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A Study to Evaluate Safety and Efficacy of Selinexor Versus Treatment of Physician's Choice in Participants With Previously Treated Myelofibrosis

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ClinicalTrials.gov Identifier: NCT04562870
Recruitment Status : Recruiting
First Posted : September 24, 2020
Last Update Posted : December 23, 2021
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Tracking Information
First Submitted Date  ICMJE September 9, 2020
First Posted Date  ICMJE September 24, 2020
Last Update Posted Date December 23, 2021
Actual Study Start Date  ICMJE March 17, 2021
Estimated Primary Completion Date May 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 6, 2021)
Percentage of Participants with Spleen Volume Reduction of Greater Than or Equal to (≥) 35 Percent (%) (SVR35) Assessed by Independent Review Committee (IRC) [ Time Frame: From Baseline up to Week 48 ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 23, 2020)
Percentage of Participants with Spleen Volume Reduction of Greater Than or Equal to (≥) 35 Percent (%) (SVR35): Assessed by Independent Review Committee (IRC) [ Time Frame: From Baseline up to Week 48 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2021)
  • Percentage of Participants with Total Symptom Score Reduction of ≥50% (TSS50) Measured by Myelofibrosis Symptom Assessment Form (MFSAF) V4.0, Based on Local Assessment [ Time Frame: From Baseline up to end of last cycle (approximately 48 months) ]
  • Percentage of Participants with Spleen Volume Reduction of ≥25% (SVR25) Assessed by IRC [ Time Frame: From Baseline up to Week 48 ]
  • Overall Survival (OS) [ Time Frame: From Baseline up to 12 months after end of treatment (approximately 60 months) ]
  • Percentage of Participants with Anemia Response Assessed by International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT ) [ Time Frame: From Baseline up to 28 Days after last dose (approximately 48 months) ]
  • Duration of Spleen Volume Reduction of ≥35% (SVR35) Assessed by IRC [ Time Frame: From Baseline up to 28 Days after last dose (approximately 48 months) ]
  • Duration of Spleen Volume Reduction of ≥25% (SVR25) Assessed by IRC [ Time Frame: From Baseline up to 28 Days after last dose (approximately 48 months) ]
  • Duration of Total Symptom Score is ≥50% (TSS50) Based on Local Assessment [ Time Frame: From Baseline up to 28 Days after last dose (approximately 48 months) ]
  • Overall Response Rate (ORR) Assessed by IWG-MRT [ Time Frame: From Baseline up to 28 Days after last dose (approximately 48 months) ]
  • Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity Grade ≥3, Serious Adverse event (SAEs), and AEs Leading to Treatment Discontinuation [ Time Frame: From first dose of study treatment up to 30 days after end of treatment (approximately 48 months) ]
  • Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-time Curve (AUC) of Selinexor [ Time Frame: Cycle 2 Day 1: 1, 2, 4, 6, and 24 hours post dose (each cycle is 28 days) ]
  • PK Parameter: Maximum Plasma Concentration (Cmax) of Selinexor [ Time Frame: Cycle 2 Day 1: 1, 2, 4, 6, and 24 hours post dose (each cycle is 28 days) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2020)
  • Total Symptom Score Reduction of ≥50% (TSS50) Measured by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) [ Time Frame: From Baseline up to end of last cycle (approximately 48 months) ]
  • Percentage of Participants with Spleen Volume Reduction of ≥25% (SVR25): Assessed by IRC [ Time Frame: From Baseline up to Week 48 ]
  • Overall Survival (OS) [ Time Frame: From Baseline up to 12 months after end of treatment (approximately 60 months) ]
  • Percentage of Participants with Anemia Response: Assessed by IRC [ Time Frame: From Baseline up to 28 Days after last dose (approximately 48 months) ]
  • Number of Participants With Any Treatment-emergent Adverse Events (AEs) (TEAEs) by Severity Grade ≥3, Serious Adverse event (SAEs), and AEs Leading to Treatment Discontinuation [ Time Frame: From first dose of study treatment up to 30 days after end of treatment (approximately 48 months) ]
  • Duration of Spleen Volume Reduction of ≥35% [ Time Frame: From Baseline up to 28 Days after last dose (approximately 48 months) ]
  • Duration of Spleen Volume Reduction of ≥25% [ Time Frame: From Baseline up to 28 Days after last dose (approximately 48 months) ]
  • Duration of Total Symptom Score is ≥50% [ Time Frame: From Baseline up to 28 Days after last dose (approximately 48 months) ]
  • Overall Response Rate (ORR) [ Time Frame: From Baseline up to 28 Days after last dose (approximately 48 months) ]
  • Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Selinexor [ Time Frame: Cycle 2 Day 1: 1, 2, 4, 6, and 24 hours post dose (each cycle is 28 days) ]
  • PK Parameter: Area Under the Plasma Concentration-time Curve (AUC) of Selinexor [ Time Frame: Cycle 2 Day 1: 1, 2, 4, 6, and 24 hours post dose (each cycle is 28 days) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Safety and Efficacy of Selinexor Versus Treatment of Physician's Choice in Participants With Previously Treated Myelofibrosis
Official Title  ICMJE A Phase 2, Randomized, Open-Label, Multicenter Study to Evaluate Safety and Efficacy of Single Agent Selinexor Versus Treatment of Physician's Choice in Patients With Previously Treated Myelofibrosis
Brief Summary This is a Phase 2, multicenter, two-arm, open-label study to evaluate the safety and efficacy of selinexor versus treatment per physician's choice (PC) in participants with myelofibrosis (MF) who had at least 6 months of treatment with a Janus kinase (JAK)1/2 inhibitor. Study participants will be randomized in a 1:1 ratio to either receive selinexor or physicians' choice of treatment.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myelofibrosis
Intervention  ICMJE
  • Drug: Selinexor
    Unit Dose Strength: 20 mg; Dose Formulation: Tablet; Dosage Level: 60 mg, QW; Route of Administration: Oral
  • Other: Physician's Choice Treatment
    Physician's choice treatment may include ruxolitinib retreatment, fedratinib, chemotherapy (e.g., hydroxyurea), anagrelide, corticosteroid, hematopoietic growth factor, immunomodulatory agent, androgen, interferon (all as per clinical practice) and may include supportive care only with no MF treatment; no investigational therapies are allowed.
Study Arms  ICMJE
  • Experimental: Arm S: Selinexor
    Participants with MF who had previously received at least 6 months of treatment with JAK 1/2 inhibitor will receive Selinexor 60 mg oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle.
    Intervention: Drug: Selinexor
  • Active Comparator: Arm PC: Physician's Choice Treatment
    Participants with MF who had previously received at least 6 months of treatment with JAK 1/2 inhibitor will receive Physician's choice treatment which will be administered as per clinical practice.
    Intervention: Other: Physician's Choice Treatment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 6, 2021)
112
Original Estimated Enrollment  ICMJE
 (submitted: September 23, 2020)
138
Estimated Study Completion Date  ICMJE May 31, 2023
Estimated Primary Completion Date May 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • A diagnosis of primary MF or post-essential thrombocythemia (ET) or post-polycythemia (PV) MF according to the 2016 World Health Organization (WHO) classification of myeloproliferative neoplasms (MPN), confirmed by the most recent local pathology report.
  • Previous treatment with JAK inhibitors for at least 6 months.
  • Measurable splenomegaly during the screening period as demonstrated by spleen volume of ≥450 centimeter cube (cm^3) by magnetic resonance imaging (MRI) or computerized tomography (CT) scan.
  • Relapsed, Refractory or Intolerant to JAK inhibitors as defined as meeting one of the criteria below:

