number: 646-888-4167
      • New York, New York, United States, 10065
        • Recruiting
        • Weill Cornell Medical College-NY Presbyterian Hospital
        • Contact:
      • Rochester, New York, United States, 14642
        • Recruiting
        • Wilmot Cancer Institute, University of Rochester
        • Contact:
      • Stony Brook, New York, United States, 11794
    • North Carolina
      • Charlotte, North Carolina, United States, 60201
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • UH Seidman Cancer Center
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Withdrawn
        • Lehigh Valley Topper Cancer Institute
    • South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center
        • Contact:
          • Recruitment and Eligibility Office
          • Phone Number: 800-811-8480
          • Email: cip@vumc.org
    • Texas
      • Dallas, Texas, United States, 75246
      • Houston, Texas, United States, 77030
    • Vermont
      • Burlington, Vermont, United States, 05401
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia Comprehensive Cancer Center
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • University of Washington
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Froedtert & Medical College Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key 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.

Key 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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)
Drug: Fludarabine
Intravenous infusion
Drug: Ziftomenib
Oral administration
Other Names:
  • KO-539
Drug: Idarubicin
Intravenous infusion
Drug: Cytarabine
Intravenous Infusion
Drug: Gilteritinib
Oral administration
Other Names:
  • Xospata
Biological: Granulocyte colony-stimulating factor
Subcutaneous injection
Experimental: 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)
Drug: Fludarabine
Intravenous infusion
Drug: Ziftomenib
Oral administration
Other Names:
  • KO-539
Drug: Idarubicin
Intravenous infusion
Drug: Cytarabine
Intravenous Infusion
Drug: Gilteritinib
Oral administration
Other Names:
  • Xospata
Biological: Granulocyte colony-stimulating factor
Subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Descriptive statistics of adverse events
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
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
Rate of dose limiting toxicities (DLTs) per dose level
Time Frame: During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle)
Assessed by the NCI-CTCAE v5.0
During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Assessed by ELN 2022 criteria
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
Assessed by ELN 2022 criteria
Up to 12 months following discontinuation of treatment
Composite complete remission (CRc) rate
Time Frame: Up to 12 months following discontinuation of treatment
Assessed by ELN 2022 criteria
Up to 12 months following discontinuation of treatment
Morphologic leukemia-free state (MLFS) rate
Time Frame: Up to 12 months following discontinuation of treatment
Assessed by ELN 2022 criteria
Up to 12 months following discontinuation of treatment
OS
Time Frame: Up to 12 months following discontinuation of treatment
To assess overall survival
Up to 12 months following discontinuation of treatment
6-month OS
Time Frame: Up to 6 months following discontinuation of treatment
To assess proportion of patients alive at 6 months
Up to 6 months following discontinuation of treatment
Median EFS
Time Frame: Up to 12 months following discontinuation of treatment
To assess median event free survival
Up to 12 months following discontinuation of treatment
6-month EFS
Time Frame: Up to 6 months following discontinuation of treatment
To assess 6-month event free survival
Up to 6 months following discontinuation of treatment
DOR
Time Frame: Up to 12 months following discontinuation of treatment
To assess duration of remission
Up to 12 months following discontinuation of treatment
HSCT
Time Frame: Up to 12 months following discontinuation of treatment
To assess proportion of patients that undergo a hematopoietic stem-cell transplant
Up to 12 months following discontinuation of treatment
Ziftomenib Cmax
Time Frame: Cycle 1 (Each cycle is 28 days)
To assess the maximum plasma combination of ziftomenib and its metabolites
Cycle 1 (Each cycle is 28 days)
Ziftomenib Tmax
Time Frame: Cycle 1 (Each cycle is 28 days)
To assess the time to observed maximum plasma concentration of ziftomenib and its metabolites
Cycle 1 (Each cycle is 28 days)
Ziftomenib AUC(0-last)
Time Frame: Cycle 1 (Each cycle is 28 days)
To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of ziftomenib and its metabolites
Cycle 1 (Each cycle is 28 days)
Ziftomenib AUC(tau)
Time Frame: Cycle 1 (Each cycle is 28 days)
To assess the area under the plasma concentration-time-curve over a dosing interval for ziftomenib and its metabolites
Cycle 1 (Each cycle is 28 days)
Gilteritinib Cmax
Time Frame: Cycle 1 (Each cycle is 28 days)
To assess the maximum plasma combination of gilteritinib
Cycle 1 (Each cycle is 28 days)
Gilteritinib Tmax
Time Frame: Cycle 1 (Each cycle is 28 days)
To assess the time to observed maximum plasma concentration of gilteritinib
Cycle 1 (Each cycle is 28 days)
Gilteritinib AUC(0-last)
Time Frame: Cycle 1 (Each cycle is 28 days)
To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of gilteritinib
Cycle 1 (Each cycle is 28 days)
Gilteritinib AUC(tau)
Time Frame: Cycle 1 (Each cycle is 28 days)
To assess the area under the plasma concentration-time-curve over a dosing interval for gilteritinib
Cycle 1 (Each cycle is 28 days)
MRD assessment
Time Frame: Up to 12 months following discontinuation of treatment
To assess minimum residual disease in bone marrow as assessed by multiparameter flow cytometry (MFC) and molecular analysis
Up to 12 months following discontinuation of treatment
Transfusion independence
Time Frame: Up to 12 months following discontinuation of treatment
To assess rate of transfusion independence
Up to 12 months following discontinuation of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kura Oncology, Inc.

Investigators

  • Study Director: Clinical Development, Kura Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 22, 2024

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

August 7, 2023

First Submitted That Met QC Criteria

August 14, 2023

First Posted (Actual)

August 21, 2023

Study Record Updates

Last Update Posted (Actual)

April 14, 2026

Last Update Submitted That Met QC Criteria

April 10, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KO-MEN-008

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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