<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/NCT02238925</url>
  </required_header>
  <id_info>
    <org_study_id>CLTR0310-206</org_study_id>
    <nct_id>NCT02238925</nct_id>
  </id_info>
  <brief_title>An Open Label Phase II Pharmacokinetic and Pharmacodynamic Assessment of the Potential for QTc Prolongation Following First Induction Treatment With CPX-351 (Cytarabine:Daunorubicin) Liposome Injection in Acute Leukemias and MDS Patients</brief_title>
  <official_title>An Open Label Phase II Pharmacokinetic and Pharmacodynamic Assessment of the Potential for QTc Prolongation Following First Induction Treatment With CPX-351 (Cytarabine:Daunorubicin) Liposome Injection in Acute Leukemias and MDS Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jazz Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jazz Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the effects of CPX-351 on cardiac repolarization,&#xD;
      assess plasma drug levels, asses serum copper levels, and assess drug levels in urine.&#xD;
&#xD;
      Efficacy and Safety will be assessed in all patients enrolled to the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is an open-label, single-arm, Phase II, PK and pharmacodynamic (PD) trial of&#xD;
      CPX-351 in patients with documented acute leukemia (AML or ALL) or MDS (IPSS score ≥ 1.5) and&#xD;
      suitable for treatment with intensive chemotherapy. Each patient will be screened for hepatic&#xD;
      impairment. Hepatic impairment will be assessed using the Child-Pugh system and only patients&#xD;
      with a Child-Pugh score &lt;7 points will be eligible for this study. Patients will receive up&#xD;
      to two inductions and four consolidation courses. Patients will be monitored for safety&#xD;
      (early deaths, adverse events, metabolic changes, etc.) and efficacy (response for AML, ALL,&#xD;
      and MDS) while on the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>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>Effect of CPX-351 on Cardiac Ventricular Repolarization (QTcF)</measure>
    <time_frame>21 days</time_frame>
    <description>Time-matched QTcF Changes From Baseline after the start of first infusion</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum Copper Levels Change From Baseline</measure>
    <time_frame>During 1st induction (up to 5 days)</time_frame>
    <description>Change from Baseline to Induction 1, Day 5</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete Response Rate</measure>
    <time_frame>Following 1st induction, following 2nd induction if applicable</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>Induction 1, Day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>Induction 1, Day 5</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Acute Myeloid Leukemia (AML)</condition>
  <condition>Acute Lymphoblastic Leukemia (ALL)</condition>
  <condition>Myelodysplastic Syndrome (MDS)</condition>
  <arm_group>
    <arm_group_label>CPX-351</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single Arm Study (Patients may receive up to 2 Inductions and 4 Consolidations):&#xD;
Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion.&#xD;
Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
Consolidations 1-4: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CPX-351</intervention_name>
    <arm_group_label>CPX-351</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to understand and voluntarily sign an informed consent form&#xD;
&#xD;
          -  Age ≥ 18 to ≤ 80 years at the time of signing the informed consent form&#xD;
&#xD;
          -  Life expectancy of at least 3 months&#xD;
&#xD;
          -  Pathological confirmation by bone marrow documenting the following:&#xD;
&#xD;
               -  Newly Diagnosed De novo AML according to WHO criteria except for Acute&#xD;
                  Promyelocytic Leukemia or patients with known favorable cytogenetics (see&#xD;
                  exclusion)&#xD;
&#xD;
               -  Newly Diagnosed Secondary AML age &lt;60 years and ≥76 to 80 years, defined as&#xD;
                  having a history of an antecedent hematologic disorder (myelodysplastic syndromes&#xD;
                  [MDS], myeloproliferative disease [MPD]or history of cytotoxic treatment for&#xD;
                  non-hematologic malignancy)&#xD;
&#xD;
               -  Patients with relapsed/refractory AML regardless of cytogenetic risk&#xD;
&#xD;
               -  Patients with relapsed/refractory ALL&#xD;
&#xD;
               -  Patients with MDS (IPSS score ≥ 1.5)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2&#xD;
&#xD;
          -  Able to adhere to the study visit schedule and other protocol requirements&#xD;
&#xD;
          -  Laboratory values fulfilling the following:&#xD;
&#xD;
               -  Serum Creatinine ≤ 2.0mg/dL&#xD;
&#xD;
               -  Hepatic function with a score of &lt; 7 points according to the Child-Pugh System&#xD;
&#xD;
               -  Serum alanine aminotransferase or aspartate aminotransferase &lt; 3 times the ULN.&#xD;
                  Note: If elevated liver enzymes are related to disease; contact medical monitor&#xD;
                  to discuss.&#xD;
&#xD;
          -  Cardiac ejection fraction ≥50% by ECHO or MUGA&#xD;
&#xD;
          -  Screening and Baseline QTcF (Fridericia's) less than 470 msec&#xD;
&#xD;
          -  Patients with second malignancies in remission may be eligible if there is clinical&#xD;
             evidence of disease stability for a period of greater than 6 months off cytotoxic&#xD;
             chemotherapy, documented by imaging, tumor marker studies, etc., at screening.&#xD;
             Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy,&#xD;
             are eligible.&#xD;
&#xD;
          -  All men and women must agree to practice effective contraception during the study&#xD;
             period if not otherwise documented to be infertile.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients eligible for participation in Study CLTR0310-301 (Phase III study of CPX-351&#xD;
             NCT01696084) or who have already participated in that study are not eligible for this&#xD;
             study.&#xD;
&#xD;
          -  Patients taking medications known to prolong the QTc interval directly or that&#xD;
