<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/NCT03012672</url>
  </required_header>
  <id_info>
    <org_study_id>9759</org_study_id>
    <secondary_id>NCI-2016-02051</secondary_id>
    <secondary_id>9759</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <secondary_id>RG9217016</secondary_id>
    <nct_id>NCT03012672</nct_id>
  </id_info>
  <brief_title>Higher or Lower Dose Cladribine, Cytarabine, and Mitoxantrone in Treating Medically Less Fit Patients With Newly Diagnosed Acute Myeloid Leukemia or Myeloid Neoplasm</brief_title>
  <official_title>Impact of Treatment Intensity on Survival, Quality of Life, and Resource Utilization in Medically Less Fit Adults With Acute Myeloid Leukemia and Analogous Myeloid Neoplasms: A Randomized Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized pilot trial studies how well higher or lower dose cladribine, cytarabine, and&#xD;
      mitoxantrone work in treating medically less fit patients with newly diagnosed acute myeloid&#xD;
      leukemia or myeloid neoplasm. Drugs used in chemotherapy, such as cladribine, cytarabine, and&#xD;
      mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing&#xD;
      the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet&#xD;
      known whether giving cladribine, cytarabine, and mitoxantrone at higher or lower dose may&#xD;
      work better in treating patients with newly diagnosed acute myeloid leukemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the feasibility of randomizing medically less fit adults with newly diagnosed&#xD;
      acute myeloid leukemia (AML) or analogous myeloid neoplasms to either intensive or&#xD;
      non-intensive induction and post remission chemotherapy.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the attitude of patients and physicians toward randomization and explore&#xD;
      reasons for treatment preference.&#xD;
&#xD;
      II. To evaluate whether the ability to assess fitness for intensive chemotherapy can be&#xD;
      improved by an augmented treatment-related mortality (TRM) score that includes additional&#xD;
      (co-morbidity) factors, and to compare the ability of physicians and the prediction&#xD;
      algorithm(s) to assess the likelihood of early death.&#xD;
&#xD;
      III. To compare, within the limits of a pilot study, response, duration of response, and&#xD;
      survival between patients receiving intensive and those receiving non-intensive chemotherapy.&#xD;
&#xD;
      IV. To describe the impact of treatment intensity on quality of life of patients undergoing&#xD;
      chemotherapy for newly diagnosed AML.&#xD;
&#xD;
      V. To describe the impact of treatment intensity on medical resource utilization and care&#xD;
      cost of patients undergoing chemotherapy for newly diagnosed AML.&#xD;
&#xD;
      OUTLINE: Patients agreeable to randomization are randomized to 1 of 2 treatment arms.&#xD;
      Patients not agreeable to randomization receive treatment based on their preference.&#xD;
&#xD;
      ARM I (HIGHER-DOSE):&#xD;
&#xD;
      INDUCTION: Patients receive granulocyte colony-stimulating factor (G-CSF) subcutaneously (SC)&#xD;
      on days 0-5, higher dose cladribine intravenously (IV) over 2 hours on days 1-5, higher dose&#xD;
      cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on&#xD;
      days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      CONSOLIDATION: Patients who achieve complete response (CR)/CR with incomplete count recovery&#xD;
      (CRi) with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in&#xD;
      Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      ARM II (LOWER-DOSE):&#xD;
&#xD;
      INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on&#xD;
      days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV&#xD;
      over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      CONSOLIDATION: Patients who achieve complete response (CR)/CR with incomplete count recovery&#xD;
      (CRi) with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in&#xD;
      Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up periodically for 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 30, 2016</start_date>
  <completion_date type="Actual">February 26, 2021</completion_date>
  <primary_completion_date type="Actual">December 10, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility Defined as Proportion of Patients Willing to be Randomized to Either Intensive or Non-intensive Induction and Post Remission Chemotherapy</measure>
    <time_frame>At end of enrollment</time_frame>
    <description>Randomizing patients to either intensive or non-intensive induction and post remission chemotherapy will be considered feasible if the true proportion of patients willing to be randomized is 60% or higher.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Event-free Survival</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Medical Complications</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Information on medical complications (e.g. need for intensive care unit (ICU) level care, length of ICU stay, neutropenic fever, documented infections, bleeding, reasons for hospitalization) will be collected from the medical records from the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA).</description>
  </other_outcome>
  <other_outcome>
    <measure>Medical Resource Utilization</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Information on use of medical resources (e.g. platelet transfusions; days of IV antimicrobial therapy, total hospital length of stay) will be collected from the medical records from the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA).</description>
  </other_outcome>
  <other_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be assessed for all patients. Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Quality of Life as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Will be measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. Exploratory, descriptive, and observational methods will be used.</description>
  </other_outcome>
  <other_outcome>
