xml: <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/NCT05980806</url>
    </required_header>
    <id_info>
      <org_study_id>XPORT-MF-044</org_study_id>
      <nct_id>NCT05980806</nct_id>
    </id_info>
    <brief_title>A Study of Selinexor Monotherapy in Subjects With JAK Inhibitor (JAKi)-naïve Myelofibrosis and Moderate Thrombocytopenia</brief_title>
    <official_title>A Phase 2 Study to Evaluate the Efficacy and Safety of Selinexor Monotherapy in Subjects With JAK Inhibitor (JAKi)-naïve Myelofibrosis and Moderate Thrombocytopenia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Karyopharm Therapeutics Inc</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Karyopharm Therapeutics Inc</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The main purpose of this Phase 2 study is to evaluate the efficacy of selinexor in&#xD;
        participants with myelofibrosis (MF) and moderate thrombocytopenia based on spleen volume&#xD;
        reduction (SVR). Additional efficacy parameters and safety will also be assessed during the&#xD;
        study.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">March 2024</start_date>
    <completion_date type="Anticipated">October 2028</completion_date>
    <primary_completion_date type="Anticipated">April 2026</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>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Percentage of Participants with Spleen Volume Reduction of Greater Than or Equal to (&gt;=) 35% (SVR35 Response) as measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan</measure>
      <time_frame>At Week 24</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with Treatment-emergent Adverse Events (TEAEs), Severity of TEAEs, Treatment Related Adverse Events (TRAEs) and Serious Adverse Events (SAEs)</measure>
      <time_frame>From start of drug administration up to 30 days after the last dose of study treatment (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of Participants with Total Symptom Score (TSS) Reduction of &gt;= 50% (TSS50 Response) Measured by the Myelofibrosis Symptom Assessment Form (MFSAF) V4.0</measure>
      <time_frame>At Week 24</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of Participants with Anemia Response , as per the International Working Group Myeloproliferative Neoplasms Research and Treatment and European Leukemia Network (IWG-MRT and ELN) Criteria</measure>
      <time_frame>At Week 24</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>From date of randomization to the date of death due to any cause or EoS (assessed at approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Response Rate (ORR) as per IWG MRT and ELN criteria</measure>
      <time_frame>From Cycle 1 Day 1 (28-day cycle) up to EoS (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of Participants with SVR35 at Any Time Point as Measured by MRI or CT Scan</measure>
      <time_frame>From Baseline to EoS (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of Participants with TSS50 at Any Time as measured by the MFSAF V4.0</measure>
      <time_frame>From Baseline to EoS (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>SVR35 Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)</measure>
      <time_frame>From Baseline up to EoS (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>TSS50 Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)</measure>
      <time_frame>From Baseline up to EoS (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anemia Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)</measure>
      <time_frame>From Baseline up to EoS (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>SVR35 Response in Participants who received ruxolitinib or pacritinib as add-on treatment to selinexor</measure>
      <time_frame>From Baseline up to EoS (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>TSS50 Response in Participants who received ruxolitinib or pacritinib as add-on treatment to selinexor</measure>
      <time_frame>From Baseline up to EoS (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anemia Response in Participants who received ruxolitinib or pacritinib as add-on treatment to selinexor</measure>
      <time_frame>From Baseline up to EoS (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area Under the Concentration-time Curve (AUC) of Selinexor</measure>
      <time_frame>Predose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum Plasma Concentration (Cmax) of Selinexor</measure>
      <time_frame>Predose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time at Which Cmax is Achieved (Tmax) of Selinexor</measure>
      <time_frame>Predose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Receptor Occupancy or Exportin 1 (XPO1) mRNA Induction</measure>
      <time_frame>From Baseline up to EoS (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of Participants with at least Grade 1 Decrease in Bone Marrow Fibrosis</measure>
      <time_frame>From Baseline up to EoS (approximately 48 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with Treatment-emergent Adverse Events (TEAEs), Severity of TEAEs, Treatment Related Adverse Events (TRAEs) and Serious Adverse Events (SAEs) in Participants who received ruxolitinib or pacritinib as add-on treatment to selinexor</measure>
      <time_frame>From start of drug administration up to 30 days after the last dose of study treatment (approximately 48 months)</time_frame>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">118</enrollment>
    <condition>Myelofibrosis</condition>
    <condition>Moderate Thrombocytopenia</condition>
    <arm_group>