             interact pharmacodynamically with medicines to prolong the QTc interval.&#xD;
&#xD;
          -  Rhythm abnormalities (other than sinus bradycardia with HR &lt; 50 bpm)&#xD;
&#xD;
          -  AV block (other than 1o AV Block with PR &gt; 200 msec)&#xD;
&#xD;
          -  Bundle branch block or QRS ≥ 120 msec&#xD;
&#xD;
          -  Abnormal T wave morphology (other than slight flattening)&#xD;
&#xD;
          -  Pathological U waves&#xD;
&#xD;
          -  Other QRS or T/U morphology preventing accurate determination of QT interval&#xD;
&#xD;
          -  Patients with unexplained syncope, history of or known risk factors for torsade des&#xD;
             pointes, including congenital long QT syndrome, or family history of LQTS.&#xD;
&#xD;
          -  Patients with history of and/or current evidence of myocardial impairment (e.g.&#xD;
             cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive&#xD;
             heart disease, and congestive heart failure) resulting in heart failure by New York&#xD;
             Heart Association Criteria (Class III or IV staging)&#xD;
&#xD;
          -  Newly diagnosed patients with Acute promyelocytic leukemia [t(15;17)] or favorable&#xD;
             cytogenetics, including t(8;21) or inv16&#xD;
&#xD;
          -  Clinical evidence of active CNS leukemic involvement&#xD;
&#xD;
          -  Chemotherapy or other investigational anticancer therapeutic drugs within 1 week prior&#xD;
             to study entry unless AEs have resolved and there is no interference with the&#xD;
             assessment of efficacy or safety; in the event of rapidly proliferative disease,&#xD;
             however, the use of hydroxyurea is permitted up to 12 hours before study entry.&#xD;
             Patients with prior bone marrow or stem cell transplant, considered for inclusion,&#xD;
             should be discussed with the medical monitor first.&#xD;
&#xD;
          -  Any serious medical condition or psychiatric illness that would prevent the patient&#xD;
             from providing informed consent&#xD;
&#xD;
          -  Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2&#xD;
             daunorubicin (or equivalent)&#xD;
&#xD;
          -  Active or uncontrolled infection. Patients with any infection receiving treatment&#xD;
             (antibiotic, antifungal or antiviral treatment) may be entered into the study but must&#xD;
             be afebrile and hemodynamically stable for ≥72 hrs. Patients with fevers believed to&#xD;
             be due to leukemia or MDS are eligible provided a thorough infection work-up is&#xD;
             negative and the patient is clinically and hemodynamically stable.&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Hypersensitivity to cytarabine, daunorubicin or liposomal products&#xD;
&#xD;
          -  History of Wilson's disease or other copper-related metabolic disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Franciscan Saint Francis Health</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <results_first_submitted>September 3, 2017</results_first_submitted>
  <results_first_submitted_qc>October 23, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">November 30, 2017</results_first_posted>
  <last_update_submitted>October 23, 2017</last_update_submitted>
  <last_update_submitted_qc>October 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Newly Diagnosed AML</keyword>
  <keyword>Secondary AML</keyword>
  <keyword>Relapsed/Refractory AML</keyword>
  <keyword>Relapsed/Refractory ALL</keyword>
  <keyword>MDS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>CPX-351</title>
          <description>Single Arm Study (Patients may receive up to 2 Inductions and up to 4 Consolidations):&#xD;
Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion.&#xD;
Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
Consolidations: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
CPX-351</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>CPX-351</title>
          <description>Single Arm Study (Patients may receive up to 2 Inductions and up to 4 Consolidations):&#xD;
Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion.&#xD;
Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
Consolidations: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
CPX-351</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="26"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65.2" spread="9.31"/>
                  </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="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Effect of CPX-351 on Cardiac Ventricular Repolarization (QTcF)</title>
        <description>Time-matched QTcF Changes From Baseline after the start of first infusion</description>
        <time_frame>21 days</time_frame>
        <population>All subjects who received any dose of study drug and had at least 1 time-matched change from baseline in ECG parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>CPX-351</title>
            <description>Single Arm Study (Patients may receive up to 2 Inductions and up to 4 Consolidations):&#xD;
Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion.&#xD;
Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
Consolidations: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
CPX-351</description>
          </group>
        </group_list>
        <measure>
          <title>Effect of CPX-351 on Cardiac Ventricular Repolarization (QTcF)</title>
          <description>Time-matched QTcF Changes From Baseline after the start of first infusion</description>
          <population>All subjects who received any dose of study drug and had at least 1 time-matched change from baseline in ECG parameters.</population>