    <measure>Relapse-free Survival</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Response</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The differences in anti-leukemic efficacy between patients treated with lower-intensity chemotherapy and those treated with higher-intensity chemotherapy will be estimated. Exploratory, descriptive, and observational methods will be used.</description>
  </other_outcome>
  <other_outcome>
    <measure>Fitness for Intensive Chemotherapy as Measured by a Treatment-related Mortality (TRM) Score That Includes Additional Co-morbidity Factors</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>The ability of physicians and the prediction algorithm(s) to assess the likelihood of early death will be compared.</description>
  </other_outcome>
  <other_outcome>
    <measure>Duration of Response</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be evaluated.</description>
  </other_outcome>
  <other_outcome>
    <measure>Care Costs</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The costs associated with inpatient and outpatient management will be calculated using electronic billing information from the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA). Costs will be converted from charges using departmental cost-to-charge ratios. Descriptive information identifying major cost drivers and total/subset costs per phase of treatment will be reported.</description>
  </other_outcome>
  <other_outcome>
    <measure>Attitude of Patients Toward Randomization</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Will be determined by a patient preference survey. Exploratory, descriptive, and observational methods will be used.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Acute Leukemia of Ambiguous Lineage</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Myeloid Neoplasm</condition>
  <arm_group>
    <arm_group_label>Arm I (higher-dose)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>INDUCTION: Patients receive G-CSF SC on days 0-5, higher dose cladribine IV over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.&#xD;
CONSOLIDATION: Patients who achieve CR/CRi with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (lower-dose)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
CONSOLIDATION: Patients who achieve CR/CRi with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cladribine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (higher-dose)</arm_group_label>
    <arm_group_label>Arm II (lower-dose)</arm_group_label>
    <other_name>2-CdA</other_name>
    <other_name>2CDA</other_name>
    <other_name>CdA</other_name>
    <other_name>Cladribina</other_name>
    <other_name>Leustat</other_name>
    <other_name>Leustatin</other_name>
    <other_name>Leustatine</other_name>
    <other_name>RWJ-26251</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (higher-dose)</arm_group_label>
    <arm_group_label>Arm II (lower-dose)</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>Cytosar-U</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>Biological</intervention_type>
    <intervention_name>Granulocyte Colony-Stimulating Factor</intervention_name>
    <description>Given SC</description>
    <arm_group_label>Arm I (higher-dose)</arm_group_label>
    <arm_group_label>Arm II (lower-dose)</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>Mitoxantrone Hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (higher-dose)</arm_group_label>
    <arm_group_label>Arm II (lower-dose)</arm_group_label>
    <other_name>CL 232315</other_name>
    <other_name>DHAD</other_name>
    <other_name>DHAQ</other_name>
    <other_name>Dihydroxyanthracenedione Dihydrochloride</other_name>
    <other_name>Mitoxantrone Dihydrochloride</other_name>
    <other_name>Mitoxantroni Hydrochloridum</other_name>
    <other_name>Mitozantrone Hydrochloride</other_name>
    <other_name>Mitroxone</other_name>
    <other_name>Neotalem</other_name>
    <other_name>Novantrone</other_name>
    <other_name>Onkotrone</other_name>
    <other_name>Pralifan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm I (higher-dose)</arm_group_label>
    <arm_group_label>Arm II (lower-dose)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm I (higher-dose)</arm_group_label>
    <arm_group_label>Arm II (lower-dose)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of untreated &quot;high-grade&quot; myeloid neoplasm (&gt;= 10% myeloid blasts by&#xD;
             morphology in bone marrow and/or peripheral blood) or AML other than acute&#xD;
             promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016&#xD;
             World Health Organization (WHO) classification; patients with acute leukemias of&#xD;
             ambiguous lineage are eligible; outside diagnostic material is acceptable as long as&#xD;
             peripheral blood and/or bone marrow slides are reviewed at the study institution and&#xD;
             cytogenetic/molecular information is available&#xD;
&#xD;
          -  Treatment-related mortality (TRM) score &gt;= 13.1 as calculated with simplified model&#xD;
&#xD;
          -  The use of hydroxyurea before enrollment is permitted; hydroxyurea should be&#xD;
             discontinued prior to start of study treatment. Patients with symptoms/signs of&#xD;
             leukostasis, white blood cell (WBC) &gt; 100,000/uL, or acute symptoms felt related to&#xD;
             their high-grade myeloid neoplasm can be treated with leukapheresis or may receive up&#xD;
             to 1 dose of cytarabine (up to 500 mg/m^2) anytime prior to study day 1&#xD;
&#xD;
          -  Patients may have received treatment (e.g. azacitidine/decitabine, lenalidomide,&#xD;
             growth factors) for antecedent low-grade myeloid neoplasm&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) &gt;= 45%, assessed within 3 months prior to&#xD;
             registration, e.g. by multigated acquisition (MUGA) scan or echocardiography, or other&#xD;
             appropriate diagnostic modality&#xD;
&#xD;
          -  Women of childbearing potential and men must agree to use adequate contraception&#xD;
             beginning at the signing of the consent until at least 4 weeks after the last dose of&#xD;