      <arm_group_label>Selinexor 60 mg (Arm 1)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Selinexor 40 mg (Arm 2)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive selinexor 40 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Selinexor 60 mg (Optional Extension Arm)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first. This arm may be initiated following a review of efficacy and safety data from the selinexor 60 mg treatment arm (Arm 1).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Selinexor 40 mg (Optional Extension Arm)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive selinexor 40 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first. This arm may be initiated following a review of efficacy and safety data from the selinexor 40 mg treatment arm (Arm 2).</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Selinexor</intervention_name>
      <description>Participants will receive selinexor 60 mg oral tablets QW.</description>
      <arm_group_label>Selinexor 60 mg (Arm 1)</arm_group_label>
      <arm_group_label>Selinexor 60 mg (Optional Extension Arm)</arm_group_label>
      <other_name>KPT-330</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Selinexor</intervention_name>
      <description>Participants will receive selinexor 40 mg oral tablets QW.</description>
      <arm_group_label>Selinexor 40 mg (Arm 2)</arm_group_label>
      <arm_group_label>Selinexor 40 mg (Optional Extension Arm)</arm_group_label>
      <other_name>KPT-330</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria:&#xD;
  &#xD;
            -  A diagnosis of MF or post-ET or post-PV MF according to the 2016 World Health&#xD;
               Organization (WHO) classification of MPN, confirmed by the most recent local pathology&#xD;
               report.&#xD;
  &#xD;
            -  Measurable splenomegaly during the screening period as demonstrated by spleen volume&#xD;
               of greater than equal to (&gt;=) 450 cubic square centimeter (cm^3) by MRI or CT scan&#xD;
               (results from MRI or CT imaging performed within 28 days prior to screening are&#xD;
               acceptable).&#xD;
  &#xD;
            -  Participants with DIPSS risk category of intermediate-1 with symptoms, or&#xD;
               intermediate-2, or high-risk.&#xD;
  &#xD;
            -  ECOG Performance Status less than or equal to (&lt;=) 2.&#xD;
  &#xD;
            -  Platelet count of 50 x 10^9/L to 100 x 10^9/L without platelet transfusion within 7&#xD;
               days prior to the first dose of the study drug.&#xD;
  &#xD;
            -  Absolute neutrophil count (ANC) &gt;=1.0 × 10^9/L without need for growth factors within&#xD;
               7 days prior to the first dose of the study drug.&#xD;
  &#xD;
            -  Adequate liver function as defined by the following: aspartate transaminase (AST) and&#xD;
               alanine aminotransferase (ALT) &lt;= 2.5 × upper limit normal (ULN) and serum total&#xD;
               bilirubin &lt;= 3× ULN.&#xD;
  &#xD;
            -  Calculated creatinine clearance (CrCl) greater than (&gt;) 15 milliliter per minute&#xD;
               (mL/min) based on the Cockcroft and Gault formula.&#xD;
  &#xD;
            -  Active symptoms of MF as determined by presence of at least 2 symptoms with a score &gt;=&#xD;
               3 or total score of &gt;= 10 at screening using the MFSAF V4.0.&#xD;
  &#xD;
            -  Participants must provide bone marrow biopsy samples (samples obtained up to 3 months&#xD;
               prior to C1D1 are permitted) at screening and during the study.&#xD;
  &#xD;
            -  Participants currently not eligible for stem cell transplantation.&#xD;
  &#xD;
            -  Participants must be willing to complete the MFSAF V4.0 daily during the study for&#xD;
               evaluating the symptom response (i.e., TSS50).&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
            -  More than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase).&#xD;
  &#xD;
            -  Previous treatment with JAK inhibitors for MF.&#xD;
  &#xD;
            -  Previous treatment with selinexor or other XPO1 inhibitors.&#xD;
  &#xD;
            -  Female participants who are pregnant or lactating.&#xD;
  &#xD;
            -  Prior splenectomy, or splenic radiation within 6 months prior to C1D1.&#xD;
  &#xD;
            -  History of pulmonary hypertension.&#xD;
  &#xD;
            -  History of myocardial infarction, unstable angina, percutaneous transluminal coronary&#xD;
               angioplasty (PTCA) or coronary artery bypass graft (CABG), cerebrovascular accident&#xD;
               (stroke or transient ischemic attack [TIA]), ventricular arrhythmias, congestive heart&#xD;
               failure New York Heart Association (NYHA) class &gt; 2 within 6 months of C1D1.&#xD;
  &#xD;
            -  Participants unable to tolerate two forms of antiemetics prior to each dose for the&#xD;
               first two cycles, and the option to continue thereafter.&#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_contact>
      <last_name>Karyopharm Medical Information</last_name>
      <phone>(888) 209-9326</phone>
      <email>clinicaltrials@karyopharm.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Myelofibrosis</keyword>
    <keyword>Selinexor</keyword>
    <keyword>Total Symptom Score</keyword>
    <keyword>Myelofibrosis Symptom Assessment Form</keyword>
    <keyword>Spleen Volume Reduction</keyword>
    <keyword>TSS50</keyword>
    <keyword>SVR35</keyword>
    <keyword>JAK2</keyword>
    <keyword>KPT-330</keyword>
    <keyword>Pacritinib</keyword>
    <keyword>Ruxolitinib</keyword>
    <keyword>Thrombocytopenia</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Thrombocytopenia</mesh_term>
      <mesh_term>Primary Myelofibrosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05980806
