NIPH Clinical Trials Search

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

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Nucleophosmin 1 (NPM1) muted relapsed or refractory acute myeloid leukemia
Date of first enrollment	23/04/2026
Target sample size	6
Countries of recruitment
Study type	Interventional
Intervention(s)	600mg of ziftomenib is administrated orally once daily

Outcome(s)

Primary Outcome

CR+CRh rate

Secondary Outcome

-MRD-negative CR+CRh(CR+CRhMRD-) rate -CR rate -MRD negative CR rate -CRc(CR+ CRh + CRi) rate -MRD negative CRc (CRcMRD-) rate -ORR(CR + CRh + CRi + MLFS+PR) -Transfusion-independent rate -Duration of CR+CRh -Time to CR+CRh -Time to CR -Time to CRc -Time to CR, CRh, Cri, MLFS or PR -EFS -OS -Incidence and severity of adverse events -Incidence of serious adverse events -Death during treatment with ziftomenib -Discontinuation of ziftomenib due to adverse events -Clinically significant changes in clinical laboratory values, vital signs, and ECG parameters -Clinically significant decrease in ECOG PS -Plasma concentrations of ziftomenib and metabolites -PK parameters

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Both
Include criteria	1. Patients who have voluntarily given written informed consent to participate in the study and are willing to follow all specified requirements and procedures. 2. Patients 18 years or older at the time of informed consent. 3. Patients with a confirmed diagnosis of AML (any form of presentation). 4. Patients who meet the following definitions of relapsed or refractory. Relapsed: CR, CRh or those who achieved CRi who experienced any of the following recurrent symptoms. -Bone marrow blasts >=5% -Blood blasts reappear in peripheral blood samples collected twice at least one week apart Refractory: Patients who did not achieve CR, CRh or CRi after adequate period of initial intensive chemotherapy or initial treatment with non-intensive chemotherapy, such as venetoclax or demethylation inhibitors. 5. Patients considered to have no standard treatment with sustained remission, patients who could not complete potentially curative treatment, patients with no treatment that could be expected to be effective, or patients who refused standard treatment. 6. Patients who were confirmed to have NPM1-m by genetic testing. 7. Patients with a ECOG PS of 0-2. 8. Patients with expected survival beyond 2 months. 9. Patients with a pretest WBC count of 30000 per mm3 or less (enrollment is permitted even if the criteria are met by treatment with hydroxyurea prior to enrollment). 10. Patients with hepatic and renal function who meet all of the following criteria at a pretest. Hepatic function: -AST 3.0 times the upper limit of normal or less -ALT 3.0 times the upper limit of normal or less -Bil 1.5 times or less than the upper limit of normal (or 3.0 times or less if considered abnormal due to Gilbert's syndrome or underlying disorder) Renal function: -Cockcroft-Gault equation Clcr more than 30 mL/min -However, if medically appropriate, a eGFR assessment using CKD-EPI creatinine formula (2021 formula) or CKD EPI creatinine cystatin C formula (2021 formula) may be used. In addition, because the CKD-EPI equation tends to overestimate renal function when used for the assessment of Japanese, eGFR is calculated by taking the Japanese factor in each estimation equation as 0.813 and 0.908, respectively (Japanese Society of Nephrology, 2023).
Exclude criteria	1. Those diagnosed with APL. 2. Patients with past documented BCR-ABL mutations. 3. Patients with a history of malignancy requiring treatment within 2 years of enrollment in the study (excluding malignancies listed in the inclusion criteria). However, patients considered cured by topical treatment (e.g., skin cancer other than melanoma, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ) will be eligible to participate in the study. 4. Patients who received donor lymphocyte infusion within 30 days before enrollment. 5. Patients with clinically active CNS leukemia. 6. Subjects who have previously undergone allogeneic hematopoietic stem-cell transplantation and who have not had adequate hematologic recovery (ANC >=1000 per mm3, PLT >=50000 per mm3, and signs of Cellular bone marrow). 