             study drug&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not&#xD;
             considered candidate for tyrosine kinase inhibitor treatment&#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 anti-microbials and/or controlled or stable; patients with fever&#xD;
             thought to be likely secondary to leukemia are eligible; known hypersensitivity to any&#xD;
             study drug&#xD;
&#xD;
          -  Known hypersensitivity to any study drug used in this trial&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Concurrent treatment with any other 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>Anna Halpern</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <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>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <results_first_submitted>September 30, 2021</results_first_submitted>
  <results_first_submitted_qc>September 30, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 1, 2021</results_first_posted>
  <last_update_submitted>February 23, 2022</last_update_submitted>
  <last_update_submitted_qc>February 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Washington</investigator_affiliation>
    <investigator_full_name>Anna Halpern</investigator_full_name>
    <investigator_title>Assistant Professor, Division of Hematology</investigator_title>
  </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>2-chloro-3'-deoxyadenosine</mesh_term>
    <mesh_term>Mitoxantrone</mesh_term>
    <mesh_term>Cladribine</mesh_term>
    <mesh_term>Lenograstim</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 20, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/72/NCT03012672/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm I (Higher-dose)</title>
          <description>INDUCTION: Patients receive G-CSF SC on days 0-5, higher dose cladribine IV over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.&#xD;
CONSOLIDATION: Patients who achieve CR/CRi with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="P2">
          <title>Arm II (Lower-dose)</title>
          <description>INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
CONSOLIDATION: Patients who achieve CR/CRi with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>ARM I (HIGHER-DOSE)</title>
          <description>ARM I (HIGHER-DOSE):&#xD;
INDUCTION: Patients receive granulocyte colony-stimulating factor (G-CSF) subcutaneously (SC) on days 0-5, higher dose cladribine intravenously (IV) over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.&#xD;
CONSOLIDATION: Patients who achieve complete response (CR)/CR with incomplete count recovery (CRi) with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="B2">
          <title>ARM II (LOWER-DOSE)</title>
          <description>ARM II (LOWER-DOSE):&#xD;
INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
CONSOLIDATION: Patients who achieve complete response (CR)/CR with incomplete count recovery (CRi) with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="50"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="71.5" lower_limit="42" upper_limit="82"/>
                    <measurement group_id="B2" value="72" lower_limit="44" upper_limit="89"/>
                    <measurement group_id="B3" value="72" lower_limit="42" upper_limit="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Secondary Disease</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>De Novo</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Secondary</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ELN Risk Category</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Favorable</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Intermediate</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Adverse</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Classifiable</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Defined as Proportion of Patients Willing to be Randomized to Either Intensive or Non-intensive Induction and Post Remission Chemotherapy</title>
        <description>Randomizing patients to either intensive or non-intensive induction and post remission chemotherapy will be considered feasible if the true proportion of patients willing to be randomized is 60% or higher.</description>
        <time_frame>At end of enrollment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Patients Enrolled</title>
            <description>Total number of patients enrolled</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Defined as Proportion of Patients Willing to be Randomized to Either Intensive or Non-intensive Induction and Post Remission Chemotherapy</title>
          <description>Randomizing patients to either intensive or non-intensive induction and post remission chemotherapy will be considered feasible if the true proportion of patients willing to be randomized is 60% or higher.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Patients/physician pairs agreed to be randomized</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Patients/physician pairs not agreed to be randomized</title>
                  <measurement_list>
                    <measurement group_id="O1" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Event-free Survival</title>
        <description>Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Medical Complications</title>
        <description>Information on medical complications (e.g. need for intensive care unit (ICU) level care, length of ICU stay, neutropenic fever, documented infections, bleeding, reasons for hospitalization) will be collected from the medical records from the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA).</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Medical Resource Utilization</title>
        <description>Information on use of medical resources (e.g. platelet transfusions; days of IV antimicrobial therapy, total hospital length of stay) will be collected from the medical records from the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA).</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Overall Survival</title>
