<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/NCT02228525</url>
  </required_header>
  <id_info>
    <org_study_id>14-005</org_study_id>
    <nct_id>NCT02228525</nct_id>
  </id_info>
  <brief_title>Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes</brief_title>
  <official_title>A Phase II Study of the Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Karyopharm Therapeutics Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to see if selinexor will improve the blood counts and bone&#xD;
      marrow function in people with your type of MDS.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 27, 2014</start_date>
  <completion_date type="Actual">April 6, 2021</completion_date>
  <primary_completion_date type="Actual">April 6, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Best Overall Response Rate</measure>
    <time_frame>2 years</time_frame>
    <description>Using a Simon's two-stage minimax design, this trial will accrue a maximum of 20 patients. Early termination may occur if no responses are observed in the first 13 patients. If at least one response is observed, the trial will continue to the maximum sample size. At the end of the trial, the treatment strategy will be considered promising in this patient population if at least 3 patients achieve a response. The type I and type II errors are set at 0.10.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response Duration</measure>
    <time_frame>2 years</time_frame>
    <description>Response duration will be calculated among patients who achieve a response of HI, mCR, PR or CR using Kaplan-Meier methodology. Median duration of response and the corresponding 95% confidence interval will be estimated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>2 years</time_frame>
    <description>Overall survival from the time of study enrollment will be calculated using Kaplan-Meier methodology. Overall survival curves will be displayed for the study population along with selected quantiles and corresponding 95% confidence intervals of survival.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants Evaluated for Adverse Events</measure>
    <time_frame>2 years</time_frame>
    <description>The safety and tolerability of Selinexor and ST will be evaluated by means of drug related AE reports, physical examinations, and laboratory safety evaluations. Common Terminology Criteria for Adverse Events (CTCAE) V4.03 will be used for grading of AEs.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Myelodysplastic Syndromes</condition>
  <arm_group>
    <arm_group_label>selinexor (KPT-330)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>selinexor (KPT-330)</intervention_name>
    <arm_group_label>selinexor (KPT-330)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent in accordance with federal, local, and institutional&#xD;
             guidelines&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Patients with Myelodysplastic Syndromes refractory (primary or acquired resistance) to&#xD;
             hypomethylating agents(decitabine or 5-azacytidine). At least 4 1- month cycles of&#xD;
             prior decitabine or SGI-110 OR 6 1-month cycles of 5-azacytidine (IV, subcutaneous, or&#xD;
             oral is required unless the patient has progressive disease prior to completing the&#xD;
             required number of cycles.&#xD;
&#xD;
          -  Histologically confirmed diagnosis of a Myelodysplastic Syndrome, meeting criteria for&#xD;
             any subtype in the FAB or WHO classification systems with any IPSS score.&#xD;
&#xD;
          -  Patients with MDS who relapse after allogeneic stem cell transplant are eligible if&#xD;
             they received standard dose decitabine or 5-azacytidine prior to or after stem cell&#xD;
             transplant as defined in inclusion criteria 3.&#xD;
&#xD;
          -  If patient has undergone prior allogeneic stem cell transplant, they must be greater&#xD;
             than 100 days post transplant and have ≤ grade 2 graft-versus-host disease&#xD;
&#xD;
          -  There is no upper limit on the number of prior treatments provided all&#xD;
             inclusion/exclusion criteria are met.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2&#xD;
&#xD;
          -  Patients receiving erythropoietin (darbepoetin, epoetin alfa) must be on a stable dose&#xD;
             and with stable transfusion requirement or hemoglobin level during the 8 weeks prior&#xD;
             to study entry.&#xD;
&#xD;
          -  Adequate hepatic function within 21 days prior to C1D1: total bilirubin &lt;2 times the&#xD;
             upper limit of normal (ULN), asparate aminotransferase (AST) &lt;2.5 times ULN and&#xD;
             alanine aminotransferase (ALT) &lt;2.5 times ULN.&#xD;
&#xD;
          -  Adequate renal function within 21 days prior to C1D1: estimated creatinine clearance&#xD;
             of ≥ 30 mL/min, calculated using the formula of Cockcroft and Gault.&#xD;
&#xD;
          -  Female patients of child-bearing potential must agree to use dual methods of&#xD;
             contraception and have a negative serum pregnancy test at screening, and male patients&#xD;
             must use an effective barrier method of contraception if sexually active with a female&#xD;
             of child-bearing potential. Acceptable methods of contraception are condoms with&#xD;
             contraceptive foam, oral, implantable or injectable contraceptives, contraceptive&#xD;
             patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is&#xD;
             surgically sterilized or post-menopausal. For both male and female patients, effective&#xD;
             methods of contraception must be used throughout the study and for three months&#xD;
