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/NCT06034470</url>
    </required_header>
    <id_info>
      <org_study_id>RG1123378</org_study_id>
      <secondary_id>NCI-2023-03572</secondary_id>
      <secondary_id>RG1123378</secondary_id>
      <nct_id>NCT06034470</nct_id>
    </id_info>
    <brief_title>Combination Chemotherapy (FLAG-Ida) With Pivekimab Sunirine (PVEK [IMGN632]) for the Treatment of Newly Diagnosed Adverse Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms</brief_title>
    <official_title>Phase 1 Study of FLAG-Ida With Pivekimab Sunirine (PVEK [IMGN632]) for Adults With Newly Diagnosed Adverse-Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fred Hutchinson Cancer Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>ImmunoGen, Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Fred Hutchinson Cancer Center</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase I clinical trial finds the best dose of pivekimab sunirine (PVEK [IMGN632]) (PVEK)&#xD;
        when given together with fludarabine, high-dose cytarabine, granulocyte colony-stimulating&#xD;
        factor (G-CSF), and idarubicin, (FLAG-Ida) regimen and studies the effectiveness of this&#xD;
        combination therapy in treating patients with newly diagnosed adverse risk acute myeloid&#xD;
        leukemia (AML) and other high-grade myeloid neoplasms. PVEK is a monoclonal antibody linked&#xD;
        to a chemotherapy drug. PVEK is a form of targeted therapy because it attaches to specific&#xD;
        molecules (receptors) on the surface of cancer cells, known as CD123 receptors, and delivers&#xD;
        the chemotherapy drug to kill them. Chemotherapy drugs, such as idarubicin, fludarabine,&#xD;
        high-dose cytarabine work in different ways to stop the growth of cancer cells, either by&#xD;
        killing the cells, by stopping them from dividing, or by stopping them from spreading. G-CSF&#xD;
        helps the bone marrow make more white blood cells in patients with low white blood cell count&#xD;
        due to cancer treatment. Giving PVEK with FLAG-Ida regimen may kill more cancer cells than&#xD;
        the chemotherapy regimen alone.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        OUTLINE: This is a phase I, dose-escalation study of PVEK. Patients receive PVEK&#xD;
        intravenously (IV) plus G-CSF subcutaneously (SC), fludarabine IV, cytarabine IV, and&#xD;
        idarubicin IV on study.&#xD;
  &#xD;
        Patients undergo bone marrow aspiration and may undergo bone marrow biopsy and blood sample&#xD;
        collection throughout the trial. Patients also undergo echocardiography (ECHO) or multigated&#xD;
        acquisition (MUGA) scan during screening and as clinically indicated on trial.&#xD;
  &#xD;
        After completion of study treatment, patients are followed every 3 months for 2 years.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2027</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2026</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of dose-limiting toxicities during cycle 1</measure>
      <time_frame>During cycle 1 (each cycle is 42 days)</time_frame>
      <description>Dose-limiting toxicities (DLTs) for trial monitoring are defined as follows: a) Any Grade ≥4 organ toxicity; and b) prolonged severe myelosuppression, as defined by ANC &lt;500/µL and platelet count &lt;25,000/µL, for &gt;42 days after initiation (day 1) of FLAG-Ida chemotherapy in the absence of residual disease (assessed by morphology and flow cytometrically/molecularly/cytogenetically).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Incidence of adverse events</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Will be assessed by the NCI CTCAE v.5. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Measurable residual disease (MRD) rates</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Will be estimated within the limits of the study with pivekimab sunirine (PVEK) + fludarabine, high-dose cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida) across study cohorts. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>MRD status</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>MRD will be measured by multiparameter flow cytometry. All positive testing will be considered positive.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Relapse-free survival</measure>
      <time_frame>From the date of achievement of remission until the date of hematologic relapse or death from any cause, assessed up to 2 years</time_frame>
