<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/NCT01729845</url>
  </required_header>
  <id_info>
    <org_study_id>2652.00</org_study_id>
    <secondary_id>NCI-2012-02224</secondary_id>
    <secondary_id>2652</secondary_id>
    <secondary_id>FH#2652</secondary_id>
    <secondary_id>2652.00</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <nct_id>NCT01729845</nct_id>
  </id_info>
  <brief_title>Decitabine Followed by Mitoxantrone Hydrochloride, Etoposide, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes</brief_title>
  <official_title>Mitoxantrone, Etoposide, and Cytarabine (MEC) Following Epigenetic Priming With Decitabine in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS): A Phase 1/2 Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fred Hutchinson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Fred Hutchinson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I/II trial studies the side effects and best dose of decitabine followed by&#xD;
      mitoxantrone hydrochloride, etoposide, and cytarabine and to see how well they work in&#xD;
      treating patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that has&#xD;
      returned after a period of improvement or does not respond to treatment. Drugs used in&#xD;
      chemotherapy, such as mitoxantrone hydrochloride, etoposide, cytarabine, and decitabine, work&#xD;
      in different ways to stop the growth of cancer cells, either by killing the cells, by&#xD;
      stopping them from dividing, or by stopping them from spreading. Giving more than one drug&#xD;
      (combination chemotherapy) may kill more cancer cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Estimate the maximum tolerated dose (MTD) of decitabine priming followed by sequential&#xD;
      mitoxantrone hydrochloride/etoposide/cytarabine (MEC) chemotherapy in adults with&#xD;
      relapsed/refractory acute myeloid leukemia (AML).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Determine, within the limits of a Phase 1/2 study, disease response and duration of&#xD;
      remission.&#xD;
&#xD;
      II. Identify biomarkers (e.g., deoxyribonucleic acid [DNA] methylation and/or gene expression&#xD;
      changes) associated with treatment responses.&#xD;
&#xD;
      OUTLINE: This is a phase I, dose-escalation study of decitabine followed by a phase II study.&#xD;
&#xD;
      Patients receive decitabine intravenously (IV) on days -9 to -5 (dose level 1), days -11 to&#xD;
      -5 (dose level 2), or days -14 to -5 (dose level 3).&#xD;
&#xD;
      INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV&#xD;
      on days 1-5, and cytarabine IV on days 1-5. Patients achieving complete response (CR) or CR&#xD;
      with incomplete platelet count recovery (CRp) may receive up to 2 courses of induction&#xD;
      therapy and up to 2 courses of consolidation therapy.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for up to 5&#xD;
      years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2012</start_date>
  <completion_date type="Actual">April 3, 2017</completion_date>
  <primary_completion_date type="Actual">August 25, 2016</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Most Efficacious and Tolerated Dosage of Decitabine (Period 1)</measure>
    <time_frame>through day 45</time_frame>
    <description>MTD (most tolerated dose) of decitabine, measured in number of dose limiting toxicities. MTD defined as the highest dose in which the incidence of dose limiting toxicity is &lt; 33%, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Remission Rate Including CR and CRp</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Complete remission (CR) and Complete remission with incomplete platelet recovery (CRp) categorized according to criteria recommended by International Working Groups:&#xD;
Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly; hemoglobin level at least 110 g/L, platelet count at least 100x10^9/L, and absolute neutrophil count at least 1.0 x10^9/L. In addition, all 3 blood counts should be no higher than the upper normal limit; Normal leukocyte differential; Bone marrow histologic remission defined as the presence of age-adjusted normocellularity, no more than 5% myeloblasts, and an osteomyelofibrosis grade no higher than 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Relapse-free Survival (for Patients Achieving CR or CRp)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Categorized according to criteria recommended by International Working Groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Survival measured as of day of last contact. Categorized according to criteria recommended by International Working Groups.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>Previously Treated Myelodysplastic Syndrome</condition>
  <condition>Recurrent Adult Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Treatment (decitabine, MEC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive decitabine IV on days -9 to -5 (dose level 1), days -11 to -5 (dose level 2), or days -14 to -5 (dose level 3).&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (decitabine, MEC)</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>Drug</intervention_type>
    <intervention_name>Decitabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (decitabine, MEC)</arm_group_label>
    <other_name>5-Aza-2'-deoxycytidine</other_name>
    <other_name>Dacogen</other_name>
    <other_name>Decitabine for Injection</other_name>
    <other_name>Deoxyazacytidine</other_name>
    <other_name>Dezocitidine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (decitabine, MEC)</arm_group_label>
    <other_name>Demethyl Epipodophyllotoxin Ethylidine Glucoside</other_name>
    <other_name>EPEG</other_name>
    <other_name>Lastet</other_name>
    <other_name>Toposar</other_name>
    <other_name>Vepesid</other_name>
    <other_name>VP 16-213</other_name>
    <other_name>VP-16</other_name>