             following the last dose.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are pregnant or lactating;&#xD;
&#xD;
          -  Chemotherapy or immunotherapy or any other anticancer therapy ≤3 weeks prior to cycle&#xD;
             1 day 1. Hydroxyurea may be continued until 72 hours prior to first dose and at least&#xD;
             24 hours before the baseline bone marrow aspiration is performed;&#xD;
&#xD;
          -  Major surgery within four weeks before Day 1;&#xD;
&#xD;
          -  Unstable cardiovascular function defined as symptomatic ischemia, uncontrolled&#xD;
             clinically significant conduction abnormalities (ie: ventricular tachycardia on&#xD;
             antiarrhythmics are excluded and 1st degree AV block or asymptomatic LAFB/RBBB will&#xD;
             not be excluded), congestive heart failure (CHF) of NYHA Class ≥3, or myocardial&#xD;
             infarction (MI) within 3 months;&#xD;
&#xD;
          -  Uncontrolled active infection requiring systemic antibiotics, antivirals, or&#xD;
             antifungals within one week prior to first dose; Prophylactic antimicrobials are&#xD;
             permitted.&#xD;
&#xD;
          -  Known to be HIV seropositive;&#xD;
&#xD;
          -  Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or&#xD;
             HBsAg (HBV surface antigen);&#xD;
&#xD;
          -  Patients with another active malignancy. Asymptomatic sites of disease are not&#xD;
             considered active. Treated or untreated sites of disease may be considered inactive if&#xD;
             they are stable for at least 2 months and are not expected to require therapy for 4&#xD;
             months.&#xD;
&#xD;
          -  Patients with significantly diseased or obstructed gastrointestinal tract or&#xD;
             uncontrolled vomiting or diarrhea.&#xD;
&#xD;
          -  Grade ≥2 peripheral neuropathy at baseline (within 21 days prior to cycle 1 day 1).&#xD;
&#xD;
          -  History of seizures, movement disorders or cerebrovascular accident within the past 1&#xD;
             years prior to cycle 1 day 1.&#xD;
&#xD;
          -  Patients with macular degeneration with markedly decreased visual acuity, patients&#xD;
             with markedly decreased visual acuity (no specific etiology) or uncontrolled glaucoma.&#xD;
&#xD;
          -  Patients who are significantly below their ideal body weight (BMI &lt; 17)..&#xD;
&#xD;
          -  Serious psychiatric or medical conditions that could interfere with treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Virginia Klimek, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>August 27, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2014</study_first_posted>
  <results_first_submitted>February 11, 2022</results_first_submitted>
  <results_first_submitted_qc>February 11, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">March 9, 2022</results_first_posted>
  <last_update_submitted>February 11, 2022</last_update_submitted>
  <last_update_submitted_qc>February 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Selinexor (KPT-330)</keyword>
  <keyword>Selective Inhibitor of Nuclear Export (SINE)</keyword>
  <keyword>14-005</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 25, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/25/NCT02228525/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Selinexor (KPT-330)</title>
          <description>Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months.&#xD;
selinexor (KPT-330)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Selinexor (KPT-330)</title>
          <description>Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months.&#xD;
selinexor (KPT-330)</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="77" lower_limit="70" upper_limit="81"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Best Overall Response Rate</title>
        <description>Using a Simon's two-stage minimax design, this trial will accrue a maximum of 20 patients. Early termination may occur if no responses are observed in the first 13 patients. If at least one response is observed, the trial will continue to the maximum sample size. At the end of the trial, the treatment strategy will be considered promising in this patient population if at least 3 patients achieve a response. The type I and type II errors are set at 0.10.</description>
        <time_frame>2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Selinexor (KPT-330)</title>
            <description>Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months.&#xD;
selinexor (KPT-330)</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Response Rate</title>
          <description>Using a Simon's two-stage minimax design, this trial will accrue a maximum of 20 patients. Early termination may occur if no responses are observed in the first 13 patients. If at least one response is observed, the trial will continue to the maximum sample size. At the end of the trial, the treatment strategy will be considered promising in this patient population if at least 3 patients achieve a response. The type I and type II errors are set at 0.10.</description>
          <units>Percentage of participants with response</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26" lower_limit="10" upper_limit="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Response Duration</title>
        <description>Response duration will be calculated among patients who achieve a response of HI, mCR, PR or CR using Kaplan-Meier methodology. Median duration of response and the corresponding 95% confidence interval will be estimated.</description>
        <time_frame>2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Selinexor (KPT-330)</title>
