search
Back to results

Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Primary Purpose

AML, AML With Mutated NPM1, Hematologic Malignancy

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Ziftomenib
Fludarabine
Idarubicin
Cytarabine
Gilteritinib
Granulocyte colony-stimulating factor
Sponsored by
Kura Oncology, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for AML

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key 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. 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Phase 1a

    Phase 1b

    Arm 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)

    Outcomes

    Primary Outcome Measures

    Rate of dose limiting toxicities (DLTs) per dose level
    Assessed by the NCI-CTCAE v5.0
    Descriptive statistics of adverse events
    Assessed by the NCI-CTCAE v5.0

    Secondary Outcome Measures

    Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2
    Assessed by ELN 2022 criteria
    Complete remission (CR) / Complete remission with partial hematologic recovery (CRh) rate for cohort A-3
    Assessed by ELN 2022 criteria
    Composite complete remission (CRc) rate
    Assessed by ELN 2022 criteria
    Morphologic leukemia-free state (MLFS) rate
    Assessed by ELN 2022 criteria
    OS
    To assess overall survival
    6-month OS
    To assess proportion of patients alive at 6 months
    Median EFS
    To assess median event free survival
    6-month EFS
    To assess 6-month event free survival
    DOR
    To assess duration of remission
    MRD assessment
    To assess minimum residual disease in bone marrow
    HSCT
    To assess proportion of patients that undergo a hematopoietic stem-cell transplant
    Transfusion independence
    To assess transfusion independence
    Ziftomenib Cmax
    To assess the maximum plasma combination of ziftomenib and its metabolites
    Ziftomenib Tmax
    To assess the time to observed maximum plasma concentration of ziftomenib and its metabolites
    Ziftomenib AUC(0-last)
    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)
    To assess the area under the plasma concentration-time-curve over a dosing interval for ziftomenib and its metabolites
    Gilteritinib Cmax
    To assess the maximum plasma combination of gilteritinib
    Gilteritinib Tmax
    To assess the time to observed maximum plasma concentration of gilteritinib
    Gilteritinib AUC(0-last)
    To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of gilteritinib
    Gilteritinib AUC(tau)
    To assess the area under the plasma concentration-time-curve over a dosing interval for gilteritinib

    Full Information

    First Posted
    August 7, 2023
    Last Updated
    August 14, 2023
    Sponsor
    Kura Oncology, Inc.
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT06001788
    Brief Title
    Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia
    Official 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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 2023 (Anticipated)
    Primary Completion Date
    August 2026 (Anticipated)
    Study Completion Date
    August 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Kura Oncology, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    171 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Phase 1a
    Arm Type
    Experimental
    Arm 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)
    Arm Title
    Phase 1b
    Arm Type
    Experimental
    Arm Description
    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)
    Intervention Type
    Drug
    Intervention Name(s)
    Ziftomenib
    Other Intervention Name(s)
    KO-539
    Intervention Description
    Oral administration
    Intervention Type
    Drug
    Intervention Name(s)
    Fludarabine
    Intervention Description
    Intravenous infusion
    Intervention Type
    Drug
    Intervention Name(s)
    Idarubicin
    Intervention Description
    Intravenous infusion
    Intervention Type
    Drug
    Intervention Name(s)
    Cytarabine
    Intervention Description
    Intravenous Infusion
    Intervention Type
    Drug
    Intervention Name(s)
    Gilteritinib
    Other Intervention Name(s)
    Xospata
    Intervention Description
    Oral administration
    Intervention Type
    Biological
    Intervention Name(s)
    Granulocyte colony-stimulating factor
    Intervention Description
    Subcutaneous injection
    Primary Outcome Measure Information:
    Title
    Rate of dose limiting toxicities (DLTs) per dose level
    Description
    Assessed by the NCI-CTCAE v5.0
    Time Frame
    During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle)
    Title
    Descriptive statistics of adverse events
    Description
    Assessed by the NCI-CTCAE v5.0
    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
    Secondary Outcome Measure Information:
    Title
    Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2
    Description
    Assessed by ELN 2022 criteria
    Time Frame
    Up to 12 months following discontinuation of treatment
    Title
    Complete remission (CR) / Complete remission with partial hematologic recovery (CRh) rate for cohort A-3
    Description
    Assessed by ELN 2022 criteria
    Time Frame
    Up to 12 months following discontinuation of treatment
    Title
    Composite complete remission (CRc) rate
    Description
    Assessed by ELN 2022 criteria
    Time Frame
    Up to 12 months following discontinuation of treatment
    Title
    Morphologic leukemia-free state (MLFS) rate
    Description
    Assessed by ELN 2022 criteria
    Time Frame
    Up to 12 months following discontinuation of treatment
    Title
    OS
    Description
    To assess overall survival
    Time Frame
    Up to 12 months following discontinuation of treatment
    Title
    6-month OS
    Description
    To assess proportion of patients alive at 6 months
    Time Frame
    Up to 6 months following discontinuation of treatment
    Title
    Median EFS
    Description
    To assess median event free survival
    Time Frame
    Up to 12 months following discontinuation of treatment
    Title
    6-month EFS
    Description
    To assess 6-month event free survival
    Time Frame
    Up to 6 months following discontinuation of treatment
    Title
    DOR
    Description
    To assess duration of remission
    Time Frame
    Up to 12 months following discontinuation of treatment
    Title
    MRD assessment
    Description
    To assess minimum residual disease in bone marrow
    Time Frame
    Up to 12 months following discontinuation of treatment
    Title
    HSCT
    Description
    To assess proportion of patients that undergo a hematopoietic stem-cell transplant
    Time Frame
    Up to 12 months following discontinuation of treatment
    Title
    Transfusion independence
    Description
    To assess transfusion independence
    Time Frame
    Up to 12 months following discontinuation of treatment
    Title
    Ziftomenib Cmax
    Description
    To assess the maximum plasma combination of ziftomenib and its metabolites
    Time Frame
    Cycle 1 (Each cycle is 28 days)
    Title
    Ziftomenib Tmax
    Description
    To assess the time to observed maximum plasma concentration of ziftomenib and its metabolites
    Time Frame
    Cycle 1 (Each cycle is 28 days)
    Title
    Ziftomenib AUC(0-last)
    Description
    To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of ziftomenib and its metabolites
    Time Frame
    Cycle 1 (Each cycle is 28 days)
    Title
    Ziftomenib AUC(tau)
    Description
    To assess the area under the plasma concentration-time-curve over a dosing interval for ziftomenib and its metabolites
    Time Frame
    Cycle 1 (Each cycle is 28 days)
    Title
    Gilteritinib Cmax
    Description
    To assess the maximum plasma combination of gilteritinib
    Time Frame
    Cycle 1 (Each cycle is 28 days)
    Title
    Gilteritinib Tmax
    Description
    To assess the time to observed maximum plasma concentration of gilteritinib
    Time Frame
    Cycle 1 (Each cycle is 28 days)
    Title
    Gilteritinib AUC(0-last)
    Description
    To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of gilteritinib
    Time Frame
    Cycle 1 (Each cycle is 28 days)
    Title
    Gilteritinib AUC(tau)
    Description
    To assess the area under the plasma concentration-time-curve over a dosing interval for gilteritinib
    Time Frame
    Cycle 1 (Each cycle is 28 days)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Key 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. 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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Clinical Operations
    Phone
    617 588 3755
    Email
    KO-MEN-008@kuraoncology.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Clinical Development
    Organizational Affiliation
    Kura Oncology
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia

    We'll reach out to this number within 24 hrs