    <other_name>VP-16-213</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (decitabine, MEC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mitoxantrone Hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (decitabine, MEC)</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>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Prior diagnosis of &quot;high-risk&quot; myelodysplastic syndrome (MDS) (&gt;= 10% blasts) or AML&#xD;
             other than acute promyelocytic leukemia (APL) with t(15;17) (q22;q12) or variants&#xD;
             according to the 2008 World Health Organization (WHO) classification; patients with&#xD;
             biphenotypic AML are eligible&#xD;
&#xD;
          -  Relapsed/persistent disease according to standard criteria requiring salvage therapy;&#xD;
             outside diagnostic material is acceptable as long as peripheral blood and/or bone&#xD;
             marrow slides are reviewed at the study institution; flow cytometric analysis of&#xD;
             peripheral blood and/or bone marrow should be performed according to institutional&#xD;
             practice guidelines&#xD;
&#xD;
          -  Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT)&#xD;
             are eligible if relapse occurs provided symptoms of graft-versus host disease are well&#xD;
             controlled with stable use of immunosuppressive agents&#xD;
&#xD;
          -  Treatment-related mortality (TRM) score =&lt; 9.2 as calculated with simplified model&#xD;
&#xD;
          -  Should be off any active therapy for AML with the exception of hydroxyurea for at&#xD;
             least 14 days prior to study registration unless patient has rapidly progressive&#xD;
             disease, and all grade 2-4 non-hematologic toxicities should have resolved&#xD;
&#xD;
          -  May have previously received monotherapy with demethylating agents for MDS or AML&#xD;
&#xD;
          -  May have previously received chemotherapy with MEC for MDS or AML&#xD;
&#xD;
          -  Patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) &gt;&#xD;
             100,000/uL can be treated with leukapheresis or may receive up to 2 doses of&#xD;
             cytarabine (up to 500 mg/m^2/dose) prior to enrollment&#xD;
&#xD;
          -  Bilirubin =&lt; 2 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;
             (assessed within 7 days prior to study day 1)&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 x IULN (assessed within 7 days prior to study day 1)&#xD;
&#xD;
          -  Left ventricular ejection fraction &gt;= 40%, assessed within 3 months prior to study day&#xD;
             1, e.g. by multi gated acquisition (MUGA) scan or echocardiography, or other&#xD;
             appropriate diagnostic modality and no clinical evidence of congestive heart failure;&#xD;
             if the patient had anthracycline-based therapy since the most recent cardiac&#xD;
             assessment, cardiac evaluation should be repeated if there is clinical or&#xD;
             radiographical suspicion of cardiac dysfunction, or if the previous cardiac assessment&#xD;
             was abnormal&#xD;
&#xD;
          -  Women of childbearing potential and men must agree to use adequate contraception&#xD;
&#xD;
          -  Provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refractory/relapsing myeloid blast crisis of chronic myeloid leukemia (CML), unless&#xD;
             patient is not 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 (e.g. if specific,&#xD;
             effective therapy is not available/feasible or desired [e.g. chronic viral hepatitis,&#xD;
             human immunodeficiency virus (HIV)]); patient needs to be clinically stable as defined&#xD;
             as being afebrile and hemodynamically stable for 24 hours; patients with fever thought&#xD;
             to be likely secondary to leukemia are eligible&#xD;
&#xD;
          -  Known hypersensitivity to any study drug&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Patients may not be receiving any other investigational agents&#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>Kadlec Clinic Hematology and Oncology</name>
      <address>
        <city>Kennewick</city>
        <state>Washington</state>
        <zip>99336</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EvergreenHealth Medical Center</name>
      <address>
        <city>Kirkland</city>
        <state>Washington</state>
        <zip>98033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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 2019</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <results_first_submitted>August 25, 2017</results_first_submitted>
  <results_first_submitted_qc>December 15, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">January 12, 2018</results_first_posted>
  <last_update_submitted>February 5, 2019</last_update_submitted>
  <last_update_submitted_qc>February 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fred Hutchinson Cancer Center</investigator_affiliation>
    <investigator_full_name>Anna Halpern</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytarabine</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Podophyllotoxin</mesh_term>
    <mesh_term>Mitoxantrone</mesh_term>
    <mesh_term>Etoposide phosphate</mesh_term>
    <mesh_term>Decitabine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Dose Level 1: 5-Days of Decitabine-MEC</title>
          <description>Patients receive decitabine IV days -9 to -5 (dose level 1).&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV&#xD;
Decitabine: Given IV&#xD;
Etoposide: Given IV&#xD;
Mitoxantrone Hydrochloride: Given IV</description>
        </group>
        <group group_id="P2">
          <title>Dose Level 2: 7-Days of Decitabine-MEC</title>
          <description>Patients receive decitabine IV days -11 to -5 (dose level 2).&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV&#xD;
