<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/NCT02186834</url>
  </required_header>
  <id_info>
    <org_study_id>MCC-17814</org_study_id>
    <nct_id>NCT02186834</nct_id>
  </id_info>
  <brief_title>Selinexor (KPT-330) and Liposomal Doxorubicin For Relapsed and Refractory Multiple Myeloma</brief_title>
  <official_title>Investigator-Initiated Phase I/II Clinical Trial of Selinexor (KPT-330) and Liposomal Doxorubicin for Relapsed and Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>H. Lee Moffitt Cancer Center and Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Karyopharm Therapeutics Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>H. Lee Moffitt Cancer Center and Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to determine the recommended doses of selinexor in&#xD;
      combination with liposomal doxorubicin and dexamethasone for patients with relapsed and&#xD;
      refractory myeloma. In addition, the study will assess whether this combination with&#xD;
      effective for patients with multiple myeloma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 23, 2014</start_date>
  <completion_date type="Actual">March 14, 2018</completion_date>
  <primary_completion_date type="Actual">November 8, 2017</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>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D): Selinexor on Days 1, 8 and 15 when given in combination with Lipodox 20 mg/m^2 and Dexamethasone 40 mg.&#xD;
Dose level 1: 40 mg in combination with Lipodox and Dexamethasone.&#xD;
Dose level 2: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone.&#xD;
Dose level 2m: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone.&#xD;
Dose level 3m: 80 mg (D1,3,8,10) in combination with Lipodox and Dexamethasone.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Response Rate (ORR) - All Participants</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>ORR per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): &gt;/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by &gt;/= 90% or to &lt; 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level &lt;100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and &lt;/= 5% plasma cells in bone marrow. Stable Disease: Not meeting criteria for CR, VGPR, PR, or progressive disease. Minimal response: Less than 50% decrease in M protein. Not evaluable: Cannot be measured because enough information has not been collected.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Response Rate (ORR) -All Participants Treated at Recommended Phase 2 Dose</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Determine the overall response rate per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): &gt;/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by &gt;/= 90% or to &lt; 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level &lt;100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and &lt;/= 5% plasma cells in bone marrow.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Selinexor, Liposomal Doxorubicin and Dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D).&#xD;
After the initial screening visit and registration in the study, participants will receive Selinexor orally at a dose of 80 mg along with dexamethasone for 1 day. One week later, patients will receive weekly selinexor at a starting dose from 60 mg once a week to 80 mg twice a week in combination with pegylated liposomal doxorubicin at a starting dose of 20 mg/m², and dexamethasone 40 mg orally weekly.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Selinexor</intervention_name>
    <description>Selinexor orally as outlined in the study treatment arm.</description>
    <arm_group_label>Selinexor, Liposomal Doxorubicin and Dexamethasone</arm_group_label>
    <other_name>KPT-330</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liposomal doxorubicin</intervention_name>
    <description>Pegylated liposomal doxorubicin at a starting dose of 20 mb/m² as outlined in the treatment arm.</description>
    <arm_group_label>Selinexor, Liposomal Doxorubicin and Dexamethasone</arm_group_label>
    <other_name>Lipodox</other_name>
    <other_name>LD</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Participants will be instructed to take Dexamethasone 40 mg (10 tablets) orally once weekly with meals (ideally with breakfast to minimize insomnia). Participants older than 75 years and patients previously intolerant to 40 mg dosage will be allowed to receive 20 mg (5 tablets) once a week.</description>
    <arm_group_label>Selinexor, Liposomal Doxorubicin and Dexamethasone</arm_group_label>
    <other_name>Decadron</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with relapsed and refractory multiple myeloma who have received at least 2&#xD;
             prior therapies which must include lenalidomide and a proteasome inhibitor. Patients&#xD;
             must have disease refractory to the most recent therapy. Refractory myeloma is defined&#xD;
             as progressive disease during or within 60 days of last therapy. Patients must have&#xD;
             previously received or be ineligible for (or refused) autologous stem cell transplant.&#xD;
&#xD;
          -  Must have measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL) or urine (≥ 0.2&#xD;
             g excreted in a 24-hour urine collection sample) or by free light chain (involved free&#xD;
             light chain greater than 100 mg/L).&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. ECOG 2 allowed if&#xD;
             due to bone disease&#xD;
&#xD;
          -  Must have an echocardiogram or multigated acquisition (MUGA) scan indicating left&#xD;
             ventricular ejection fraction (LVEF) ≥ 50% within 42 days prior to first dose of study&#xD;
             drug&#xD;
&#xD;
          -  Adequate hematological function&#xD;
&#xD;
          -  Adequate hepatic function within 14 days prior to loading phase (day -14)&#xD;
&#xD;
          -  Adequate renal function within 14 days prior to loading: estimated creatinine&#xD;
             clearance of ≥ 30 mL/min, (Cockcroft and Gault)&#xD;
&#xD;
          -  Female patients of child-bearing potential must agree to use dual methods of&#xD;
             contraception and have a negative serum pregnancy test at screening. Male patients&#xD;
             must use an effective barrier method of contraception if sexually active with a female&#xD;