      <description>Will be assessed within the limits of the study by the relationship between MRD status after induction therapy and relapse risk/time to relapse. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>From day 1 of study treatment to the date of death from any cause, up to 2 years</time_frame>
      <description>Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Complete remission rates</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of cytopenias</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Will be evaluated by the impact of PVEK dosing regimens on the duration of cytopenias. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of patients receiving allogeneic hematopoietic cell transplantation</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Will be estimated within the limits of the study by the proportion of patients receiving allogeneic HCT in remission with PVEK + FLAG-Ida. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Acute Myeloid Leukemia</condition>
    <condition>Myeloid Neoplasm</condition>
    <arm_group>
      <arm_group_label>Treatment (PVEK, FLAG-Ida)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive PVEK IV plus G-CSF SC, fludarabine IV, cytarabine IV, and idarubicin IV on study. Patients undergo bone marrow aspiration and may undergo bone marrow biopsy and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA scan during screening and as clinically indicated on trial.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo blood sample collection</description>
      <arm_group_label>Treatment (PVEK, FLAG-Ida)</arm_group_label>
      <other_name>Biological Sample Collection</other_name>
      <other_name>Biospecimen Collected</other_name>
      <other_name>Specimen Collection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Bone Marrow Aspiration</intervention_name>
      <description>Undergo bone marrow aspirate</description>
      <arm_group_label>Treatment (PVEK, FLAG-Ida)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Bone Marrow Biopsy</intervention_name>
      <description>Undergo bone marrow biopsy</description>
      <arm_group_label>Treatment (PVEK, FLAG-Ida)</arm_group_label>
      <other_name>Biopsy of Bone Marrow</other_name>
      <other_name>Biopsy, Bone Marrow</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cytarabine</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Treatment (PVEK, FLAG-Ida)</arm_group_label>
      <other_name>.beta.-Cytosine arabinoside</other_name>
      <other_name>1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone</other_name>
      <other_name>1-.beta.-D-Arabinofuranosylcytosine</other_name>
      <other_name>1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone</other_name>
      <other_name>1-Beta-D-arabinofuranosylcytosine</other_name>
      <other_name>1.beta.-D-Arabinofuranosylcytosine</other_name>
      <other_name>2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-</other_name>
      <other_name>2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-</other_name>
      <other_name>Alexan</other_name>
      <other_name>Ara-C</other_name>
      <other_name>ARA-cell</other_name>
      <other_name>Arabine</other_name>
      <other_name>Arabinofuranosylcytosine</other_name>
      <other_name>Arabinosylcytosine</other_name>
      <other_name>Aracytidine</other_name>
      <other_name>Aracytin</other_name>
      <other_name>Aracytine</other_name>
      <other_name>Beta-Cytosine Arabinoside</other_name>
      <other_name>CHX-3311</other_name>
      <other_name>Cytarabinum</other_name>
      <other_name>Cytarbel</other_name>
      <other_name>Cytosar</other_name>
      <other_name>Cytosine Arabinoside</other_name>
      <other_name>Cytosine-.beta.-arabinoside</other_name>
      <other_name>Cytosine-beta-arabinoside</other_name>
      <other_name>Erpalfa</other_name>
      <other_name>Starasid</other_name>
      <other_name>Tarabine PFS</other_name>
      <other_name>U 19920</other_name>
      <other_name>U-19920</other_name>
      <other_name>Udicil</other_name>
      <other_name>WR-28453</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Echocardiography</intervention_name>
      <description>Undergo ECHO</description>
      <arm_group_label>Treatment (PVEK, FLAG-Ida)</arm_group_label>
      <other_name>EC</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Treatment (PVEK, FLAG-Ida)</arm_group_label>
      <other_name>Fluradosa</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Granulocyte Colony-Stimulating Factor</intervention_name>