Decitabine: Given IV&#xD;
Etoposide: Given IV&#xD;
Mitoxantrone Hydrochloride: Given IV</description>
        </group>
        <group group_id="P3">
          <title>Dose Level 3: 10-days of Decitabine-MEC</title>
          <description>Patients receive decitabine IV days -14 to -5 (dose level 3).&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Safety/Tolerability of Dec/MEC</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="34"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="34"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Efficacy of Dec/MEC</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Dose Level 1: 5-Days of Decitabine-MEC</title>
          <description>Patients receive decitabine IV days -9 to -5 (dose level 1).&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV&#xD;
Decitabine: Given IV&#xD;
Etoposide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Mitoxantrone Hydrochloride: Given IV</description>
        </group>
        <group group_id="B2">
          <title>Dose Level 2: 7-Days of Decitabine-MEC</title>
          <description>Patients receive decitabine IV days -11 to -5 (dose level 2).&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV&#xD;
Decitabine: Given IV&#xD;
Etoposide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Mitoxantrone Hydrochloride: Given IV</description>
        </group>
        <group group_id="B3">
          <title>Dose Level 3: 10-Days of Decitabine-MEC</title>
          <description>Patients receive decitabine IV days -14 to -5 (dose level 3).&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV&#xD;
Decitabine: Given IV&#xD;
Etoposide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Mitoxantrone Hydrochloride: Given IV</description>
        </group>
        <group group_id="B4">
          <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="6"/>
            <count group_id="B2" value="34"/>
            <count group_id="B3" value="12"/>
            <count group_id="B4" value="52"/>
          </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="54" lower_limit="54" upper_limit="66"/>
                    <measurement group_id="B2" value="55" lower_limit="19" upper_limit="70"/>
                    <measurement group_id="B3" value="57" lower_limit="32" upper_limit="72"/>
                    <measurement group_id="B4" value="55" lower_limit="19" upper_limit="72"/>
                  </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="1"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Most Efficacious and Tolerated Dosage of Decitabine (Period 1)</title>
        <description>MTD (most tolerated dose) of decitabine, measured in number of dose limiting toxicities. MTD defined as the highest dose in which the incidence of dose limiting toxicity is &lt; 33%, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)</description>
        <time_frame>through day 45</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 1: 5-Days of Decitabine-MEC</title>
            <description>Patients receive decitabine IV days -9 to -5 (dose level 1). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV&#xD;
Decitabine: Given IV&#xD;
Etoposide: Given IV&#xD;
Mitoxantrone Hydrochloride: Given IV</description>
          </group>
          <group group_id="O2">
            <title>Dose Level 2: 7-Days of Decitabine-MEC</title>
            <description>Patients receive decitabine IV days -11 to -5 (dose level 2). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV</description>
          </group>
          <group group_id="O3">
            <title>Dose Level 3: 10-Days of Decitabine-MEC</title>
            <description>Patients receive decitabine IV days -14 to -5 (dose level 1).&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Most Efficacious and Tolerated Dosage of Decitabine (Period 1)</title>
          <description>MTD (most tolerated dose) of decitabine, measured in number of dose limiting toxicities. MTD defined as the highest dose in which the incidence of dose limiting toxicity is &lt; 33%, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)</description>
          <units>Incidents</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Dose-limiting toxiticies</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Complete Remission</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Complete Remission, incomplete PLT recovery</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Complete Remission, incomplete blood count recover</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Morphologic leukemia-free state</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Resistant Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Death (among those who received MEC)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Remission Rate Including CR and CRp</title>
        <description>Complete remission (CR) and Complete remission with incomplete platelet recovery (CRp) categorized according to criteria recommended by International Working Groups:&#xD;
Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly; hemoglobin level at least 110 g/L, platelet count at least 100x10^9/L, and absolute neutrophil count at least 1.0 x10^9/L. In addition, all 3 blood counts should be no higher than the upper normal limit; Normal leukocyte differential; Bone marrow histologic remission defined as the presence of age-adjusted normocellularity, no more than 5% myeloblasts, and an osteomyelofibrosis grade no higher than 1.</description>
        <time_frame>Up to 5 years</time_frame>
        <population>Population includes all Dose Level 2 participants from both periods 1 and 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 2: 7-Days of Decitabine-MEC</title>
            <description>Patients receive decitabine IV days -11 to -5 (dose level 2). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Remission Rate Including CR and CRp</title>