            <description>Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months.&#xD;
selinexor (KPT-330)</description>
          </group>
        </group_list>
        <measure>
          <title>Response Duration</title>
          <description>Response duration will be calculated among patients who achieve a response of HI, mCR, PR or CR using Kaplan-Meier methodology. Median duration of response and the corresponding 95% confidence interval will be estimated.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.3" lower_limit="2.1" upper_limit="7.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Overall survival from the time of study enrollment will be calculated using Kaplan-Meier methodology. Overall survival curves will be displayed for the study population along with selected quantiles and corresponding 95% confidence intervals of survival.</description>
        <time_frame>2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Selinexor (KPT-330)</title>
            <description>Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months.&#xD;
selinexor (KPT-330)</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Overall survival from the time of study enrollment will be calculated using Kaplan-Meier methodology. Overall survival curves will be displayed for the study population along with selected quantiles and corresponding 95% confidence intervals of survival.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.5" lower_limit="6.7" upper_limit="12.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants Evaluated for Adverse Events</title>
        <description>The safety and tolerability of Selinexor and ST will be evaluated by means of drug related AE reports, physical examinations, and laboratory safety evaluations. Common Terminology Criteria for Adverse Events (CTCAE) V4.03 will be used for grading of AEs.</description>
        <time_frame>2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Selinexor (KPT-330)</title>
            <description>Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months.&#xD;
selinexor (KPT-330)</description>
          </group>
        </group_list>
        <measure>
          <title>Participants Evaluated for Adverse Events</title>
          <description>The safety and tolerability of Selinexor and ST will be evaluated by means of drug related AE reports, physical examinations, and laboratory safety evaluations. Common Terminology Criteria for Adverse Events (CTCAE) V4.03 will be used for grading of AEs.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Selinexor (KPT-330)</title>
          <description>Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months.&#xD;
selinexor (KPT-330)</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="25" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Nausea or vomiting</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Increased alanine aminotransferase</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Decreased white blood cell count</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Decreased neutrophil count</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Decreased platelet count</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia or weight loss</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Eytan Stein, MD</name_or_title>
      <organization>Memorial Sloan Kettering Cancer Center</organization>
      <phone>646-608-3749</phone>
      <email>steine@mskcc.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02228525
org study id: 14-005
nct id: NCT02228525
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
The purpose of this study is to see if selinexor will improve the blood counts and bone
      marrow function in people with your type of MDS.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Best Overall Response Rate
time frame: 2 years
description: Using a Simon's two-stage minimax design, this trial will accrue a maximum of 20 patients. Early termination may occur if no responses are observed in the first 13 patients. If at least one response is observed, the trial will continue to the maximum sample size. At the end of the trial, the treatment strategy will be considered promising in this patient population if at least 3 patients achieve a response. The type I and type II errors are set at 0.10.
measure: Response Duration
time frame: 2 years
description: Response duration will be calculated among patients who achieve a response of HI, mCR, PR or CR using Kaplan-Meier methodology. Median duration of response and the corresponding 95% confidence interval will be estimated.
measure: Overall Survival
time frame: 2 years
description: Overall survival from the time of study enrollment will be calculated using Kaplan-Meier methodology. Overall survival curves will be displayed for the study population along with selected quantiles and corresponding 95% confidence intervals of survival.
measure: Participants Evaluated for Adverse Events
time frame: 2 years
description: The safety and tolerability of Selinexor and ST will be evaluated by means of drug related AE reports, physical examinations, and laboratory safety evaluations. Common Terminology Criteria for Adverse Events (CTCAE) V4.03 will be used for grading of AEs.
arm group label: selinexor (KPT-330)
arm group type: Experimental
description: Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months.
intervention type: Drug
intervention name: selinexor (KPT-330)
arm group label: selinexor (KPT-330)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Virginia Klimek, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
country: United States
url: http://www.mskcc.org/
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 