xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06001788</url>
    </required_header>
    <id_info>
      <org_study_id>KO-MEN-008</org_study_id>
      <nct_id>NCT06001788</nct_id>
    </id_info>
    <brief_title>Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia</brief_title>
    <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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Kura Oncology, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Kura Oncology, Inc.</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The safety, tolerability, and antileukemic response of ziftomenib in combination with&#xD;
        standard of care treatments for patients with relapsed/refractory acute myeloid leukemia will&#xD;
        be examined with the following agents: FLAG-IDA, low-dose cytarabine, and gilteritinib.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 2023</start_date>
    <completion_date type="Anticipated">August 2027</completion_date>
    <primary_completion_date type="Anticipated">August 2026</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>Yes</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Rate of dose limiting toxicities (DLTs) per dose level</measure>
      <time_frame>During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle)</time_frame>
      <description>Assessed by the NCI-CTCAE v5.0</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Descriptive statistics of adverse events</measure>
      <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</time_frame>
      <description>Assessed by the NCI-CTCAE v5.0</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2</measure>
      <time_frame>Up to 12 months following discontinuation of treatment</time_frame>
      <description>Assessed by ELN 2022 criteria</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Complete remission (CR) / Complete remission with partial hematologic recovery (CRh) rate for cohort A-3</measure>
      <time_frame>Up to 12 months following discontinuation of treatment</time_frame>
      <description>Assessed by ELN 2022 criteria</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Composite complete remission (CRc) rate</measure>
      <time_frame>Up to 12 months following discontinuation of treatment</time_frame>
      <description>Assessed by ELN 2022 criteria</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Morphologic leukemia-free state (MLFS) rate</measure>
      <time_frame>Up to 12 months following discontinuation of treatment</time_frame>
      <description>Assessed by ELN 2022 criteria</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>OS</measure>
      <time_frame>Up to 12 months following discontinuation of treatment</time_frame>
      <description>To assess overall survival</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>6-month OS</measure>
      <time_frame>Up to 6 months following discontinuation of treatment</time_frame>
      <description>To assess proportion of patients alive at 6 months</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median EFS</measure>
      <time_frame>Up to 12 months following discontinuation of treatment</time_frame>
      <description>To assess median event free survival</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>6-month EFS</measure>
      <time_frame>Up to 6 months following discontinuation of treatment</time_frame>
      <description>To assess 6-month event free survival</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DOR</measure>
      <time_frame>Up to 12 months following discontinuation of treatment</time_frame>
      <description>To assess duration of remission</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>MRD assessment</measure>
      <time_frame>Up to 12 months following discontinuation of treatment</time_frame>
      <description>To assess minimum residual disease in bone marrow</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>HSCT</measure>
      <time_frame>Up to 12 months following discontinuation of treatment</time_frame>
      <description>To assess proportion of patients that undergo a hematopoietic stem-cell transplant</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Transfusion independence</measure>
      <time_frame>Up to 12 months following discontinuation of treatment</time_frame>
      <description>To assess transfusion independence</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ziftomenib Cmax</measure>
      <time_frame>Cycle 1 (Each cycle is 28 days)</time_frame>
      <description>To assess the maximum plasma combination of ziftomenib and its metabolites</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ziftomenib Tmax</measure>
      <time_frame>Cycle 1 (Each cycle is 28 days)</time_frame>
      <description>To assess the time to observed maximum plasma concentration of ziftomenib and its metabolites</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ziftomenib AUC(0-last)</measure>
      <time_frame>Cycle 1 (Each cycle is 28 days)</time_frame>
      <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</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ziftomenib AUC(tau)</measure>
      <time_frame>Cycle 1 (Each cycle is 28 days)</time_frame>
      <description>To assess the area under the plasma concentration-time-curve over a dosing interval for ziftomenib and its metabolites</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gilteritinib Cmax</measure>
      <time_frame>Cycle 1 (Each cycle is 28 days)</time_frame>
      <description>To assess the maximum plasma combination of gilteritinib</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gilteritinib Tmax</measure>
      <time_frame>Cycle 1 (Each cycle is 28 days)</time_frame>
      <description>To assess the time to observed maximum plasma concentration of gilteritinib</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gilteritinib AUC(0-last)</measure>