          <units>msecs</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Time-point 0.75 h</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="15.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time-point 1.5 h</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="13.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time-point 2 h</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" spread="15.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time-point 3 h</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.3" spread="15.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time-point 4 h</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" spread="11.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time-point 6 h</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="11.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time-point 8 h</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="8.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time-point 12 h</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.3" spread="10.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time-point 24 h</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.2" spread="13.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Copper Levels Change From Baseline</title>
        <description>Change from Baseline to Induction 1, Day 5</description>
        <time_frame>During 1st induction (up to 5 days)</time_frame>
        <population>All subjects who received at least 1 dose of study drug and copper data were collected.</population>
        <group_list>
          <group group_id="O1">
            <title>CPX-351</title>
            <description>Single Arm Study (Patients may receive up to 2 Inductions and up to 4 Consolidations):&#xD;
Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion.&#xD;
Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
Consolidations: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
CPX-351</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Copper Levels Change From Baseline</title>
          <description>Change from Baseline to Induction 1, Day 5</description>
          <population>All subjects who received at least 1 dose of study drug and copper data were collected.</population>
          <units>μg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.95" spread="51.119"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Complete Response Rate</title>
        <time_frame>Following 1st induction, following 2nd induction if applicable</time_frame>
        <population>Efficacy population: All subjects who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>CPX-351</title>
            <description>Single Arm Study (Patients may receive up to 2 Inductions and up to 4 Consolidations):&#xD;
Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion.&#xD;
Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
Consolidations: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
CPX-351</description>
          </group>
        </group_list>
        <measure>
          <title>Complete Response Rate</title>
          <population>Efficacy population: All subjects who received at least 1 dose of study drug.</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="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax</title>
        <time_frame>Induction 1, Day 5</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CPX-351</title>
            <description>Single Arm Study (Patients may receive up to 2 Inductions and up to 4 Consolidations):&#xD;
Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion.&#xD;
Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
Consolidations: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
CPX-351</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax</title>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cytarabine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.00" lower_limit="0.75" upper_limit="8.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ara-U</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.00" lower_limit="5.78" upper_limit="8.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Daunorubicin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.00" lower_limit="0.75" upper_limit="6.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Daunorubicinol</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.00" lower_limit="1.50" upper_limit="48.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax</title>
        <time_frame>Induction 1, Day 5</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CPX-351</title>
            <description>Single Arm Study (Patients may receive up to 2 Inductions and up to 4 Consolidations):&#xD;
Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion.&#xD;
Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
Consolidations: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
CPX-351</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax</title>
          <units>ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cytarabine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62200" spread="20900"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ara-U</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1240" spread="252"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Daunorubicin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26000" spread="8510"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Daunorubicinol</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="147" spread="52.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were recorded from the start of infusion to the last day of the study period, whereas Serious Adverse Events were reported from the start of infusion until 30 days after completion of the study period.</time_frame>
      <desc>The Safety population included subjects receiving at least 1 dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>CPX-351</title>
          <description>Single Arm Study (Patients may receive up to 2 Inductions and up to 4 Consolidations):&#xD;
Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion.&#xD;
Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
Consolidations: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.&#xD;
CPX-351</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="26"/>
              </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="7" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Catheter Site Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Meningitis Bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pathogen Resistance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pulmonary Mycosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Ejection Fraction Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Acute Myeloid Leukamia Recurrent</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Respiratory Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </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="26" subjects_at_risk="26"/>
