A Phase 2 Clinical Study of Ziftomenib in Patients With Relapsed or Refractory NPM1-Mutated Acute Myeloid Leukemia

A Phase 2, Multicenter, Open-Label Study of Ziftomenib Monotherapy in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia With NPM1 Mutation

This is the first study to administer ziftomenib to Japanese patients. In this study, the efficacy, safety, and pharmacokinetics of ziftomenib will be evaluated in patients with relapsed or refractory NPM1-mutated acute myeloid leukemia

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: ziftomenib

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kyowa Kirin Co., Ltd.; Email: clinical.info.jp@kyowakirin.com
• Study Contact Backup: Name: Kyowa Kirin, Inc.; Phone Number: 1-609-919-1100; Email: kkd.clintrial.82@kyowakirin.com

Study Locations

• Japan
  • Chiba, Japan
    • Recruiting
    • Chiba Aoba Municipal Hospital
  • Gifu, Japan
    • Recruiting
    • Gifu Municipal Hospital
  • Hyōgo, Japan
    • Not yet recruiting
    • Hyogo Medical University Hospital
  • Ibaraki, Japan
    • Recruiting
    • Mito Medical Center
  • Kagoshima, Japan
    • Recruiting
    • Imamura General Hospital
  • Kanagawa, Japan
    • Recruiting
    • Kanagawa cancer center
  • Kyoto, Japan
    • Not yet recruiting
    • Kyoto University Hospital
  • Miyagi, Japan
    • Recruiting
    • Tohoku University Hospital
  • Nagano, Japan
    • Recruiting
    • Matsumoto National Hospital
  • Nagasaki, Japan
    • Recruiting
    • Nagasaki University Hospital
  • Okayama, Japan
    • Recruiting
    • Okayama University Hospital
  • Okayama, Japan
    • Recruiting
    • Kurashiki Central Hospital
  • Osaka, Japan
    • Recruiting
    • Osaka Metropolitan university Hospital
  • Osaka, Japan
    • Recruiting
    • Kansai Medical University Hospital
  • Saitama, Japan
    • Not yet recruiting
    • Jichi Medical University Saitama Medical Center
  • Tochigi, Japan
    • Recruiting
    • Dokkyo Medical University Hospital
  • Tochigi, Japan
    • Recruiting
    • Jichi Medical University Hospital
  • Tokyo, Japan
    • Recruiting
    • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
  • Tokyo, Japan
    • Not yet recruiting
    • Keio University Hospital
  • Tokyo, Japan
    • Not yet recruiting
    • Nippon Medical School Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntary written informed consent and willingness to comply with all study procedures
• Age ≥ 18 years
• Confirmed diagnosis of acute myeloid leukemia (AML)
• Patients with R/R AML with NPM1-m
• No available standard of care expected to provide clinical benefit, ineligible for or declined standard therapy.
• ECOG performance status 0-2.
• White blood cell count ≤ 30,000/mm³ at screening (hydroxyurea permitted for cytoreduction).
• Adequate organ function according to protocol requirements.
• Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 187 days after the last dose of study treatment.
• Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 97 days after the last dose of study treatment.

Exclusion Criteria:

• Diagnosis of acute promyelocytic leukemia.
• Donor lymphocyte infusion < 30 days prior to study entry.
• Clinically active central nervous system (CNS) leukemia.
• Prior hematopoietic stem cell transplantation (HSCT) without adequate hematologic recovery.
• Active Grade ≥ 2 acute graft-versus-host disease or moderate/severe chronic graft-versus-host disease.
• Prior treatment with a menin inhibitor.
• Receipt of chemotherapy, immunotherapy, radiotherapy, or investigational therapy within 14 days or 5 half-lives prior to first dose.
• Unresolved toxicities from prior therapy > Grade 1.
• Requirement for strong CYP3A4 inducers.
• Active or uncontrolled infection, including hepatitis B, hepatitis C, or HIV.
• Conditions predisposing to serious or life-threatening infection or significant immunodeficiency.
• Cardiovascular disease or QTcF > 480 ms.
• Interstitial lung disease.
• Major surgery within 4 weeks prior to first dose.
• Women who are pregnant or lactating
• Any medical, psychiatric, or social condition that may interfere with study participation or safety, or that makes the patient unsuitable in the investigator's judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ziftomenib; Oral adminitration once daily	Drug: ziftomenib; Oral adminitration once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
CR+CRh rate	Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRD-negative CR+CRh (CR+CRhMRD-) rate		Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
CR rate		Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
MRD-negative CR rate		Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
CRc (CR+ CRh + CRi) rate		Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
MRD-negative CRc (CRcMRD-) rate		Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
ORR (CR + CRh + CRi + MLFS + PR)		Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
Transfusion independence rate		From the day after first dose through the last dose before initiation of subsequent therapy (including hematopoietic stem cell transplantation)l, an average of 16weeks
Duration of CR+CRh		Every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
Time to CR+CRh		Every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
Time to CR		Every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
Time to CRc		Every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
Time to CR, CRh, Cri, MLFS or PR		Every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
EFS		Every 28 days from first dose until disease progression or withdrawall, an average of 16weeks
OS		During the treatment and every 90 days after study treatment completion (approximately up to 1 year after study treatment completion)
Incidence and severity of adverse events		During treatment and up to approximately 28 days after treatment discontinuation
Incidence of serious adverse events		During treatment and up to approximately 28 days after treatment discontinuation
Death during treatment with ziftomenib		During the treatment
Discontinuation of ziftomenib due to adverse events		During the treatment
Clinically significant changes in clinical laboratory values, vital signs, and ECG parameters		During treatment and up to end of the treatment assessment
Clinically significant decrease in ECOG PS		During treatment and up to end of the treatment assessment
Area under the plasma drug concentration time curve over a dosing interval (AUC0-τ)	AUC0-τ of ziftomenib and its metabolites	Cycle 1 Day 1, and Cycle 2 Day 1 (each cycle is 28 days)
Maximum plasma concentration (Cmax)	Cmax of ziftomenib and its metabolites	Cycle 1 Day 1, and Cycle 2 Day 1 (each cycle is 28 days)
Time to observed maximum plasma concentration (Tmax)	Tmax of ziftomenib and its metabolites	Cycle 1 Day 1, and Cycle 2 Day 1 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute
• Other Study ID Numbers: KO-MEN-J001; jRCT2031250550 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The datasets generated and/or analyzed during the study sponsored by Kyowa Kirin will be available in the Vivli repository, https://vivli.org/ourmember/kyowa-kirin/ as long as conditions of data disclosure specified in the policy section of the Vivli website are satisfied.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No