    • less than (<) 35% spleen volume reduction by MRI or CT-scan (from baseline) or
    • <50% decrease in spleen size by palpation (from baseline) or an increase of at least 3 cm with the spleen at least 5 cm below the left costal margin or
    • Spleen volume increase greater than (>) 25% from nadir or a return to within 10% of baseline after any initial response or
    • Treatment with JAK inhibitor was complicated by development of red blood cells (RBC) transfusion requirement (2 units per month for 2 month); or grade 3 thrombocytopenia, anemia, hematoma/hemorrhage; or grade 2 non-hematologic toxicity while on JAK inhibitors
  • Participants ≥18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) less than or equal to (≤) 2.
  • Platelet count ≥100*10^9 per liter (/L).
  • Absolute neutrophil count (ANC) ≥1.5*10^9/L.
  • Serum direct bilirubin ≤1.5*upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5*ULN.
  • Calculated creatinine clearance (CrCl) >15 milliliter (mL)/minute (min) based on the Cockcroft and Gault formula.
  • Participants with active hepatitis B virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 International Units (IU)/mL.
  • Participants with untreated hepatitis C virus (HCV) are eligible if there is a documentation of negative viral load per institutional standard.
  • Participants with history of human immunodeficiency virus (HIV) are eligible if they have cluster of differentiation 4 (CD4)+ T-cell counts ≥350 cells/microliter (mcL), negative viral load per institutional standard, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.
  • Female participants of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective methods of contraception throughout the study and for one month following the last dose of study treatment. Childbearing potential excludes: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy.
  • Male participants who are sexually active must use highly effective methods of contraception throughout the study and for one month following the last dose of study treatment. Male Participants must agree not to donate sperm during the study treatment period.
  • Participants must sign written informed consent in accordance with federal, local and institutional guidelines.

Exclusion Criteria:

  • >5% blasts in peripheral blood or >10% blasts in bone marrow (i.e., accelerated phase).
  • Previous treatment with selinexor or other exportin 1 (XPO1) inhibitors.
  • Use of any standard or experimental anti-MF therapy <21 days prior to Cycle 1 Day 1 (hydroxyurea is allowed).
  • Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of selinexor (Example: vomiting, or diarrhea that is Common Terminology Criteria for Adverse Events (CTCAE) grade >1).
  • Received strong cytochrome P450 3A (CYP3A) inhibitors ≤7 days prior to selinexor dosing or strong CYP3A inducers ≤14 days prior to selinexor dosing.
  • Major surgery <28 days prior to cycle 1 day 1 (C1D1).
  • Uncontrolled (ie, clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral).
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participants safety, prevent the participant from giving informed consent, or being compliant with the study procedures.
  • Female participants who are pregnant or lactating.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jatin Shah Chief Medical Officer, MD (617) 658-0600 jshah@karyopharm.com
Contact: Sharon Shacham Chief Scientific Officer, PhD (617) 658-0600 sshacham@karyopharm.com
Listed Location Countries  ICMJE Greece,   Hungary,   Italy,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04562870
Other Study ID Numbers  ICMJE XPORT-MF-035
2020-003809-60 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Karyopharm Therapeutics Inc
Study Sponsor  ICMJE Karyopharm Therapeutics Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Karyopharm Therapeutics Inc
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP