Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Purpose
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.
Conditions
- 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
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Has been diagnosed with relapsed/refractory AML. - Has a documented NPM1 mutation or KMT2A rearrangement. - Has a documented FLT3 mutation (cohort A-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.
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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Phase 1a |
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) |
|
|
Experimental Phase 1b |
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) |
|
Recruiting Locations
The University of Kansas
Kansas City, Kansas 66160
Kansas City, Kansas 66160
More Details
- Status
- Recruiting
- Sponsor
- Kura Oncology, Inc.