  org study id: XPORT-MF-044
  nct id: NCT05980806
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  The main purpose of this Phase 2 study is to evaluate the efficacy of selinexor in
        participants with myelofibrosis (MF) and moderate thrombocytopenia based on spleen volume
        reduction (SVR). Additional efficacy parameters and safety will also be assessed during the
        study.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Percentage of Participants with Spleen Volume Reduction of Greater Than or Equal to (>=) 35% (SVR35 Response) as measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan
  time frame: At Week 24
  measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs), Severity of TEAEs, Treatment Related Adverse Events (TRAEs) and Serious Adverse Events (SAEs)
  time frame: From start of drug administration up to 30 days after the last dose of study treatment (approximately 48 months)
  measure: Proportion of Participants with Total Symptom Score (TSS) Reduction of >= 50% (TSS50 Response) Measured by the Myelofibrosis Symptom Assessment Form (MFSAF) V4.0
  time frame: At Week 24
  measure: Proportion of Participants with Anemia Response , as per the International Working Group Myeloproliferative Neoplasms Research and Treatment and European Leukemia Network (IWG-MRT and ELN) Criteria
  time frame: At Week 24
  measure: Overall Survival (OS)
  time frame: From date of randomization to the date of death due to any cause or EoS (assessed at approximately 48 months)
  measure: Overall Response Rate (ORR) as per IWG MRT and ELN criteria
  time frame: From Cycle 1 Day 1 (28-day cycle) up to EoS (approximately 48 months)
  measure: Proportion of Participants with SVR35 at Any Time Point as Measured by MRI or CT Scan
  time frame: From Baseline to EoS (approximately 48 months)
  measure: Proportion of Participants with TSS50 at Any Time as measured by the MFSAF V4.0
  time frame: From Baseline to EoS (approximately 48 months)
  measure: SVR35 Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)
  time frame: From Baseline up to EoS (approximately 48 months)
  measure: TSS50 Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)
  time frame: From Baseline up to EoS (approximately 48 months)
  measure: Anemia Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)
  time frame: From Baseline up to EoS (approximately 48 months)
  measure: SVR35 Response in Participants who received ruxolitinib or pacritinib as add-on treatment to selinexor
  time frame: From Baseline up to EoS (approximately 48 months)
  measure: TSS50 Response in Participants who received ruxolitinib or pacritinib as add-on treatment to selinexor
  time frame: From Baseline up to EoS (approximately 48 months)
  measure: Anemia Response in Participants who received ruxolitinib or pacritinib as add-on treatment to selinexor
  time frame: From Baseline up to EoS (approximately 48 months)
  measure: Area Under the Concentration-time Curve (AUC) of Selinexor
  time frame: Predose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
  measure: Maximum Plasma Concentration (Cmax) of Selinexor
  time frame: Predose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
  measure: Time at Which Cmax is Achieved (Tmax) of Selinexor
  time frame: Predose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
  measure: Duration of Receptor Occupancy or Exportin 1 (XPO1) mRNA Induction
  time frame: From Baseline up to EoS (approximately 48 months)
  measure: Proportion of Participants with at least Grade 1 Decrease in Bone Marrow Fibrosis
  time frame: From Baseline up to EoS (approximately 48 months)
  measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs), Severity of TEAEs, Treatment Related Adverse Events (TRAEs) and Serious Adverse Events (SAEs) in Participants who received ruxolitinib or pacritinib as add-on treatment to selinexor
  time frame: From start of drug administration up to 30 days after the last dose of study treatment (approximately 48 months)
  arm group label: Selinexor 60 mg (Arm 1)
  arm group type: Experimental
  description: Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first.
  arm group label: Selinexor 40 mg (Arm 2)
  arm group type: Experimental
  description: Participants will receive selinexor 40 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first.
  arm group label: Selinexor 60 mg (Optional Extension Arm)
  arm group type: Experimental
  description: Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first. This arm may be initiated following a review of efficacy and safety data from the selinexor 60 mg treatment arm (Arm 1).
  arm group label: Selinexor 40 mg (Optional Extension Arm)
  arm group type: Experimental
  description: Participants will receive selinexor 40 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first. This arm may be initiated following a review of efficacy and safety data from the selinexor 40 mg treatment arm (Arm 2).
  intervention type: Drug
  intervention name: Selinexor
  description: Participants will receive selinexor 60 mg oral tablets QW.
  arm group label: Selinexor 60 mg (Arm 1)
  arm group label: Selinexor 60 mg (Optional Extension Arm)
  other name: KPT-330
  intervention type: Drug
  intervention name: Selinexor
  description: Participants will receive selinexor 40 mg oral tablets QW.
  arm group label: Selinexor 40 mg (Arm 2)
  arm group label: Selinexor 40 mg (Optional Extension Arm)
  other name: KPT-330
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Karyopharm Medical Information
  phone: (888) 209-9326
  email: clinicaltrials@karyopharm.com
  responsible party type: Sponsor
  mesh term: Thrombocytopenia
  mesh term: Primary Myelofibrosis
  sharing ipd: Undecided