      <description>Given SC</description>
      <arm_group_label>Treatment (PVEK, FLAG-Ida)</arm_group_label>
      <other_name>Colony Stimulating Factor 3</other_name>
      <other_name>Colony-Stimulating Factor (Granulocyte)</other_name>
      <other_name>Colony-Stimulating Factor 3</other_name>
      <other_name>CSF3</other_name>
      <other_name>G CSF</other_name>
      <other_name>G-CSF</other_name>
      <other_name>Granulocyte Colony Stimulating Factor</other_name>
      <other_name>Pluripoietin</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Idarubicin</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Treatment (PVEK, FLAG-Ida)</arm_group_label>
      <other_name>4-Demethoxydaunomycin</other_name>
      <other_name>4-Demethoxydaunorubicin</other_name>
      <other_name>4-DMDR</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Multigated Acquisition Scan</intervention_name>
      <description>Undergo MUGA scan</description>
      <arm_group_label>Treatment (PVEK, FLAG-Ida)</arm_group_label>
      <other_name>Blood Pool Scan</other_name>
      <other_name>Equilibrium Radionuclide Angiography</other_name>
      <other_name>Gated Blood Pool Imaging</other_name>
      <other_name>Gated Heart Pool Scan</other_name>
      <other_name>MUGA</other_name>
      <other_name>MUGA Scan</other_name>
      <other_name>Multi-Gated Acquisition Scan</other_name>
      <other_name>Radionuclide Ventriculogram Scan</other_name>
      <other_name>Radionuclide Ventriculography</other_name>
      <other_name>RNVG</other_name>
      <other_name>SYMA Scanning</other_name>
      <other_name>Synchronized Multigated Acquisition Scanning</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pivekimab Sunirine</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Treatment (PVEK, FLAG-Ida)</arm_group_label>
      <other_name>Anti-CD123 ADC IMGN632</other_name>
      <other_name>Antibody-drug Conjugate IMGN632</other_name>
      <other_name>CD123-targeted ADC IMGN632</other_name>
      <other_name>IMGN 632</other_name>
      <other_name>IMGN-632</other_name>
      <other_name>IMGN632</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age &gt;= 18 years&#xD;
  &#xD;
            -  Diagnosis of untreated AML other than acute promyelocytic leukemia (APL) with&#xD;
               t(15;17)(q22;q12) or variants according to the 5th edition of the World Health&#xD;
               Organization (WHO) classification of hematolymphoid tumors. Patients with&#xD;
               myelodysplastic, myeloproliferative, or myelodysplastic/myeloproliferative neoplasms&#xD;
               and ≥10% blasts in blood and/or bone marrow, are also eligible, as are patients with&#xD;
               mixed phenotype acute leukemia (MPAL). Outside diagnostic material is acceptable to&#xD;
               establish diagnosis; submission of peripheral blood specimen for flow cytometry&#xD;
               performed at the study institution should be considered. Diagnostic material must have&#xD;
               been submitted for cytogenetic and/or molecular testing as clinically appropriate&#xD;
  &#xD;
            -  Cytogenetically/molecularly adverse-risk disease (European LeukemiaNet [ELN] 2022&#xD;
               criteria)&#xD;
  &#xD;
            -  Expression of CD123 on immunophenotypically abnormal blasts, as assessed by local&#xD;
               multiparameter flow cytometry. Evaluation of CD123 expression via immunohistochemistry&#xD;
               is permissible, for example if flow cytometric assessment is not available&#xD;
  &#xD;
            -  Medically fit, as defined by treatment-related mortality (TRM) score =&lt; 13.1&#xD;
               calculated with simplified model&#xD;
  &#xD;
            -  The use of hydroxyurea prior to start of study therapy is allowed. Patients with&#xD;
               symptoms/signs of hyperleukocytosis, white blood cell (WBC) &gt; 100,000/uL or with&#xD;
               concern for other complications of high tumor burden (e.g. disseminated intravascular&#xD;
               coagulation) can be treated with leukapheresis prior to start of study therapy&#xD;
  &#xD;
            -  Patients may have received low-intensity treatment (e.g. azacitidine/decitabine,&#xD;
               lenalidomide, growth factors) for antecedent low-grade myeloid neoplasm (i.e. &lt; 10%&#xD;
               blasts in blood and bone marrow)&#xD;
  &#xD;
            -  Bilirubin =&lt; 1.5 x institutional upper limit of normal (IULN) unless elevation is&#xD;
               thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis&#xD;
