<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/NCT02249091</url>
  </required_header>
  <id_info>
    <org_study_id>SAIL</org_study_id>
    <secondary_id>2014-000526-37</secondary_id>
    <nct_id>NCT02249091</nct_id>
  </id_info>
  <brief_title>A Phase II Study of Selinexor Plus Cytarabine and Idarubicin in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)</brief_title>
  <official_title>An Investigator-Initiated Study To Evaluate Ara-C and Idarubicin in Combination With the Selective Inhibitor Of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Relapsed Or Refractory AML</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GSO Global Clinical Research BV</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Karyopharm Therapeutics Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>GSO Global Clinical Research BV</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute Myeloid Leukemia (AML) is currently treated with chemotherapy by combining several&#xD;
      drugs with different ways of inhibiting the cell growth. In this trial, standard&#xD;
      chemotherapeutics that have proven their effectiveness for years, Ara-C and Idarubicin, will&#xD;
      be combined with a new drug called Selinexor.&#xD;
&#xD;
      Selinexor inhibits the growth of cancer cells by keeping certain proteins in the nucleus&#xD;
      which control the cell growth.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">July 31, 2018</completion_date>
  <primary_completion_date type="Actual">July 31, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>In the initial protocol, 25 patients are included in the clinical trial on the schedule described as cohort 1. After an amendment 15 further patients are included on the schedule described as cohort 2.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With CR/CRi = Overall Reponse Rate</measure>
    <time_frame>1-2 induction cycles (4 - 8 weeks)</time_frame>
    <description>Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of complete response (CR) or morphologic complete response with incomplete blood count recovery (CRi), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:&#xD;
CR: Absolute Neutrophil count (ANC) &gt;1.0x10^9/L, Platelet count &gt;100x10^9/L, Bone marrow blasts &lt;5%, no Auer rods, no evidence of extramedullary disease.&#xD;
CRi: Same as CR, but ANC may be &lt;1.0x10^9/L and/or Platelet count &lt;100x10^9/L.&#xD;
Patients with morphologic leukemia free-state (MLFS) were included in the group of responders. MLFS: Bone marrow blasts &lt;5%, no Auer rods, no evidence of extramedullary disease.&#xD;
The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Partial Remission (PR) = Rate of PR</measure>
    <time_frame>1-2 induction cycles (4 - 8 weeks)</time_frame>
    <description>Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of partial remission(PR) as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:&#xD;
PR: Absolute Neutrophil count (ANC) &gt;1.0x10^9/L, Platelet count &gt;100x10^9/L, at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt;5% with persistent Auer rods.&#xD;
The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)</measure>
    <time_frame>1-2 induction cycles (4 - 8 weeks)</time_frame>
    <description>Percentage of patients being transplanted after induction therapy (stem cell transplantation)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early Death Rate</measure>
    <time_frame>1 induction cycle (4 weeks)</time_frame>
    <description>Early death was defined as death before the end of the first induction cycle.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Time from registration to event, max 2 years</time_frame>
    <description>Overall survival (OS) was calculated from the date of informed consent to the date of death. Patients still alive at the end of follow-up were censored at the last date of follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse-Free Survival</measure>
    <time_frame>Time from registration to event, max 2 years</time_frame>
    <description>Relapse-free survival (RFS) was calculated from the date of CR/CRi until death or relapse, whichever occurred first. Patients were censored on the date of the last follow-up if they were alive without relapse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-Free Survival</measure>
    <time_frame>Time from registration to event, max 2 years</time_frame>
    <description>Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival</measure>
    <time_frame>Time from registration to event, max 2 years</time_frame>
    <description>Progression-free survival (PFS) was calculated from the time of informed consent to the date of recurrence or death, whichever occurred first. Patients were censored at the date of the last follow-up visit if they were alive without relapse.&#xD;
Disease progression was defined as presence of &gt;50% increase in bone marrow blasts to a level of at least 50% and/or a doubling of the percentage of peripheral blood blasts to a level of at least 50%.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Acute Myeloid Leukemia (Relapsed/Refractory)</condition>
  <arm_group>
    <arm_group_label>Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All enrolled patients are treated with cytarabine at a dose of 100 mg/m² continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m^2 iv (day 1,3,5) every 4 weeks and selinexor for up to 2 induction cycles. If a second cycle is applied idarubicin is only given on day 1 and 3.&#xD;
Selinexor is administered at a dose of 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per induction cycle).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All enrolled patients are treated with cytarabine at a dose of 100 mg/m^2 continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m^2 iv (day 1,3,5) every 4 weeks and selinexor for up to 2 induction cycles. If a second cycle is applied idarubicin is only given on day 1 and 3.&#xD;