          <description>Complete remission (CR) and Complete remission with incomplete platelet recovery (CRp) categorized according to criteria recommended by International Working Groups:&#xD;
Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly; hemoglobin level at least 110 g/L, platelet count at least 100x10^9/L, and absolute neutrophil count at least 1.0 x10^9/L. In addition, all 3 blood counts should be no higher than the upper normal limit; Normal leukocyte differential; Bone marrow histologic remission defined as the presence of age-adjusted normocellularity, no more than 5% myeloblasts, and an osteomyelofibrosis grade no higher than 1.</description>
          <population>Population includes all Dose Level 2 participants from both periods 1 and 2.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Relapse-free Survival (for Patients Achieving CR or CRp)</title>
        <description>Categorized according to criteria recommended by International Working Groups.</description>
        <time_frame>Up to 5 years</time_frame>
        <population>Population includes all Dose Level 2 participants, from both periods 1 and 2, who achieved CR or CRp</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 2: 7-Days of Decitabine-MEC</title>
            <description>Patients receive decitabine IV on days -11 to -5 (dose level 2)&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV&#xD;
Decitabine: Given IV&#xD;
Etoposide: Given IV&#xD;
Mitoxantrone Hydrochloride: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Relapse-free Survival (for Patients Achieving CR or CRp)</title>
          <description>Categorized according to criteria recommended by International Working Groups.</description>
          <population>Population includes all Dose Level 2 participants, from both periods 1 and 2, who achieved CR or CRp</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="150" lower_limit="20" upper_limit="1031"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Survival measured as of day of last contact. Categorized according to criteria recommended by International Working Groups.</description>
        <time_frame>Up to 5 years</time_frame>
        <population>Population includes all Dose Level 2 participants, from both periods 1 and 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 2: 7-Days of Decitabine-MEC</title>
            <description>Patients receive decitabine IV days -11 to -5 (dose level 2). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Survival measured as of day of last contact. Categorized according to criteria recommended by International Working Groups.</description>
          <population>Population includes all Dose Level 2 participants, from both periods 1 and 2.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="564" lower_limit="165" upper_limit="1239"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>Death's reported were not reportable Serous adverse events per protocol. They were expected, or not related to drug and/or described in the protocol and consent form.</desc>
      <group_list>
        <group group_id="E1">
          <title>Dose Level 1: 5-Days of Decitabine-MEC</title>
          <description>Patients receive decitabine IV days -9 to -5 (dose level 1).&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV</description>
        </group>
        <group group_id="E2">
          <title>Dose Level 2: 7-Days of Decitabine-MEC</title>
          <description>Patients receive decitabine IV days -11 to -5 (dose level 2).&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV</description>
        </group>
        <group group_id="E3">
          <title>Dose Level 3: 10-days of Decitabine-MEC</title>
          <description>Patients receive decitabine IV days -14 to -5 (dose level 3).&#xD;
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.&#xD;
Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Tropinemia/NSTEMI</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>C Diff</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Enteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Bacteremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fungal Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Respiratory Tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Soft Tissue Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Catheter Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Elevated Liver Function Tests</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Tumor Lysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </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" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Respitatory Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Mucositis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Elevated BR</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Maculopapular Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pulmonary Embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </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>Dr. Anna Halpern</name_or_title>
      <organization>Fred Hutch Cancer Research Center</organization>
      <phone>2066676233 ext 206</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/NCT01729845
org study id: 2652.00
secondary id: NCI-2012-02224
secondary id: 2652
secondary id: FH#2652
secondary id: 2652.00
secondary id: P30CA015704
nct id: NCT01729845
lead sponsor: 
collaborator: 
has dmc: No
This phase I/II trial studies the side effects and best dose of decitabine followed by
      mitoxantrone hydrochloride, etoposide, and cytarabine and to see how well they work in
      treating patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that has
      returned after a period of improvement or does not respond to treatment. Drugs used in
      chemotherapy, such as mitoxantrone hydrochloride, etoposide, cytarabine, and decitabine, 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. Giving more than one drug
      (combination chemotherapy) may kill more cancer cells.