  &#xD;
            -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =&lt; 3.0 x IULN&#xD;
               unless elevation is thought to be due to hepatic infiltration by AML&#xD;
  &#xD;
            -  Creatinine clearance ≥60 mL/min&#xD;
  &#xD;
            -  Left ventricular ejection fraction &gt;= 45%, assessed by multigated acquisition (MUGA)&#xD;
               scan or echocardiography or other appropriate diagnostic modality and no clinical&#xD;
               evidence of congestive heart failure&#xD;
  &#xD;
            -  Fertile male and female subjects must be willing to use an effective contraceptive&#xD;
               method before, during, and for at least 3 months after receiving the investigational&#xD;
               agent&#xD;
  &#xD;
            -  Provide written informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Diagnosis of blast phase chronic myeloid leukemia (CML)&#xD;
  &#xD;
            -  Patients with FLT3-mutated AML&#xD;
  &#xD;
            -  Concomitant illness associated with a likely survival of &lt; 1 year&#xD;
  &#xD;
            -  Active systemic fungal, bacterial, viral, or other infection, unless disease is under&#xD;
               treatment with antimicrobials, and/or controlled or stable (e.g. if specific,&#xD;
               effective therapy is not available/feasible or desired [e.g. known chronic viral&#xD;
               hepatitis, human immunodeficiency virus (HIV)]). Patient needs to be clinically stable&#xD;
               as defined as being afebrile and hemodynamically stable for 24 hours. Patients with&#xD;
               fever thought to be likely secondary to leukemia are eligible&#xD;
  &#xD;
            -  Known hypersensitivity to any study drug or prior &gt;= grade 3 hypersensitivity&#xD;
               reactions to monoclonal antibodies&#xD;
  &#xD;
            -  Confirmed or suspected pregnancy or active breast feeding&#xD;
  &#xD;
            -  Treatment with any other investigational anti-leukemia agent&#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>Mary-Elizabeth Percival</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Mary-Elizabeth Percival</last_name>
      <phone>206-606-1320</phone>
      <email>mperciva@uw.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Fred Hutch/University of Washington Cancer Consortium</name>
        <address>
          <city>Seattle</city>
          <state>Washington</state>
          <zip>98109</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Mary-Elizabeth Percival</last_name>
        <phone>206-606-1320</phone>
        <email>mperciva@uw.edu</email>
      </contact>
      <investigator>
        <last_name>Mary-Elizabeth Percival</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 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>Neoplasms</mesh_term>
      <mesh_term>Leukemia, Myeloid</mesh_term>
      <mesh_term>Leukemia, Myeloid, Acute</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>
      <mesh_term>Immunoconjugates</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</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/NCT06034470
  org study id: RG1123378
  secondary id: NCI-2023-03572
  secondary id: RG1123378
  nct id: NCT06034470
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This phase I clinical trial finds the best dose of pivekimab sunirine (PVEK [IMGN632]) (PVEK)
        when given together with fludarabine, high-dose cytarabine, granulocyte colony-stimulating
        factor (G-CSF), and idarubicin, (FLAG-Ida) regimen and studies the effectiveness of this
        combination therapy in treating patients with newly diagnosed adverse risk acute myeloid
        leukemia (AML) and other high-grade myeloid neoplasms. PVEK is a monoclonal antibody linked
        to a chemotherapy drug. PVEK is a form of targeted therapy because it attaches to specific
        molecules (receptors) on the surface of cancer cells, known as CD123 receptors, and delivers
        the chemotherapy drug to kill them. Chemotherapy drugs, such as idarubicin, fludarabine,
        high-dose cytarabine work in different ways to stop the growth of cancer cells, either by
        killing the cells, by stopping them from dividing, or by stopping them from spreading. G-CSF
        helps the bone marrow make more white blood cells in patients with low white blood cell count
        due to cancer treatment. Giving PVEK with FLAG-Ida regimen may kill more cancer cells than
        the chemotherapy regimen alone.