      <time_frame>Cycle 1 (Each cycle is 28 days)</time_frame>
      <description>To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of gilteritinib</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gilteritinib AUC(tau)</measure>
      <time_frame>Cycle 1 (Each cycle is 28 days)</time_frame>
      <description>To assess the area under the plasma concentration-time-curve over a dosing interval for gilteritinib</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">171</enrollment>
    <condition>AML</condition>
    <condition>AML With Mutated NPM1</condition>
    <condition>Hematologic Malignancy</condition>
    <condition>KMT2Ar</condition>
    <condition>NPM1 Mutation</condition>
    <condition>MLL Rearrangement</condition>
    <condition>Leukemia</condition>
    <condition>Acute Myeloid Leukemia</condition>
    <condition>Leukemia, Myeloid</condition>
    <condition>Leukemia, Myeloid, Acute</condition>
    <condition>Acute Leukemia</condition>
    <condition>Neoplasms by Histologic Type</condition>
    <arm_group>
      <arm_group_label>Phase 1a</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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:&#xD;
  A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA&#xD;
  A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC)&#xD;
  A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib&#xD;
  B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA&#xD;
  B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Phase 1b</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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:&#xD;
  A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA&#xD;
  A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC)&#xD;
  A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib&#xD;
  B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA&#xD;
  B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ziftomenib</intervention_name>
      <description>Oral administration</description>
      <arm_group_label>Phase 1a</arm_group_label>
      <arm_group_label>Phase 1b</arm_group_label>
      <other_name>KO-539</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine</intervention_name>
      <description>Intravenous infusion</description>
      <arm_group_label>Phase 1a</arm_group_label>
      <arm_group_label>Phase 1b</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Idarubicin</intervention_name>
      <description>Intravenous infusion</description>
      <arm_group_label>Phase 1a</arm_group_label>
      <arm_group_label>Phase 1b</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cytarabine</intervention_name>
      <description>Intravenous Infusion</description>
      <arm_group_label>Phase 1a</arm_group_label>
      <arm_group_label>Phase 1b</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Gilteritinib</intervention_name>
      <description>Oral administration</description>
      <arm_group_label>Phase 1a</arm_group_label>
      <arm_group_label>Phase 1b</arm_group_label>
      <other_name>Xospata</other_name>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Granulocyte colony-stimulating factor</intervention_name>
      <description>Subcutaneous injection</description>
      <arm_group_label>Phase 1a</arm_group_label>
      <arm_group_label>Phase 1b</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria:&#xD;
  &#xD;
            -  Has been diagnosed with relapsed/refractory AML.&#xD;
  &#xD;
            -  Has a documented NPM1 mutation or KMT2A rearrangement.&#xD;
  &#xD;
            -  Has a documented FLT3 mutation (cohort A-3 only).&#xD;
  &#xD;
            -  Has an Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2.&#xD;
  &#xD;
            -  Has adequate hepatic and renal function as defined per protocol.&#xD;
  &#xD;
            -  Has an ejection fraction above a protocol defined limit.&#xD;
  &#xD;
            -  Participant, or legally authorized representative, must be able to understand and&#xD;
               provide written informed consent prior to the first screening procedure.&#xD;
  &#xD;
            -  Has agreed to use contraception as defined per protocol.&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
            -  Has a diagnosis of acute promyelocytic leukemia or blast chronic myeloid leukemia.&#xD;
  &#xD;
            -  Has clinically active central nervous system leukemia.&#xD;
  &#xD;
            -  Has an active and uncontrolled infection.&#xD;
  &#xD;
            -  Has a mean corrected QT interval (QTcF) &gt; 480ms.&#xD;
  &#xD;
            -  Has uncontrolled intercurrent illness, including, but not limited to protocol defined&#xD;
               cardiac disease.&#xD;
  &#xD;
            -  Has received radiation, chemotherapy, immunotherapy, or any other anticancer therapy&#xD;
               including investigational therapy &lt;14 days or within 5 drug half-lives prior to the&#xD;
               first dose of study intervention.&#xD;
  &#xD;
            -  Has had major surgery within 4 weeks prior to the first dose of study intervention.&#xD;
  &#xD;
            -  Has received a hematopoietic stem cell transplant (HSCT) and has not previously had&#xD;
               adequate recovery per protocol defined criteria.&#xD;
  &#xD;
            -  Has active graft-versus-host disease (GvHD) and or on immunosuppressive drugs for the&#xD;
               treatment of GvHD.&#xD;
  &#xD;
            -  Participant is pregnant or lactating.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Clinical Development</last_name>
      <role>Study Director</role>
      <affiliation>Kura Oncology</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Clinical Operations</last_name>