             of child-bearing potential. For both male and female patients, effective methods of&#xD;
             contraception must be used throughout the study and for three months following the&#xD;
             last dose.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant or lactating&#xD;
&#xD;
          -  Radiation, chemotherapy, or immunotherapy or any other approved anticancer therapy ≤2&#xD;
             weeks prior to day -7 (beginning of loading phase)&#xD;
&#xD;
          -  Major surgery within four weeks before Day -7&#xD;
&#xD;
          -  Myocardial infarct within 6 months before enrollment, New York Heart Association&#xD;
             (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled&#xD;
             ventricular arrhythmias, clinically significant pericardial disease, or&#xD;
             electrocardiographic evidence of acute ischemic or active conduction system&#xD;
             abnormalities&#xD;
&#xD;
          -  Prior cumulative exposure to doxorubicin (including liposomal preparation) &gt; 350mg/m^2&#xD;
&#xD;
          -  Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals&#xD;
             within one week prior to first dose; patients with controlled infection or on&#xD;
             prophylactic antibiotics are permitted in the study&#xD;
&#xD;
          -  Known to be HIV seropositive&#xD;
&#xD;
          -  Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C&#xD;
             virus (HCV) RNA or HBsAg (HBV surface antigen)&#xD;
&#xD;
          -  Any underlying condition that would significantly interfere with the absorption of an&#xD;
             oral medication&#xD;
&#xD;
          -  Grade &gt;2 peripheral neuropathy at baseline (within 14 days prior to loading phase (day&#xD;
             -7))&#xD;
&#xD;
          -  Serious psychiatric or medical conditions that could interfere with treatment&#xD;
&#xD;
          -  Participation in an investigational anti-cancer study within 3 weeks prior to day&#xD;
             -7(beginning of loading phase)&#xD;
&#xD;
          -  Concurrent therapy with approved or investigational anticancer therapeutic&#xD;
&#xD;
          -  Coagulation problems and active bleeding in the last month&#xD;
&#xD;
          -  Previous allogeneic transplant within 6 months and have evidence of clinically&#xD;
             significant graft versus host disease&#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>Rachid Baz, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>H. Lee Moffitt Cancer Center and Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center and Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barbara Ann Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <results_first_submitted>August 30, 2018</results_first_submitted>
  <results_first_submitted_qc>January 28, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">February 19, 2019</results_first_posted>
  <last_update_submitted>December 29, 2022</last_update_submitted>
  <last_update_submitted_qc>December 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Relapsed</keyword>
  <keyword>Refractory</keyword>
  <keyword>Myeloma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 31, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT02186834/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited at Moffitt Cancer Center and Karmanos Cancer Center September 2014 through May 2017.</recruitment_details>
      <pre_assignment_details>6 of the 14 participants treated at RP2D moved on from Dose 2m arm in the dose escalation portion of study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1</title>
          <description>Dose 1: Participants were administered Lipodox 20 mg/m^2 via IV on Day 1 of cycle. Selinexor at 40 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
        <group group_id="P2">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2</title>
          <description>Dose 2: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
        <group group_id="P3">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1m</title>
          <description>Dose 1m: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 60 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
        <group group_id="P4">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2m</title>
          <description>Dose 2m: Participants were administered Lipodox 20mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
        <group group_id="P5">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 3m</title>
          <description>Dose 3m: Participants were administered Lipodox 20mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,3, 8 and 10 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
        <group group_id="P6">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- RP2D</title>
          <description>Phase 2 Dose: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Dose Escalation</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" 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 group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Treatment at RP2D</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="13"/>
              </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 group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Died prior to treatment</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who received treatment</population>
      <group_list>
        <group group_id="B1">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone</title>
          <description>Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D)</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="27"/>
          </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="60" lower_limit="49" upper_limit="76"/>
                  </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="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Tolerated Dose (MTD)</title>
        <description>Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D): Selinexor on Days 1, 8 and 15 when given in combination with Lipodox 20 mg/m^2 and Dexamethasone 40 mg.&#xD;
Dose level 1: 40 mg in combination with Lipodox and Dexamethasone.&#xD;
Dose level 2: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone.&#xD;
Dose level 2m: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone.&#xD;
Dose level 3m: 80 mg (D1,3,8,10) in combination with Lipodox and Dexamethasone.</description>