  OUTLINE: This is a phase I, dose-escalation study of PVEK. Patients receive PVEK
        intravenously (IV) plus G-CSF subcutaneously (SC), fludarabine IV, cytarabine IV, and
        idarubicin IV on study.
  
        Patients undergo bone marrow aspiration and may undergo bone marrow biopsy and blood sample
        collection throughout the trial. Patients also undergo echocardiography (ECHO) or multigated
        acquisition (MUGA) scan during screening and as clinically indicated on trial.
  
        After completion of study treatment, patients are followed every 3 months for 2 years.
  allocation: N/A
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of dose-limiting toxicities during cycle 1
  time frame: During cycle 1 (each cycle is 42 days)
  description: Dose-limiting toxicities (DLTs) for trial monitoring are defined as follows: a) Any Grade ≥4 organ toxicity; and b) prolonged severe myelosuppression, as defined by ANC <500/µL and platelet count <25,000/µL, for >42 days after initiation (day 1) of FLAG-Ida chemotherapy in the absence of residual disease (assessed by morphology and flow cytometrically/molecularly/cytogenetically).
  measure: Incidence of adverse events
  time frame: Up to 2 years
  description: Will be assessed by the NCI CTCAE v.5. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
  measure: Measurable residual disease (MRD) rates
  time frame: Up to 2 years
  description: Will be estimated within the limits of the study with pivekimab sunirine (PVEK) + fludarabine, high-dose cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida) across study cohorts. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
  measure: MRD status
  time frame: Up to 2 years
  description: MRD will be measured by multiparameter flow cytometry. All positive testing will be considered positive.
  measure: Relapse-free survival
  time frame: From the date of achievement of remission until the date of hematologic relapse or death from any cause, assessed up to 2 years
  description: Will be assessed within the limits of the study by the relationship between MRD status after induction therapy and relapse risk/time to relapse. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
  measure: Overall survival
  time frame: From day 1 of study treatment to the date of death from any cause, up to 2 years
  description: Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
  measure: Complete remission rates
  time frame: Up to 2 years
  description: Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
  measure: Duration of cytopenias
  time frame: Up to 2 years
  description: Will be evaluated by the impact of PVEK dosing regimens on the duration of cytopenias. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
  measure: Proportion of patients receiving allogeneic hematopoietic cell transplantation
  time frame: Up to 2 years
  description: Will be estimated within the limits of the study by the proportion of patients receiving allogeneic HCT in remission with PVEK + FLAG-Ida. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
  arm group label: Treatment (PVEK, FLAG-Ida)
  arm group type: Experimental
  description: Patients receive PVEK IV plus G-CSF SC, fludarabine IV, cytarabine IV, and idarubicin IV on study. Patients undergo bone marrow aspiration and may undergo bone marrow biopsy and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA scan during screening and as clinically indicated on trial.