      <phone>617 588 3755</phone>
      <email>KO-MEN-008@kuraoncology.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Leukemia, Myeloid</mesh_term>
      <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
      <mesh_term>Hematologic Neoplasms</mesh_term>
      <mesh_term>Neoplasms by Histologic Type</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cytarabine</mesh_term>
      <mesh_term>Fludarabine</mesh_term>
      <mesh_term>Idarubicin</mesh_term>
      <mesh_term>Lenograstim</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06001788
  org study id: KO-MEN-008
  nct id: NCT06001788
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  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.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 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)
  description: Assessed by the NCI-CTCAE v5.0
  measure: 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
  description: Assessed by the NCI-CTCAE v5.0
  measure: 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
  description: Assessed by ELN 2022 criteria
  measure: 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
  description: Assessed by ELN 2022 criteria
  measure: Composite complete remission (CRc) rate
  time frame: Up to 12 months following discontinuation of treatment
  description: Assessed by ELN 2022 criteria
  measure: Morphologic leukemia-free state (MLFS) rate
  time frame: Up to 12 months following discontinuation of treatment
  description: Assessed by ELN 2022 criteria
  measure: OS
  time frame: Up to 12 months following discontinuation of treatment
  description: To assess overall survival
  measure: 6-month OS
  time frame: Up to 6 months following discontinuation of treatment
  description: To assess proportion of patients alive at 6 months
  measure: Median EFS
  time frame: Up to 12 months following discontinuation of treatment
  description: To assess median event free survival
  measure: 6-month EFS
  time frame: Up to 6 months following discontinuation of treatment
  description: To assess 6-month event free survival
  measure: DOR
  time frame: Up to 12 months following discontinuation of treatment
  description: To assess duration of remission
  measure: MRD assessment
  time frame: Up to 12 months following discontinuation of treatment
  description: To assess minimum residual disease in bone marrow
  measure: HSCT
  time frame: Up to 12 months following discontinuation of treatment
  description: To assess proportion of patients that undergo a hematopoietic stem-cell transplant
  measure: Transfusion independence
  time frame: Up to 12 months following discontinuation of treatment
  description: To assess transfusion independence
  measure: Ziftomenib Cmax
  time frame: Cycle 1 (Each cycle is 28 days)
  description: To assess the maximum plasma combination of ziftomenib and its metabolites
  measure: Ziftomenib Tmax
  time frame: Cycle 1 (Each cycle is 28 days)
  description: To assess the time to observed maximum plasma concentration of ziftomenib and its metabolites
  measure: Ziftomenib AUC(0-last)
  time frame: Cycle 1 (Each cycle is 28 days)
  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
  measure: Ziftomenib AUC(tau)
  time frame: Cycle 1 (Each cycle is 28 days)
  description: To assess the area under the plasma concentration-time-curve over a dosing interval for ziftomenib and its metabolites
  measure: Gilteritinib Cmax
  time frame: Cycle 1 (Each cycle is 28 days)
  description: To assess the maximum plasma combination of gilteritinib
  measure: Gilteritinib Tmax
  time frame: Cycle 1 (Each cycle is 28 days)
  description: To assess the time to observed maximum plasma concentration of gilteritinib
  measure: Gilteritinib AUC(0-last)
  time frame: Cycle 1 (Each cycle is 28 days)
  description: To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of gilteritinib
  measure: Gilteritinib AUC(tau)
  time frame: Cycle 1 (Each cycle is 28 days)
  description: To assess the area under the plasma concentration-time-curve over a dosing interval for gilteritinib
  arm group label: Phase 1a
  arm group type: Experimental
  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 group label: Phase 1b
  arm group type: Experimental
  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: Ziftomenib
  description: Oral administration
  arm group label: Phase 1a
  arm group label: Phase 1b
  other name: KO-539
  intervention type: Drug
  intervention name: Fludarabine
  description: Intravenous infusion
  arm group label: Phase 1a
  arm group label: Phase 1b
  intervention type: Drug
  intervention name: Idarubicin
  description: Intravenous infusion
  arm group label: Phase 1a
  arm group label: Phase 1b
  intervention type: Drug
  intervention name: Cytarabine
  description: Intravenous Infusion
  arm group label: Phase 1a
  arm group label: Phase 1b
  intervention type: Drug
  intervention name: Gilteritinib
  description: Oral administration
  arm group label: Phase 1a
  arm group label: Phase 1b
  other name: Xospata
  intervention type: Biological
  intervention name: Granulocyte colony-stimulating factor
  description: Subcutaneous injection
  arm group label: Phase 1a
  arm group label: Phase 1b
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Clinical Development
  role: Study Director
  affiliation: Kura Oncology
  last name: Clinical Operations
  phone: 617 588 3755
  email: KO-MEN-008@kuraoncology.com
  responsible party type: Sponsor
  mesh term: Leukemia
  mesh term: Leukemia, Myeloid
  mesh term: Leukemia, Myeloid, Acute
  mesh term: Hematologic Neoplasms
  mesh term: Neoplasms by Histologic Type
  mesh term: Cytarabine
  mesh term: Fludarabine
  mesh term: Idarubicin
  mesh term: Lenograstim
  sharing ipd: Undecided