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

Primary Purpose

Myelofibrosis, Moderate Thrombocytopenia

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Selinexor
Selinexor
Sponsored by
Karyopharm Therapeutics Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelofibrosis focused on measuring Myelofibrosis, Selinexor, Total Symptom Score, Myelofibrosis Symptom Assessment Form, Spleen Volume Reduction, TSS50, SVR35, JAK2, KPT-330, Pacritinib, Ruxolitinib, Thrombocytopenia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Selinexor 60 mg (Arm 1)

    Selinexor 40 mg (Arm 2)

    Selinexor 60 mg (Optional Extension Arm)

    Selinexor 40 mg (Optional Extension Arm)

    Arm 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.

    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.

    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).

    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).

    Outcomes

    Primary Outcome Measures

    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

    Secondary Outcome Measures

    Number of Participants with Treatment-emergent Adverse Events (TEAEs), Severity of TEAEs, Treatment Related Adverse Events (TRAEs) and Serious Adverse Events (SAEs)
    Proportion of Participants with Total Symptom Score (TSS) Reduction of >= 50% (TSS50 Response) Measured by the Myelofibrosis Symptom Assessment Form (MFSAF) V4.0
    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
    Overall Survival (OS)
    Overall Response Rate (ORR) as per IWG MRT and ELN criteria
    Proportion of Participants with SVR35 at Any Time Point as Measured by MRI or CT Scan
    Proportion of Participants with TSS50 at Any Time as measured by the MFSAF V4.0
    SVR35 Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)
    TSS50 Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)
    Anemia Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)
    SVR35 Response in Participants who received ruxolitinib or pacritinib as add-on treatment to selinexor
    TSS50 Response in Participants who received ruxolitinib or pacritinib as add-on treatment to selinexor
    Anemia Response in Participants who received ruxolitinib or pacritinib as add-on treatment to selinexor
    Area Under the Concentration-time Curve (AUC) of Selinexor
    Maximum Plasma Concentration (Cmax) of Selinexor
    Time at Which Cmax is Achieved (Tmax) of Selinexor
    Duration of Receptor Occupancy or Exportin 1 (XPO1) mRNA Induction
    Proportion of Participants with at least Grade 1 Decrease in Bone Marrow Fibrosis
    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

    Full Information

    First Posted
    July 24, 2023
    Last Updated
    August 21, 2023
    Sponsor
    Karyopharm Therapeutics Inc
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05980806
    Brief Title
    A Study of Selinexor Monotherapy in Subjects With JAK Inhibitor (JAKi)-naïve Myelofibrosis and Moderate Thrombocytopenia
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 2024 (Anticipated)
    Primary Completion Date
    April 2026 (Anticipated)
    Study Completion Date
    October 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Karyopharm Therapeutics Inc

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Myelofibrosis, Moderate Thrombocytopenia
    Keywords
    Myelofibrosis, Selinexor, Total Symptom Score, Myelofibrosis Symptom Assessment Form, Spleen Volume Reduction, TSS50, SVR35, JAK2, KPT-330, Pacritinib, Ruxolitinib, Thrombocytopenia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    118 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Selinexor 60 mg (Arm 1)
    Arm Type
    Experimental
    Arm 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 Title
    Selinexor 40 mg (Arm 2)
    Arm Type
    Experimental
    Arm 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 Title
    Selinexor 60 mg (Optional Extension Arm)
    Arm Type
    Experimental
    Arm 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 Title
    Selinexor 40 mg (Optional Extension Arm)
    Arm Type
    Experimental
    Arm 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(s)
    Selinexor
    Other Intervention Name(s)
    KPT-330
    Intervention Description
    Participants will receive selinexor 60 mg oral tablets QW.
    Intervention Type
    Drug
    Intervention Name(s)
    Selinexor
    Other Intervention Name(s)
    KPT-330
    Intervention Description
    Participants will receive selinexor 40 mg oral tablets QW.
    Primary Outcome Measure Information:
    Title
    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 Measure Information:
    Title
    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)
    Title
    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
    Title
    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
    Title
    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)
    Title
    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)
    Title
    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)
    Title
    Proportion of Participants with TSS50 at Any Time as measured by the MFSAF V4.0
    Time Frame
    From Baseline to EoS (approximately 48 months)
    Title
    SVR35 Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)
    Time Frame
    From Baseline up to EoS (approximately 48 months)
    Title
    TSS50 Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)
    Time Frame
    From Baseline up to EoS (approximately 48 months)
    Title
    Anemia Response in Participant Subgroups (Including by Gender, Age, and Geographic Region)
    Time Frame
    From Baseline up to EoS (approximately 48 months)
    Title
    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)
    Title
    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)
    Title
    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)
    Title
    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)
    Title
    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)
    Title
    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)
    Title
    Duration of Receptor Occupancy or Exportin 1 (XPO1) mRNA Induction
    Time Frame
    From Baseline up to EoS (approximately 48 months)
    Title
    Proportion of Participants with at least Grade 1 Decrease in Bone Marrow Fibrosis
    Time Frame
    From Baseline up to EoS (approximately 48 months)
    Title
    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)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Karyopharm Medical Information
    Phone
    (888) 209-9326
    Email
    clinicaltrials@karyopharm.com

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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

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