        <time_frame>Up to 12 months</time_frame>
        <population>All participants treated during dose escalation</population>
        <group_list>
          <group group_id="O1">
            <title>Selinexor, Liposomal Doxorubicin and Dexamethasone</title>
            <description>Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D)</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose (MTD)</title>
          <description>Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D): Selinexor on Days 1, 8 and 15 when given in combination with Lipodox 20 mg/m^2 and Dexamethasone 40 mg.&#xD;
Dose level 1: 40 mg in combination with Lipodox and Dexamethasone.&#xD;
Dose level 2: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone.&#xD;
Dose level 2m: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone.&#xD;
Dose level 3m: 80 mg (D1,3,8,10) in combination with Lipodox and Dexamethasone.</description>
          <population>All participants treated during dose escalation</population>
          <units>mg</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR) - All Participants</title>
        <description>ORR per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): &gt;/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by &gt;/= 90% or to &lt; 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level &lt;100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and &lt;/= 5% plasma cells in bone marrow. Stable Disease: Not meeting criteria for CR, VGPR, PR, or progressive disease. Minimal response: Less than 50% decrease in M protein. Not evaluable: Cannot be measured because enough information has not been collected.</description>
        <time_frame>Up to 24 months</time_frame>
        <population>All participants</population>
        <group_list>
          <group group_id="O1">
            <title>Selinexor, Liposomal Doxorubicin and Dexamethasone</title>
            <description>Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D)</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) - All Participants</title>
          <description>ORR per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): &gt;/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by &gt;/= 90% or to &lt; 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level &lt;100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and &lt;/= 5% plasma cells in bone marrow. Stable Disease: Not meeting criteria for CR, VGPR, PR, or progressive disease. Minimal response: Less than 50% decrease in M protein. Not evaluable: Cannot be measured because enough information has not been collected.</description>
          <population>All participants</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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>&gt;/= Very Good Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;/= Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;/= Minimal Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Evaluable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR) -All Participants Treated at Recommended Phase 2 Dose</title>
        <description>Determine the overall response rate per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): &gt;/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by &gt;/= 90% or to &lt; 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level &lt;100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and &lt;/= 5% plasma cells in bone marrow.</description>
        <time_frame>Up to 24 months</time_frame>
        <population>All participants treated at recommended phase 2 dose, regardless of when they joined the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Selinexor, Liposomal Doxorubicin and Dexamethasone</title>
            <description>Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D)</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) -All Participants Treated at Recommended Phase 2 Dose</title>
          <description>Determine the overall response rate per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): &gt;/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by &gt;/= 90% or to &lt; 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level &lt;100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and &lt;/= 5% plasma cells in bone marrow.</description>
          <population>All participants treated at recommended phase 2 dose, regardless of when they joined the study.</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="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>&gt;/= Very Good Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;/= Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;/= Minimal Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Evaluable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 years, 2 months</time_frame>
      <desc>All Adverse Events (AEs) and Serious Adverse Events (SAEs) at all grade levels, regardless of causality have been reported in this section. One participant died prior to treatment but after consent. Only participants who received treatment were considered at Risk for Serious and Other Adverse Events.</desc>
      <group_list>
        <group group_id="E1">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1</title>
          <description>Dose 1: Participants were administered Lipodox 20 mg/m^2 via IV on Day 1 of cycle. Selinexor at 40 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
        <group group_id="E2">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2</title>
          <description>Dose 2: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle.&#xD;
Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
        <group group_id="E3">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1m</title>
          <description>Dose 1m: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 60 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
        <group group_id="E4">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2m</title>
          <description>Dose 2m: Participants were administered Lipodox 20mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
        <group group_id="E5">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 3m</title>
          <description>Dose 3m: Participants were administered Lipodox 20mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,3, 8 and 10 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