        <description>Will be assessed for all patients. Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Quality of Life as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30</title>
        <description>Will be measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. Exploratory, descriptive, and observational methods will be used.</description>
        <time_frame>Up to 12 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Relapse-free Survival</title>
        <description>Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Response</title>
        <description>The differences in anti-leukemic efficacy between patients treated with lower-intensity chemotherapy and those treated with higher-intensity chemotherapy will be estimated. Exploratory, descriptive, and observational methods will be used.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Fitness for Intensive Chemotherapy as Measured by a Treatment-related Mortality (TRM) Score That Includes Additional Co-morbidity Factors</title>
        <description>The ability of physicians and the prediction algorithm(s) to assess the likelihood of early death will be compared.</description>
        <time_frame>Up to 12 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Duration of Response</title>
        <description>Will be evaluated.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Care Costs</title>
        <description>The costs associated with inpatient and outpatient management will be calculated using electronic billing information from the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA). Costs will be converted from charges using departmental cost-to-charge ratios. Descriptive information identifying major cost drivers and total/subset costs per phase of treatment will be reported.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Attitude of Patients Toward Randomization</title>
        <description>Will be determined by a patient preference survey. Exploratory, descriptive, and observational methods will be used.</description>
        <time_frame>Up to 12 months</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs were collected for the duration that each patient remained on protocol. If a subject decided to terminate the study early AEs continued to be collected for up to 4 weeks after the treatment was given or until they started a new anti-leukemia therapy, whichever occurred first.</time_frame>
      <desc>Only grade ≥3 adverse events other than hematologic toxicities were recorded, graded, and reported as appropriate.</desc>
      <group_list>
        <group group_id="E1">
          <title>ARM I (HIGHER-DOSE):</title>
          <description>ARM I (HIGHER-DOSE):&#xD;
INDUCTION: Patients receive granulocyte colony-stimulating factor (G-CSF) subcutaneously (SC) on days 0-5, higher dose cladribine intravenously (IV) over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.&#xD;
CONSOLIDATION: Patients who achieve complete response (CR)/CR with incomplete count recovery (CRi) with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="E2">
          <title>ARM II (LOWER-DOSE):</title>
          <description>ARM II (LOWER-DOSE):&#xD;
INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
CONSOLIDATION: Patients who achieve complete response (CR)/CR with incomplete count recovery (CRi) with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE Version 5.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Intracranial Hemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E2" events="13" subjects_affected="7" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Right Ventricular Dysfunction</sub_title>
                <description>Type II NSTEMI</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pericardial Effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colonic Pseudo-Obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Multi-organ failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Generalized Edema</sub_title>
                <description>Anasarca</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vascular Access Complication</sub_title>
                <description>Non-occlusive R axillary DVT and superficial thrombophlebitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE Version 5.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="20"/>
                <counts group_id="E2" events="21" subjects_affected="15" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Tumor Lysis Syndrome</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Edema Limbs, Volume Overload</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Cardiac Troponin I Increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Paroxysmal Atrial Tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pericardial Effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pericarditis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Restrictive Cardiomyopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Blood Clot, Right Ear</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Optic Nerve Disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Generalized Edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteremia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Catheter Related Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Soft Tissue Infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Mucositis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>AST/ALT Elevation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Blood Bilirubin Increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Ejection Fraction Decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Alkalosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Bronchopulmonary Hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pulmonary Edema</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>COPD Exacerbation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash Maculo-Papular</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="20"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Anna Halpern, MD</name_or_title>
      <organization>University of Washington</organization>
      <phone>206-606-1978</phone>
      <email>halpern2@uw.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