  intervention type: Procedure
  intervention name: Biospecimen Collection
  description: Undergo blood sample collection
  arm group label: Treatment (PVEK, FLAG-Ida)
  other name: Biological Sample Collection
  other name: Biospecimen Collected
  other name: Specimen Collection
  intervention type: Procedure
  intervention name: Bone Marrow Aspiration
  description: Undergo bone marrow aspirate
  arm group label: Treatment (PVEK, FLAG-Ida)
  intervention type: Procedure
  intervention name: Bone Marrow Biopsy
  description: Undergo bone marrow biopsy
  arm group label: Treatment (PVEK, FLAG-Ida)
  other name: Biopsy of Bone Marrow
  other name: Biopsy, Bone Marrow
  intervention type: Drug
  intervention name: Cytarabine
  description: Given IV
  arm group label: Treatment (PVEK, FLAG-Ida)
  other name: .beta.-Cytosine arabinoside
  other name: 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  other name: 1-.beta.-D-Arabinofuranosylcytosine
  other name: 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  other name: 1-Beta-D-arabinofuranosylcytosine
  other name: 1.beta.-D-Arabinofuranosylcytosine
  other name: 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  other name: 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  other name: Alexan
  other name: Ara-C
  other name: ARA-cell
  other name: Arabine
  other name: Arabinofuranosylcytosine
  other name: Arabinosylcytosine
  other name: Aracytidine
  other name: Aracytin
  other name: Aracytine
  other name: Beta-Cytosine Arabinoside
  other name: CHX-3311
  other name: Cytarabinum
  other name: Cytarbel
  other name: Cytosar
  other name: Cytosine Arabinoside
  other name: Cytosine-.beta.-arabinoside
  other name: Cytosine-beta-arabinoside
  other name: Erpalfa
  other name: Starasid
  other name: Tarabine PFS
  other name: U 19920
  other name: U-19920
  other name: Udicil
  other name: WR-28453
  intervention type: Procedure
  intervention name: Echocardiography
  description: Undergo ECHO
  arm group label: Treatment (PVEK, FLAG-Ida)
  other name: EC
  intervention type: Drug
  intervention name: Fludarabine
  description: Given IV
  arm group label: Treatment (PVEK, FLAG-Ida)
  other name: Fluradosa
  intervention type: Drug
  intervention name: Granulocyte Colony-Stimulating Factor
  description: Given SC
  arm group label: Treatment (PVEK, FLAG-Ida)
  other name: Colony Stimulating Factor 3
  other name: Colony-Stimulating Factor (Granulocyte)
  other name: Colony-Stimulating Factor 3
  other name: CSF3
  other name: G CSF
  other name: G-CSF
  other name: Granulocyte Colony Stimulating Factor
  other name: Pluripoietin
  intervention type: Drug
  intervention name: Idarubicin
  description: Given IV
  arm group label: Treatment (PVEK, FLAG-Ida)
  other name: 4-Demethoxydaunomycin
  other name: 4-Demethoxydaunorubicin
  other name: 4-DMDR
  intervention type: Procedure
  intervention name: Multigated Acquisition Scan
  description: Undergo MUGA scan
  arm group label: Treatment (PVEK, FLAG-Ida)
  other name: Blood Pool Scan
  other name: Equilibrium Radionuclide Angiography
  other name: Gated Blood Pool Imaging
  other name: Gated Heart Pool Scan
  other name: MUGA
  other name: MUGA Scan
  other name: Multi-Gated Acquisition Scan
  other name: Radionuclide Ventriculogram Scan
  other name: Radionuclide Ventriculography
  other name: RNVG
  other name: SYMA Scanning
  other name: Synchronized Multigated Acquisition Scanning
  intervention type: Drug
  intervention name: Pivekimab Sunirine
  description: Given IV
  arm group label: Treatment (PVEK, FLAG-Ida)
  other name: Anti-CD123 ADC IMGN632
  other name: Antibody-drug Conjugate IMGN632
  other name: CD123-targeted ADC IMGN632
  other name: IMGN 632
  other name: IMGN-632
  other name: IMGN632
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Mary-Elizabeth Percival
  role: Principal Investigator
  affiliation: Fred Hutch/University of Washington Cancer Consortium
  last name: Mary-Elizabeth Percival
  phone: 206-606-1320
  email: mperciva@uw.edu
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Leukemia
  mesh term: Neoplasms
  mesh term: Leukemia, Myeloid
  mesh term: Leukemia, Myeloid, Acute
  mesh term: Cytarabine
  mesh term: Fludarabine
  mesh term: Idarubicin
  mesh term: Lenograstim
  mesh term: Immunoconjugates
  sharing ipd: No