        <group group_id="E6">
          <title>Selinexor, Liposomal Doxorubicin and Dexamethasone- RP2D</title>
          <description>Phase 2 Dose: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fecal incontinence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumocystitis pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Streptococcal pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>RSV pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pleural infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>CPK increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Musculoskeletal deformity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="8" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Thrombotic thrombocytopenia purpura</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear and labyrinth disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Watering eyes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fecal incontinence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>General disorders - Other</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pleural infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Skin Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="12" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="5" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" events="9" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E5" events="3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neurtrophil count decreased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>CPK increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="5" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>General muscle weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorders -Other</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Osteonecrosis of jaw</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Amnesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Psychiatric disorders - Other</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal and urinary disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Renal calculi</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Reproductive system and breast disorders - Other</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Adult respiratory distress syndrom</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders -Other</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythroderma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Palmer-plantar erythrodesthesia syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </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. Rachid Baz</name_or_title>
      <organization>H. Lee Moffitt Cancer Center and Research Institute</organization>
      <phone>813-745-8212</phone>
      <email>rachid.baz@moffitt.org</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/NCT02186834
org study id: MCC-17814
nct id: NCT02186834
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The main purpose of this study is to determine the recommended doses of selinexor in
      combination with liposomal doxorubicin and dexamethasone for patients with relapsed and
      refractory myeloma. In addition, the study will assess whether this combination with
      effective for patients with multiple myeloma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: Up to 12 months
description: Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D): Selinexor on Days 1, 8 and 15 when given in combination with Lipodox 20 mg/m^2 and Dexamethasone 40 mg.
Dose level 1: 40 mg in combination with Lipodox and Dexamethasone.
Dose level 2: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone.
Dose level 2m: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone.
Dose level 3m: 80 mg (D1,3,8,10) in combination with Lipodox and Dexamethasone.
measure: Overall Response Rate (ORR) - All Participants
time frame: Up to 24 months
description: ORR per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): >/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >/= 90% or to < 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow. Stable Disease: Not meeting criteria for CR, VGPR, PR, or progressive disease. Minimal response: Less than 50% decrease in M protein. Not evaluable: Cannot be measured because enough information has not been collected.
measure: Overall Response Rate (ORR) -All Participants Treated at Recommended Phase 2 Dose
time frame: Up to 24 months
description: Determine the overall response rate per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): >/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >/= 90% or to < 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow.
arm group label: Selinexor, Liposomal Doxorubicin and Dexamethasone
arm group type: Experimental
description: Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D).
After the initial screening visit and registration in the study, participants will receive Selinexor orally at a dose of 80 mg along with dexamethasone for 1 day. One week later, patients will receive weekly selinexor at a starting dose from 60 mg once a week to 80 mg twice a week in combination with pegylated liposomal doxorubicin at a starting dose of 20 mg/m², and dexamethasone 40 mg orally weekly.
intervention type: Drug
intervention name: Selinexor
description: Selinexor orally as outlined in the study treatment arm.
arm group label: Selinexor, Liposomal Doxorubicin and Dexamethasone
other name: KPT-330
intervention type: Drug
intervention name: Liposomal doxorubicin
description: Pegylated liposomal doxorubicin at a starting dose of 20 mb/m² as outlined in the treatment arm.
arm group label: Selinexor, Liposomal Doxorubicin and Dexamethasone
other name: Lipodox
other name: LD
intervention type: Drug
intervention name: Dexamethasone
description: Participants will be instructed to take Dexamethasone 40 mg (10 tablets) orally once weekly with meals (ideally with breakfast to minimize insomnia). Participants older than 75 years and patients previously intolerant to 40 mg dosage will be allowed to receive 20 mg (5 tablets) once a week.
arm group label: Selinexor, Liposomal Doxorubicin and Dexamethasone
other name: Decadron
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rachid Baz, M.D.
role: Principal Investigator
affiliation: H. Lee Moffitt Cancer Center and Research Institute
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 