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/NCT03012672
org study id: 9759
secondary id: NCI-2016-02051
secondary id: 9759
secondary id: P30CA015704
secondary id: RG9217016
nct id: NCT03012672
lead sponsor: 
collaborator: 
has dmc: Yes
This randomized pilot trial studies how well higher or lower dose cladribine, cytarabine, and
      mitoxantrone work in treating medically less fit patients with newly diagnosed acute myeloid
      leukemia or myeloid neoplasm. Drugs used in chemotherapy, such as cladribine, cytarabine, and
      mitoxantrone, 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. It is not yet
      known whether giving cladribine, cytarabine, and mitoxantrone at higher or lower dose may
      work better in treating patients with newly diagnosed acute myeloid leukemia.
PRIMARY OBJECTIVES:

      I. To evaluate the feasibility of randomizing medically less fit adults with newly diagnosed
      acute myeloid leukemia (AML) or analogous myeloid neoplasms to either intensive or
      non-intensive induction and post remission chemotherapy.

      EXPLORATORY OBJECTIVES:

      I. To evaluate the attitude of patients and physicians toward randomization and explore
      reasons for treatment preference.

      II. To evaluate whether the ability to assess fitness for intensive chemotherapy can be
      improved by an augmented treatment-related mortality (TRM) score that includes additional
      (co-morbidity) factors, and to compare the ability of physicians and the prediction
      algorithm(s) to assess the likelihood of early death.

      III. To compare, within the limits of a pilot study, response, duration of response, and
      survival between patients receiving intensive and those receiving non-intensive chemotherapy.

      IV. To describe the impact of treatment intensity on quality of life of patients undergoing
      chemotherapy for newly diagnosed AML.

      V. To describe the impact of treatment intensity on medical resource utilization and care
      cost of patients undergoing chemotherapy for newly diagnosed AML.

      OUTLINE: Patients agreeable to randomization are randomized to 1 of 2 treatment arms.
      Patients not agreeable to randomization receive treatment based on their preference.

      ARM I (HIGHER-DOSE):

      INDUCTION: Patients receive granulocyte colony-stimulating factor (G-CSF) subcutaneously (SC)
      on days 0-5, higher dose cladribine intravenously (IV) over 2 hours on days 1-5, higher dose
      cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on
      days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease
      progression or unacceptable toxicity.

      CONSOLIDATION: Patients who achieve complete response (CR)/CR with incomplete count recovery
      (CRi) with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in
      Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease
      progression or unacceptable toxicity.

      ARM II (LOWER-DOSE):

      INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on
      days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV
      over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the
      absence of disease progression or unacceptable toxicity.