              </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="17" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharospasm</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Conjunctival Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dry Eye</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Vitreous Floaters</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Gingival Bleeding</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Lower</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Faecal Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Cheilitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal Reflux Disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Gingival Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Gait Disturbance</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Mucosal Inflammation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Nodule</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Clostridium Difficile Colitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Device Related Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Staphylococcal Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Excoriation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Human Rhinovirus Test Positive</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Viral Test Positive</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Weight Decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Weight Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Fluid Overload</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Fluid Retention</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Muscular Weakness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pain In Jaw</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Joint Swelling</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Stiffness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dizziness Postural</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Sinus Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Confusional State</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Sleep Disorder</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Chromaturia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Urinary Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Micturition Urgency</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Urinary Retention</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Oropharyngeal Pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pulmonary Oedema</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Rales</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Productive Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pulmonary Mass</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Upper-Airway Cough Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </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" subjects_affected="5" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Rash Erythematous</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Rash Papular</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Rash Pruritic</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Blood Blister</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Erythema Multiforme</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Purpura</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Rash Macular</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Skin Mass</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Associate Director, Clinical Trial Disclosure &amp; Transparency</name_or_title>
      <organization>Jazz Pharmaceuticals</organization>
      <email>tom.chmielewski@jazzpharma.com</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/NCT02238925
org study id: CLTR0310-206
nct id: NCT02238925
lead sponsor: 
has dmc: No
The purpose of this study is to assess the effects of CPX-351 on cardiac repolarization,
      assess plasma drug levels, asses serum copper levels, and assess drug levels in urine.

      Efficacy and Safety will be assessed in all patients enrolled to the study.
This study is an open-label, single-arm, Phase II, PK and pharmacodynamic (PD) trial of
      CPX-351 in patients with documented acute leukemia (AML or ALL) or MDS (IPSS score ≥ 1.5) and
      suitable for treatment with intensive chemotherapy. Each patient will be screened for hepatic
      impairment. Hepatic impairment will be assessed using the Child-Pugh system and only patients
      with a Child-Pugh score <7 points will be eligible for this study. Patients will receive up
      to two inductions and four consolidation courses. Patients will be monitored for safety
      (early deaths, adverse events, metabolic changes, etc.) and efficacy (response for AML, ALL,
      and MDS) while on the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Effect of CPX-351 on Cardiac Ventricular Repolarization (QTcF)
time frame: 21 days
description: Time-matched QTcF Changes From Baseline after the start of first infusion
measure: Serum Copper Levels Change From Baseline
time frame: During 1st induction (up to 5 days)
description: Change from Baseline to Induction 1, Day 5
measure: Complete Response Rate
time frame: Following 1st induction, following 2nd induction if applicable
measure: Tmax
time frame: Induction 1, Day 5
measure: Cmax
time frame: Induction 1, Day 5
arm group label: CPX-351
arm group type: Experimental
description: Single Arm Study (Patients may receive up to 2 Inductions and 4 Consolidations):
Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion.
Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion.
Consolidations 1-4: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.
intervention type: Drug
intervention name: CPX-351
arm group label: CPX-351
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid, Acute
mesh term: Preleukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Myelodysplastic Syndromes
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 