Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia
ID: NCT06001788
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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.
Oral administration
Intravenous infusion
Intravenous infusion
Intravenous Infusion
Oral administration
Subcutaneous injection
Treatment Arms Description
Oral ziftomenib; sequential cohorts of escalating dose levels of ziftomenib to identify the safety and tolerability of the combination regimens. Participants will be enrolled in 1 of 5 dose escalation cohorts: A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC) A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC)
Oral ziftomenib; Following the determination of the maximum tolerated dose in Phase 1a, participants will be enrolled in 1 of 5 dose validation/expansion cohorts: A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC) A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC)
- 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.
- 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.
Primary Outcome Measures
- Rate of dose limiting toxicities (DLTs) per dose level — Time Frame: 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 — Time Frame: 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
View Secondary Outcome Measures (20)
- Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2 — Time Frame: 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 — Time Frame: Up to 12 months following discontinuation of treatment
Assessed by ELN 2022 criteria
- Composite complete remission (CRc) rate — Time Frame: Up to 12 months following discontinuation of treatment
Assessed by ELN 2022 criteria
- Morphologic leukemia-free state (MLFS) rate — Time Frame: Up to 12 months following discontinuation of treatment
Assessed by ELN 2022 criteria
- OS — Time Frame: Up to 12 months following discontinuation of treatment
To assess overall survival
- 6-month OS — Time Frame: Up to 6 months following discontinuation of treatment
To assess proportion of patients alive at 6 months
- Median EFS — Time Frame: Up to 12 months following discontinuation of treatment
To assess median event free survival
- 6-month EFS — Time Frame: Up to 6 months following discontinuation of treatment
To assess 6-month event free survival
- DOR — Time Frame: Up to 12 months following discontinuation of treatment
To assess duration of remission
- MRD assessment — Time Frame: 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
This trial is recruiting at 45 study facilities worldwide. Click below to see if there is a clinic or hospital in your area:
Show All 45 Facilities & Contact Sites
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View Official Medical/Scientific Title
Phase 1 Study to Determine the Safety and Tolerability of Ziftomenib Combinations for the Treatment of KMT2A-rearranged or NPM1-mutant Relapsed/Refractory Acute Myeloid Leukemia