AML, AML With Mutated NPM1, Hematologic Malignancy, KMT2Ar, NPM1 Mutation, MLL Rearrangement, Leukemia, Acute Myeloid Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute, Acute Leukemia, Neoplasms by Histologic Type
Conditions
Brief summary
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.
Interventions
DRUGZiftomenib
Oral administration
DRUGFludarabine
Intravenous infusion
DRUGIdarubicin
Intravenous infusion
DRUGCytarabine
Intravenous Infusion
DRUGGilteritinib
Oral administration
BIOLOGICALGranulocyte colony-stimulating factor
Subcutaneous injection
Sponsors
Kura Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of dose limiting toxicities (DLTs) per dose level | During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle) | Assessed by the NCI-CTCAE v5.0 |
| Descriptive statistics of adverse events | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2 | Up to 12 months following discontinuation of treatment | Assessed by ELN 2022 criteria |
| Complete remission (CR) / Complete remission with partial hematologic recovery (CRh) rate for cohort A-3 | Up to 12 months following discontinuation of treatment | Assessed by ELN 2022 criteria |
| Composite complete remission (CRc) rate | Up to 12 months following discontinuation of treatment | Assessed by ELN 2022 criteria |
| Morphologic leukemia-free state (MLFS) rate | Up to 12 months following discontinuation of treatment | Assessed by ELN 2022 criteria |
| OS | Up to 12 months following discontinuation of treatment | To assess overall survival |
| 6-month OS | Up to 6 months following discontinuation of treatment | To assess proportion of patients alive at 6 months |
| Median EFS | Up to 12 months following discontinuation of treatment | To assess median event free survival |
| 6-month EFS | Up to 6 months following discontinuation of treatment | To assess 6-month event free survival |
| DOR | Up to 12 months following discontinuation of treatment | To assess duration of remission |
| MRD assessment | 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 |
| HSCT | Up to 12 months following discontinuation of treatment | To assess proportion of patients that undergo a hematopoietic stem-cell transplant |
| Transfusion independence | Up to 12 months following discontinuation of treatment | To assess rate of transfusion independence |
| Ziftomenib Cmax | Cycle 1 (Each cycle is 28 days) | To assess the maximum plasma combination of ziftomenib and its metabolites |
| Ziftomenib Tmax | Cycle 1 (Each cycle is 28 days) | To assess the time to observed maximum plasma concentration of ziftomenib and its metabolites |
| Ziftomenib AUC(0-last) | 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 |
| Ziftomenib AUC(tau) | 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 |
| Gilteritinib Cmax | Cycle 1 (Each cycle is 28 days) | To assess the maximum plasma combination of gilteritinib |
| Gilteritinib Tmax | Cycle 1 (Each cycle is 28 days) | To assess the time to observed maximum plasma concentration of gilteritinib |
| Gilteritinib AUC(0-last) | 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 |
| Gilteritinib AUC(tau) | Cycle 1 (Each cycle is 28 days) | To assess the area under the plasma concentration-time-curve over a dosing interval for gilteritinib |
Countries
Italy, Spain, United States
Contacts
Primary ContactKura Medical Information
Outcome results
None listed