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

Official title

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

Overview

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

Interventions

• Drug ziftomenib
  Oral adminitration once daily

Primary outcome measures

• CR+CRh rate [Time frame: Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks]

Secondary outcome measures (12)

• MRD-negative CR+CRh (CR+CRhMRD-) rate [Time frame: Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks]
• CR rate [Time frame: Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks]
• MRD-negative CR rate [Time frame: Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks]
• CRc (CR+ CRh + CRi) rate [Time frame: Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks]
• MRD-negative CRc (CRcMRD-) rate [Time frame: 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) [Time frame: Best overall response assessed every 28 days from first dose until disease progression or withdrawall, an average of 16weeks]
• Transfusion independence rate [Time frame: 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 [Time frame: Every 28 days from first dose until disease progression or withdrawall, an average of 16weeks]
• Time to CR+CRh [Time frame: Every 28 days from first dose until disease progression or withdrawall, an average of 16weeks]
• Time to CR [Time frame: Every 28 days from first dose until disease progression or withdrawall, an average of 16weeks]
• Time to CRc [Time frame: Every 28 days from first dose until disease progression or withdrawall, an average of 16weeks]
• Time to CR, CRh, Cri, MLFS or PR [Time frame: Every 28 days from first dose until disease progression or withdrawall, an average of 16weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 20 centers

• Chiba Aoba Municipal Hospital — Chiba
• Gifu Municipal Hospital — Gifu
• Hyogo Medical University Hospital — Hyōgo
• Mito Medical Center — Ibaraki
• Imamura General Hospital — Kagoshima
• Kanagawa Cancer Center — Kanagawa
• Kyoto University Hospital — Kyoto
• Tohoku University Hospital — Miyagi
• … and 12 more centers

Identifiers

NCT: NCT07623616 · KO-MEN-J001 · jRCT2031250550

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