      CONSOLIDATION: Patients who achieve complete response (CR)/CR with incomplete count recovery
      (CRi) with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in
      Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up periodically for 5 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility Defined as Proportion of Patients Willing to be Randomized to Either Intensive or Non-intensive Induction and Post Remission Chemotherapy
time frame: At end of enrollment
description: Randomizing patients to either intensive or non-intensive induction and post remission chemotherapy will be considered feasible if the true proportion of patients willing to be randomized is 60% or higher.
measure: Event-free Survival
time frame: Up to 5 years
description: Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups.
measure: Medical Complications
time frame: Up to 5 years
description: Information on medical complications (e.g. need for intensive care unit (ICU) level care, length of ICU stay, neutropenic fever, documented infections, bleeding, reasons for hospitalization) will be collected from the medical records from the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA).
measure: Medical Resource Utilization
time frame: Up to 5 years
description: Information on use of medical resources (e.g. platelet transfusions; days of IV antimicrobial therapy, total hospital length of stay) will be collected from the medical records from the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA).
measure: Overall Survival
time frame: Up to 5 years
description: Will be assessed for all patients. Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups.
measure: Quality of Life as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30
time frame: Up to 12 months
description: Will be measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. Exploratory, descriptive, and observational methods will be used.
measure: Relapse-free Survival
time frame: Up to 5 years
description: Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups.
measure: Response
time frame: Up to 5 years
description: The differences in anti-leukemic efficacy between patients treated with lower-intensity chemotherapy and those treated with higher-intensity chemotherapy will be estimated. Exploratory, descriptive, and observational methods will be used.
measure: Fitness for Intensive Chemotherapy as Measured by a Treatment-related Mortality (TRM) Score That Includes Additional Co-morbidity Factors
time frame: Up to 12 months
description: The ability of physicians and the prediction algorithm(s) to assess the likelihood of early death will be compared.
measure: Duration of Response
time frame: Up to 5 years
description: Will be evaluated.
measure: Care Costs
time frame: Up to 5 years
description: The costs associated with inpatient and outpatient management will be calculated using electronic billing information from the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA). Costs will be converted from charges using departmental cost-to-charge ratios. Descriptive information identifying major cost drivers and total/subset costs per phase of treatment will be reported.
measure: Attitude of Patients Toward Randomization
time frame: Up to 12 months
description: Will be determined by a patient preference survey. Exploratory, descriptive, and observational methods will be used.
arm group label: Arm I (higher-dose)
arm group type: Experimental
description: INDUCTION: Patients receive G-CSF SC on days 0-5, higher dose cladribine IV over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
arm group label: Arm II (lower-dose)
arm group type: Experimental
description: INDUCTION: Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Cladribine
description: Given IV
arm group label: Arm I (higher-dose)
arm group label: Arm II (lower-dose)
other name: 2-CdA
other name: 2CDA
other name: CdA
other name: Cladribina
other name: Leustat
other name: Leustatin
other name: Leustatine
other name: RWJ-26251
intervention type: Drug
intervention name: Cytarabine
description: Given IV
arm group label: Arm I (higher-dose)
arm group label: Arm II (lower-dose)
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: Cytosar-U
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: Biological
intervention name: Granulocyte Colony-Stimulating Factor
description: Given SC
arm group label: Arm I (higher-dose)
arm group label: Arm II (lower-dose)
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: Mitoxantrone Hydrochloride
description: Given IV
arm group label: Arm I (higher-dose)
arm group label: Arm II (lower-dose)
other name: CL 232315
other name: DHAD
other name: DHAQ
other name: Dihydroxyanthracenedione Dihydrochloride
other name: Mitoxantrone Dihydrochloride
other name: Mitoxantroni Hydrochloridum
other name: Mitozantrone Hydrochloride
other name: Mitroxone
other name: Neotalem
other name: Novantrone
other name: Onkotrone
other name: Pralifan
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Arm I (higher-dose)
arm group label: Arm II (lower-dose)
other name: Quality of Life Assessment
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Arm I (higher-dose)
arm group label: Arm II (lower-dose)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anna Halpern
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Washington
investigator full name: Anna Halpern
investigator title: Assistant Professor, Division of Hematology
mesh term: Leukemia
mesh term: Neoplasms
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Cytarabine
mesh term: 2-chloro-3'-deoxyadenosine
mesh term: Mitoxantrone
mesh term: Cladribine
mesh term: Lenograstim
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 