Acute Myeloid Leukemia (AML)
Conditions
Brief summary
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
DRUGziftomenib
Oral adminitration once daily
Sponsors
Kyowa Kirin Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | Cycle 1 Day 1, and Cycle 2 Day 1 (each cycle is 28 days) | AUC0-τ of ziftomenib and its metabolites |
| Maximum plasma concentration (Cmax) | Cycle 1 Day 1, and Cycle 2 Day 1 (each cycle is 28 days) | Cmax of ziftomenib and its metabolites |
| Time to observed maximum plasma concentration (Tmax) | Cycle 1 Day 1, and Cycle 2 Day 1 (each cycle is 28 days) | Tmax of ziftomenib and its metabolites |
Countries
Japan
Contacts
CONTACTKyowa Kirin, Inc.
CONTACTKyowa Kirin Co., Ltd.
Outcome results
None listed