Selinexor is administered at a flat dose of 60 mg twice weekly orally in weeks 1-3 of a 4-week cycle starting on day 2 (total of 6 doses per induction cycle).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Selinexor</intervention_name>
    <description>Patients receive Selinexor as specified in arm/group description (8 doses of 40 mg/m^2 or 6 doses of 60 mg per induction cycle).</description>
    <arm_group_label>Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin</arm_group_label>
    <arm_group_label>Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin</arm_group_label>
    <other_name>KPT-330</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Idarubicin</intervention_name>
    <description>Infusion, iv, 10 mg/m^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2</description>
    <arm_group_label>Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin</arm_group_label>
    <arm_group_label>Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <description>Continuous infusion day 1 to 7, 100 mg/m^2, iv,</description>
    <arm_group_label>Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin</arm_group_label>
    <arm_group_label>Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin</arm_group_label>
    <other_name>Ara-C</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Cytological or histological diagnosis of AML with the exception of promyelocytic&#xD;
             leukemia (AML M3)&#xD;
&#xD;
          2. Patients must have relapsed/refractory disease (relapse after stem cell&#xD;
             transplantation is permitted) as defined as:&#xD;
&#xD;
               1. patients with &lt;PR after first cycle of induction chemotherapy, or&#xD;
&#xD;
               2. patients with &lt;CR(i) after second cycle of induction chemotherapy, or&#xD;
&#xD;
               3. patients who relapse after conventional chemotherapy or&#xD;
&#xD;
               4. patients who have undergone a single stem cell transplantation and who have&#xD;
                  relapse of their AML.&#xD;
&#xD;
          3. Men and women aged ≥18 years and eligible for standard dose of chemotherapy (7+3);&#xD;
&#xD;
          4. A period of at least 3 weeks needs to have elapsed since last treatment (with the&#xD;
             exception of hydroxyurea) before participating in this study. Hydroxyurea induction&#xD;
             therapy to reduce peripheral blast counts is permitted prior to initiation of&#xD;
             treatment on protocol. Treatment may begin in &lt;3 weeks from last treatment if deemed&#xD;
             in the best interest of the patient after discussion with the PI of the study;&#xD;
&#xD;
          5. ECOG performance status ≤ 2&#xD;
&#xD;
          6. Serum biochemical values with the following limits unless considered due to leukemia:&#xD;
             creatinine ≤2 mg/dl; total bilirubin ≤2x ULN, unless increase is due to hemolysis or&#xD;
             congenital disorder; transaminases (SGPT or SGOT) ≤2.5x ULN.&#xD;
&#xD;
          7. Ability to swallow and retain oral medication;&#xD;
&#xD;
          8. Ability to understand and provide signed informed consent;&#xD;
&#xD;
          9. Cardiac ejection fraction must be &gt;/=50% (by echocardiography).&#xD;
&#xD;
         10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory&#xD;
             tests, and other study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Treatment with any investigational agent within four weeks.&#xD;
&#xD;
          2. Cumulative anthracycline dose (daunorubicin or equivalent) &gt;360 mg/m^2&#xD;
&#xD;
          3. HIV infection&#xD;
&#xD;
          4. Presence of any medical or psychiatric condition which may limit full compliance with&#xD;
             the study, including but not limited to:&#xD;
&#xD;
          5. Presence of CNS leukemia&#xD;
&#xD;
          6. Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from&#xD;
             surgery.&#xD;
&#xD;
          7. For patients after SCT as part of prior treatment:&#xD;
&#xD;
               1. Necessity of immunosuppressive drugs&#xD;
&#xD;
               2. GvHD &gt; grade 1&#xD;
&#xD;
          8. Any of the following within the 12 months prior to study drug administration:&#xD;
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass&#xD;
             graft, symptomatic congestive heart failure, cerebrovascular accident or transient&#xD;
             ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic&#xD;
             event.&#xD;
&#xD;
          9. Ongoing cardiac dysrhythmias of NCI CTCAE &gt;/= Grade 2.&#xD;
&#xD;
         10. Other severe acute or chronic medical or psychiatric condition, or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or study&#xD;
             drug administration, or may interfere with the interpretation of study results, and in&#xD;
             the judgment of the investigator would make the patient inappropriate for entry into&#xD;
             this study.&#xD;
&#xD;
         11. Clinically significant bleeding within 1 month&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Universitätsklinikum Frankfurt</name>
      <address>
        <city>Frankfurt am Main</city>
        <state>Hessen</state>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <state>Niedersachsen</state>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Hamburg-Eppendorf</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <results_first_submitted>April 27, 2021</results_first_submitted>
  <results_first_submitted_qc>August 1, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 25, 2021</results_first_posted>