7. Patients with active Grade 2 or greater acute GvHD or active severe/moderate chronic GvHDs. In addition, acute GvHD should be evaluated according to MAGIC criteria (Harris et al., 2016) and chronic GvHD should be evaluated according to NIH criteria (Jagasia et al., 2015) for Grade or severity. 8. Patients who have previously received menin inhibitors. 9. Patients who received either chemotherapy, immunotherapy, radiotherapy (unless intended to control CNS leukaemia), hormonal therapy (excluding adjuvant maintenance therapy for breast or prostatic cancer), or other investigational products within 2 weeks prior to Cycle 1 Day 1 or 5 times the half-life of these therapies, whichever is shorter. 10. Subjects whose adverse events have not resolved below Grade 1 due to previous antineoplastic treatment. However, if the principal investigator or the subinvestigator judges that there is no effect on the safety assessment of test subjects in subjects with alopecia and laboratory abnormalities within the ranges listed in the inclusion criteria or Grade 2 chronic adverse events, they will be enrolled in the clinical trial after discussion with the sponsor. 11. Patients requiring treatment with CYP3A4 potent or moderate inducers, except for antibiotic drugs, antifungals, and antivirals used as standard-of-care to prevent infections. Drugs considered to be essential for the treatment of patients should be discussed individually with the sponsor. 12. Patients with a positive pretest result for either HBV antigen or antibody, HCV antibody, or HIV antibody. However, enrollment in the study is permitted in the following cases. -If HBV test at the pre-test is negative for HBs antigen and positive for either HBc antibody or HBs antibody or both, but below the lower limit of quantitation or 20 IU/mL(1.3 LogIU/mL in HBV-DNA test -If hepatitis-B vaccination history is evident and HBs antibody-only positive -If HCV antibody test at pre-test is positive for HCV antibody, but negative for HCV nucleic acid amplified test (HCV-RNA test) -If HIV antibody test at pre-test is positive for HIV antibody, but negative for HIV diffusion-amplification test (HIV-RNA test) 13. Patients with a history of disease predisposing to serious or life-threatening infections (e.g., cystic fibrosis, congenital or acquired immunodeficiency, hemorrhagic disease, cytopenia not related to the primary disease). 14. Patients with active, uncontrol acute or chronic systemic fungal, bacterial, virus, or other infections. 15. Patients with current or previous interstitial lung disease. 16. Patients with any of the following current or past diseases. -Serious cardiovascular disease such as unstable angina, uncontrolled hypertension, and arrhythmias -History of cerebrovascular disorder including transient ischemic attack, serious cardiovascular disease including myocardial infarction, congestive heart failure related to primary heart disease (NYHA class-related III or IV), or ischemic or severe valvular heart disease within 6 months prior to obtaining informed consent 17. The mean QTcF (Fredericia equation) of three ECG examinations performed in 5 minutes or less exceeds 480 msec. However, if the fascicular block or QRS interval exceeds 120 msec, the corrected QTcF should be calculated using appropriate methods (e.g., assessment by a cardiologist, assessment by Bogossian Abbreviated Formula (QTc=QT-0.5*QRS)) to assess eligibility. 18. Those who underwent major surgical procedures in the 4 weeks prior to Cycle 1 Day 1. Patients who undergo operations requiring local/epidural anaesthesia should be enrolled if they have been completed at least 72 hours prior to Cycle 1 Day 1 and recovered. 19. Patients with underlying medical conditions that, at the discretion of the principal investigator or the subinvestigator, are likely to have clearly adverse ziftomenib dose or obscure assessment after ziftomenib administration. 20. Patients who are pregnant, breastfeeding (excluded from the target even if breastfeeding is interrupted), or possibly pregnant, or who wish to become pregnant during the study period. 21. Patients with mental illness, central nerve illness (e.g., encephalopathy), or social conditions for whom compliance with the study is difficult or is judged to affect document informed consent. 22. In addition, patients who are judged by the principal investigator or the subinvestigator to be unfavorable for participating in the study.