PRIMARY OBJECTIVES:

      I. Estimate the maximum tolerated dose (MTD) of decitabine priming followed by sequential
      mitoxantrone hydrochloride/etoposide/cytarabine (MEC) chemotherapy in adults with
      relapsed/refractory acute myeloid leukemia (AML).

      SECONDARY OBJECTIVES:

      I. Determine, within the limits of a Phase 1/2 study, disease response and duration of
      remission.

      II. Identify biomarkers (e.g., deoxyribonucleic acid [DNA] methylation and/or gene expression
      changes) associated with treatment responses.

      OUTLINE: This is a phase I, dose-escalation study of decitabine followed by a phase II study.

      Patients receive decitabine intravenously (IV) on days -9 to -5 (dose level 1), days -11 to
      -5 (dose level 2), or days -14 to -5 (dose level 3).

      INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV
      on days 1-5, and cytarabine IV on days 1-5. Patients achieving complete response (CR) or CR
      with incomplete platelet count recovery (CRp) may receive up to 2 courses of induction
      therapy and up to 2 courses of consolidation therapy.

      After completion of study treatment, patients are followed up every 3 months for up to 5
      years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Most Efficacious and Tolerated Dosage of Decitabine (Period 1)
time frame: through day 45
description: MTD (most tolerated dose) of decitabine, measured in number of dose limiting toxicities. MTD defined as the highest dose in which the incidence of dose limiting toxicity is < 33%, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)
measure: Remission Rate Including CR and CRp
time frame: Up to 5 years
description: Complete remission (CR) and Complete remission with incomplete platelet recovery (CRp) categorized according to criteria recommended by International Working Groups:
Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly; hemoglobin level at least 110 g/L, platelet count at least 100x10^9/L, and absolute neutrophil count at least 1.0 x10^9/L. In addition, all 3 blood counts should be no higher than the upper normal limit; Normal leukocyte differential; Bone marrow histologic remission defined as the presence of age-adjusted normocellularity, no more than 5% myeloblasts, and an osteomyelofibrosis grade no higher than 1.
measure: Duration of Relapse-free Survival (for Patients Achieving CR or CRp)
time frame: Up to 5 years
description: Categorized according to criteria recommended by International Working Groups.
measure: Overall Survival
time frame: Up to 5 years
description: Survival measured as of day of last contact. Categorized according to criteria recommended by International Working Groups.
arm group label: Treatment (decitabine, MEC)
arm group type: Experimental
description: Patients receive decitabine IV on days -9 to -5 (dose level 1), days -11 to -5 (dose level 2), or days -14 to -5 (dose level 3).
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.
intervention type: Drug
intervention name: Cytarabine
description: Given IV
arm group label: Treatment (decitabine, MEC)
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: Drug
intervention name: Decitabine
description: Given IV
arm group label: Treatment (decitabine, MEC)
other name: 5-Aza-2'-deoxycytidine
other name: Dacogen
other name: Decitabine for Injection
other name: Deoxyazacytidine
other name: Dezocitidine
intervention type: Drug
intervention name: Etoposide
description: Given IV
arm group label: Treatment (decitabine, MEC)
other name: Demethyl Epipodophyllotoxin Ethylidine Glucoside
other name: EPEG
other name: Lastet
other name: Toposar
other name: Vepesid
other name: VP 16-213
other name: VP-16
other name: VP-16-213
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (decitabine, MEC)
intervention type: Drug
intervention name: Mitoxantrone Hydrochloride
description: Given IV
arm group label: Treatment (decitabine, MEC)
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
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: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Fred Hutchinson Cancer Center
investigator full name: Anna Halpern
investigator title: Principal Investigator
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
mesh term: Cytarabine
mesh term: Etoposide
mesh term: Podophyllotoxin
mesh term: Mitoxantrone
mesh term: Etoposide phosphate
mesh term: Decitabine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 