  <last_update_submitted>August 1, 2021</last_update_submitted>
  <last_update_submitted_qc>August 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytarabine</mesh_term>
    <mesh_term>Idarubicin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 13, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT02249091/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 25, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT02249091/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>43 patients were registered in the clinical trial at 3 sites. One patient was a screening failure. Of the remaining 42 patients, the first 27 patients were treated in cohort 1 (Selinexor dosed by Body Surface Area [BSA] 40 mg/m^2 per dose) and the other 15 patients were treated in cohort 2 (flat dose of Selinexor of 60 mg per dose).</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin</title>
          <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin</title>
          <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1.&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Stable disease with following SCT</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ongoing bone marrow aplasia, periph. pancytopenia</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>CR with subsequent donor lymphocyte infusion</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Refractory AML</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin</title>
          <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin</title>
          <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1.&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="27"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="42"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.0" spread="15.18"/>
                    <measurement group_id="B2" value="58.5" spread="13.55"/>
                    <measurement group_id="B3" value="55.6" spread="14.62"/>
                  </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="11"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Leukemia diagnosis</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>De Novo Acute Myeloid Leukemia (AML)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Therapy-induced AML</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Secondary AML</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior stem cell transplantation (SCT)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With CR/CRi = Overall Reponse Rate</title>
        <description>Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of complete response (CR) or morphologic complete response with incomplete blood count recovery (CRi), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:&#xD;
CR: Absolute Neutrophil count (ANC) &gt;1.0x10^9/L, Platelet count &gt;100x10^9/L, Bone marrow blasts &lt;5%, no Auer rods, no evidence of extramedullary disease.&#xD;
CRi: Same as CR, but ANC may be &lt;1.0x10^9/L and/or Platelet count &lt;100x10^9/L.&#xD;
Patients with morphologic leukemia free-state (MLFS) were included in the group of responders. MLFS: Bone marrow blasts &lt;5%, no Auer rods, no evidence of extramedullary disease.&#xD;
The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).</description>
        <time_frame>1-2 induction cycles (4 - 8 weeks)</time_frame>
        <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1.&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With CR/CRi = Overall Reponse Rate</title>
          <description>Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of complete response (CR) or morphologic complete response with incomplete blood count recovery (CRi), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:&#xD;
CR: Absolute Neutrophil count (ANC) &gt;1.0x10^9/L, Platelet count &gt;100x10^9/L, Bone marrow blasts &lt;5%, no Auer rods, no evidence of extramedullary disease.&#xD;
CRi: Same as CR, but ANC may be &lt;1.0x10^9/L and/or Platelet count &lt;100x10^9/L.&#xD;
Patients with morphologic leukemia free-state (MLFS) were included in the group of responders. MLFS: Bone marrow blasts &lt;5%, no Auer rods, no evidence of extramedullary disease.&#xD;
The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).</description>
          <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</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 group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Partial Remission (PR) = Rate of PR</title>
        <description>Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of partial remission(PR) as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:&#xD;
PR: Absolute Neutrophil count (ANC) &gt;1.0x10^9/L, Platelet count &gt;100x10^9/L, at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt;5% with persistent Auer rods.&#xD;
The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).</description>
        <time_frame>1-2 induction cycles (4 - 8 weeks)</time_frame>
        <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1.&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Partial Remission (PR) = Rate of PR</title>
          <description>Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of partial remission(PR) as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:&#xD;
PR: Absolute Neutrophil count (ANC) &gt;1.0x10^9/L, Platelet count &gt;100x10^9/L, at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts &lt;5% with persistent Auer rods.&#xD;
The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).</description>
          <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</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 group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)</title>
        <description>Percentage of patients being transplanted after induction therapy (stem cell transplantation)</description>
