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A Study of Selinexor Monotherapy in Subjects With JAK Inhibitor (JAKi)-naïve Myelofibrosis and Moderate Thrombocytopenia

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ClinicalTrials.gov Identifier: NCT05980806
Recruitment Status : Not yet recruiting
First Posted : August 8, 2023
Last Update Posted : August 23, 2023
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Myelofibrosis Moderate Thrombocytopenia Drug: Selinexor Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : March 2024
Estimated Primary Completion Date : April 2026
Estimated Study Completion Date : October 2028

Resource links provided by the National Library of Medicine

Drug Information available for: Selinexor

Arms and Interventions
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Arm Intervention/treatment
Experimental: Selinexor 60 mg (Arm 1)
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.
 Drug: Selinexor
Participants will receive selinexor 60 mg oral tablets QW.
Other Name: KPT-330
Experimental: Selinexor 40 mg (Arm 2)
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.
 Drug: Selinexor
Participants will receive selinexor 40 mg oral tablets QW.
Other Name: KPT-330
Experimental: Selinexor 60 mg (Optional Extension Arm)
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).
 Drug: Selinexor
Participants will receive selinexor 60 mg oral tablets QW.
Other Name: KPT-330
Experimental: Selinexor 40 mg (Optional Extension Arm)
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).
 Drug: Selinexor
Participants will receive selinexor 40 mg oral tablets QW.
Other Name: KPT-330


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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 ]
  3. 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 ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. Proportion of Participants with TSS50 at Any Time as measured by the MFSAF V4.0 [ Time Frame: From Baseline to EoS (approximately 48 months) ]
  8. SVR35 Response in Participant Subgroups (Including by Gender, Age, and Geographic Region) [ Time Frame: From Baseline up to EoS (approximately 48 months) ]
  9. TSS50 Response in Participant Subgroups (Including by Gender, Age, and Geographic Region) [ Time Frame: From Baseline up to EoS (approximately 48 months) ]
  10. Anemia Response in Participant Subgroups (Including by Gender, Age, and Geographic Region) [ Time Frame: From Baseline up to EoS (approximately 48 months) ]
  11. 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) ]
  12. 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) ]
  13. 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) ]
  14. 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) ]
  15. 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) ]
  16. 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) ]
  17. Duration of Receptor Occupancy or Exportin 1 (XPO1) mRNA Induction [ Time Frame: From Baseline up to EoS (approximately 48 months) ]
  18. Proportion of Participants with at least Grade 1 Decrease in Bone Marrow Fibrosis [ Time Frame: From Baseline up to EoS (approximately 48 months) ]
  19. 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) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • A diagnosis of MF or post-ET or post-PV MF according to the 2016 World Health Organization (WHO) classification of MPN, confirmed by the most recent local pathology report.
  • Measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than equal to (>=) 450 cubic square centimeter (cm^3) by MRI or CT scan (results from MRI or CT imaging performed within 28 days prior to screening are acceptable).
  • Participants with DIPSS risk category of intermediate-1 with symptoms, or intermediate-2, or high-risk.
  • ECOG Performance Status less than or equal to (<=) 2.
  • Platelet count of 50 x 10^9/L to 100 x 10^9/L without platelet transfusion within 7 days prior to the first dose of the study drug.
  • Absolute neutrophil count (ANC) >=1.0 × 10^9/L without need for growth factors within 7 days prior to the first dose of the study drug.
  • Adequate liver function as defined by the following: aspartate transaminase (AST) and alanine aminotransferase (ALT) <= 2.5 × upper limit normal (ULN) and serum total bilirubin <= 3× ULN.
  • Calculated creatinine clearance (CrCl) greater than (>) 15 milliliter per minute (mL/min) based on the Cockcroft and Gault formula.
  • Active symptoms of MF as determined by presence of at least 2 symptoms with a score >= 3 or total score of >= 10 at screening using the MFSAF V4.0.
  • Participants must provide bone marrow biopsy samples (samples obtained up to 3 months prior to C1D1 are permitted) at screening and during the study.
  • Participants currently not eligible for stem cell transplantation.
  • Participants must be willing to complete the MFSAF V4.0 daily during the study for evaluating the symptom response (i.e., TSS50).

Key Exclusion Criteria:

  • More than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase).
  • Previous treatment with JAK inhibitors for MF.
  • Previous treatment with selinexor or other XPO1 inhibitors.
  • Female participants who are pregnant or lactating.
  • Prior splenectomy, or splenic radiation within 6 months prior to C1D1.
  • History of pulmonary hypertension.
  • History of myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG), cerebrovascular accident (stroke or transient ischemic attack [TIA]), ventricular arrhythmias, congestive heart failure New York Heart Association (NYHA) class > 2 within 6 months of C1D1.
  • Participants unable to tolerate two forms of antiemetics prior to each dose for the first two cycles, and the option to continue thereafter.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05980806


Contacts
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Contact: Karyopharm Medical Information (888) 209-9326 clinicaltrials@karyopharm.com

Sponsors and Collaborators
Karyopharm Therapeutics Inc
More Information
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Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT05980806    
Other Study ID Numbers: XPORT-MF-044
First Posted: August 8, 2023    Key Record Dates
Last Update Posted: August 23, 2023
Last Verified: August 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Karyopharm Therapeutics Inc:
Myelofibrosis
Selinexor
Total Symptom Score
Myelofibrosis Symptom Assessment Form
Spleen Volume Reduction
TSS50
 SVR35
JAK2
KPT-330
Pacritinib
Ruxolitinib
Thrombocytopenia
Additional relevant MeSH terms:
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Thrombocytopenia
Primary Myelofibrosis
Blood Platelet Disorders
 Hematologic Diseases
Myeloproliferative Disorders
Bone Marrow Diseases