        <time_frame>1-2 induction cycles (4 - 8 weeks)</time_frame>
        <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1.&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)</title>
          <description>Percentage of patients being transplanted after induction therapy (stem cell transplantation)</description>
          <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</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 group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Early Death Rate</title>
        <description>Early death was defined as death before the end of the first induction cycle.</description>
        <time_frame>1 induction cycle (4 weeks)</time_frame>
        <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1.&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Early Death Rate</title>
          <description>Early death was defined as death before the end of the first induction cycle.</description>
          <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</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 group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Overall survival (OS) was calculated from the date of informed consent to the date of death. Patients still alive at the end of follow-up were censored at the last date of follow-up.</description>
        <time_frame>Time from registration to event, max 2 years</time_frame>
        <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1.&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Overall survival (OS) was calculated from the date of informed consent to the date of death. Patients still alive at the end of follow-up were censored at the last date of follow-up.</description>
          <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.6" lower_limit="4.2" upper_limit="NA">Not available due to low number of events</measurement>
                    <measurement group_id="O2" value="8.0" lower_limit="0.89" upper_limit="NA">Not available due to low number of events</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relapse-Free Survival</title>
        <description>Relapse-free survival (RFS) was calculated from the date of CR/CRi until death or relapse, whichever occurred first. Patients were censored on the date of the last follow-up if they were alive without relapse.</description>
        <time_frame>Time from registration to event, max 2 years</time_frame>
        <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1.&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Relapse-Free Survival</title>
          <description>Relapse-free survival (RFS) was calculated from the date of CR/CRi until death or relapse, whichever occurred first. Patients were censored on the date of the last follow-up if they were alive without relapse.</description>
          <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.9" lower_limit="2.8" upper_limit="NA">Not available due to low number of events</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="4.1" upper_limit="NA">Not available due to low number of events</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Event-Free Survival</title>
        <description>Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi.</description>
        <time_frame>Time from registration to event, max 2 years</time_frame>
        <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1.&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Event-Free Survival</title>
          <description>Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi.</description>
          <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" lower_limit="2.9" upper_limit="12.6"/>
                    <measurement group_id="O2" value="4.3" lower_limit="0.9" upper_limit="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-Free Survival</title>
        <description>Progression-free survival (PFS) was calculated from the time of informed consent to the date of recurrence or death, whichever occurred first. Patients were censored at the date of the last follow-up visit if they were alive without relapse.&#xD;
Disease progression was defined as presence of &gt;50% increase in bone marrow blasts to a level of at least 50% and/or a doubling of the percentage of peripheral blood blasts to a level of at least 50%.</description>
        <time_frame>Time from registration to event, max 2 years</time_frame>
        <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin</title>
            <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1.&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-Free Survival</title>
          <description>Progression-free survival (PFS) was calculated from the time of informed consent to the date of recurrence or death, whichever occurred first. Patients were censored at the date of the last follow-up visit if they were alive without relapse.&#xD;
Disease progression was defined as presence of &gt;50% increase in bone marrow blasts to a level of at least 50% and/or a doubling of the percentage of peripheral blood blasts to a level of at least 50%.</description>
          <population>All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.3" lower_limit="2.3" upper_limit="26.3"/>
                    <measurement group_id="O2" value="4.3" lower_limit="0.9" upper_limit="12.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months.</time_frame>
      <desc>All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin</title>
          <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin</title>
          <description>Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows:&#xD;
Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle).&#xD;
Idarubcin: i.v. infusion, 10 mg/m^2, on days 1,3,5 in cycle 1.&#xD;
Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m^2&#xD;
Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>NCI-CTCAE v4.03</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Bone marrow hypocellular</sub_title>
                <description>Bone marrow aplasia</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Asystole</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>General weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>SIRS</sub_title>
                <description>Systemic inflammatory response syndrome</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>GvHD</sub_title>
                <description>Graft-versus-host-disease</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hemophagocytosis syndrome</sub_title>
                <description>Lymphohistiocytic syndrome, assessed as related to selinexor; cause of patient's death according to autopsy report: hemophagocytosis syndrome with acute cardiac decompensation</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <description>Neutropenia</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Stroke</sub_title>
                <description>Reported as Multiple Brain Infarctions</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Subarachnoidal hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>NCI-CTCAE v4.03</default_vocab>
        <default_assessment>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="27" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="30" subjects_affected="23" subjects_at_risk="27"/>
                <counts group_id="E2" events="27" subjects_affected="5" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="33" subjects_affected="20" subjects_at_risk="27"/>
                <counts group_id="E2" events="27" subjects_affected="5" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Left ventricular systolic dysfunction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="49" subjects_affected="23" subjects_at_risk="27"/>
                <counts group_id="E2" events="19" subjects_affected="13" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="99" subjects_affected="24" subjects_at_risk="27"/>
                <counts group_id="E2" events="32" subjects_affected="11" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="46" subjects_affected="22" subjects_at_risk="27"/>
                <counts group_id="E2" events="13" subjects_affected="9" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="19" subjects_affected="12" subjects_at_risk="27"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="27"/>
                <counts group_id="E2" events="10" subjects_affected="7" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Oral hemorrhage</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="23" subjects_affected="18" subjects_at_risk="27"/>
                <counts group_id="E2" events="15" subjects_affected="9" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="12" subjects_affected="10" subjects_at_risk="27"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="27"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="9" subjects_affected="5" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="13" subjects_affected="8" subjects_at_risk="27"/>
                <counts group_id="E2" events="7" subjects_affected="4" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="27"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Catheter related infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </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="6" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="21" subjects_affected="17" subjects_at_risk="27"/>
                <counts group_id="E2" events="23" subjects_affected="9" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="33" subjects_affected="19" subjects_at_risk="27"/>
                <counts group_id="E2" events="23" subjects_affected="7" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="14" subjects_affected="12" subjects_at_risk="27"/>
                <counts group_id="E2" events="15" subjects_affected="6" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="40" subjects_affected="22" subjects_at_risk="27"/>
                <counts group_id="E2" events="10" subjects_affected="8" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="27" subjects_affected="17" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </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="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="12" subjects_affected="9" subjects_at_risk="27"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="10" subjects_affected="5" subjects_at_risk="27"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="27"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="13" subjects_affected="10" subjects_at_risk="27"/>
                <counts group_id="E2" events="13" subjects_affected="8" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="16" subjects_affected="12" subjects_at_risk="27"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="27"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Anne L. Kranich</name_or_title>
      <organization>GSO mbH</organization>
      <phone>+494044195460</phone>
      <email>kranich@gsoglobal.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02249091
org study id: SAIL
secondary id: 2014-000526-37
nct id: NCT02249091
lead sponsor: 
collaborator: 
has dmc: No
Acute Myeloid Leukemia (AML) is currently treated with chemotherapy by combining several
      drugs with different ways of inhibiting the cell growth. In this trial, standard
      chemotherapeutics that have proven their effectiveness for years, Ara-C and Idarubicin, will
      be combined with a new drug called Selinexor.

      Selinexor inhibits the growth of cancer cells by keeping certain proteins in the nucleus
      which control the cell growth.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: In the initial protocol, 25 patients are included in the clinical trial on the schedule described as cohort 1. After an amendment 15 further patients are included on the schedule described as cohort 2.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With CR/CRi = Overall Reponse Rate
time frame: 1-2 induction cycles (4 - 8 weeks)
description: Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of complete response (CR) or morphologic complete response with incomplete blood count recovery (CRi), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:
CR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease.
CRi: Same as CR, but ANC may be <1.0x10^9/L and/or Platelet count <100x10^9/L.
Patients with morphologic leukemia free-state (MLFS) were included in the group of responders. MLFS: Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease.
The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).
measure: Number of Participants With Partial Remission (PR) = Rate of PR
time frame: 1-2 induction cycles (4 - 8 weeks)
description: Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of partial remission(PR) as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:
PR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts <5% with persistent Auer rods.
The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).
measure: Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)
time frame: 1-2 induction cycles (4 - 8 weeks)
description: Percentage of patients being transplanted after induction therapy (stem cell transplantation)
measure: Early Death Rate
time frame: 1 induction cycle (4 weeks)
description: Early death was defined as death before the end of the first induction cycle.
measure: Overall Survival
time frame: Time from registration to event, max 2 years
description: Overall survival (OS) was calculated from the date of informed consent to the date of death. Patients still alive at the end of follow-up were censored at the last date of follow-up.
measure: Relapse-Free Survival
time frame: Time from registration to event, max 2 years
description: Relapse-free survival (RFS) was calculated from the date of CR/CRi until death or relapse, whichever occurred first. Patients were censored on the date of the last follow-up if they were alive without relapse.
measure: Event-Free Survival
time frame: Time from registration to event, max 2 years
description: Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi.
measure: Progression-Free Survival
time frame: Time from registration to event, max 2 years
description: Progression-free survival (PFS) was calculated from the time of informed consent to the date of recurrence or death, whichever occurred first. Patients were censored at the date of the last follow-up visit if they were alive without relapse.
Disease progression was defined as presence of >50% increase in bone marrow blasts to a level of at least 50% and/or a doubling of the percentage of peripheral blood blasts to a level of at least 50%.
arm group label: Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin
arm group type: Experimental
description: All enrolled patients are treated with cytarabine at a dose of 100 mg/m² continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m^2 iv (day 1,3,5) every 4 weeks and selinexor for up to 2 induction cycles. If a second cycle is applied idarubicin is only given on day 1 and 3.
Selinexor is administered at a dose of 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per induction cycle).
arm group label: Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin
arm group type: Experimental
description: All enrolled patients are treated with cytarabine at a dose of 100 mg/m^2 continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m^2 iv (day 1,3,5) every 4 weeks and selinexor for up to 2 induction cycles. If a second cycle is applied idarubicin is only given on day 1 and 3.
Selinexor is administered at a flat dose of 60 mg twice weekly orally in weeks 1-3 of a 4-week cycle starting on day 2 (total of 6 doses per induction cycle).
intervention type: Drug
intervention name: Selinexor
description: Patients receive Selinexor as specified in arm/group description (8 doses of 40 mg/m^2 or 6 doses of 60 mg per induction cycle).
arm group label: Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin
arm group label: Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin
other name: KPT-330
intervention type: Drug
intervention name: Idarubicin
description: Infusion, iv, 10 mg/m^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2
arm group label: Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin
arm group label: Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin
intervention type: Drug
intervention name: Cytarabine
description: Continuous infusion day 1 to 7, 100 mg/m^2, iv,
arm group label: Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin
arm group label: Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin
other name: Ara-C
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Cytarabine
mesh term: Idarubicin
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 