Clinical Trials /

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

NCT04562870

Description:

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.

Related Conditions:
  • Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: XPORT-MF-035
  • SECONDARY ID: 2020-003809-60
  • NCT ID: NCT04562870

Conditions

  • Myelofibrosis

Interventions

DrugSynonymsArms
SelinexorArm S: Selinexor

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm S: SelinexorExperimentalParticipants 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.
  • Selinexor
Arm PC: Physician's Choice TreatmentActive ComparatorParticipants 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.

    Eligibility Criteria

            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.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure: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
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure: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)
    Safety Issue:
    Description:
    Measure:Percentage of Participants with Spleen Volume Reduction of ≥25% (SVR25) Assessed by IRC
    Time Frame:From Baseline up to Week 48
    Safety Issue:
    Description:
    Measure:Overall Survival (OS)
    Time Frame:From Baseline up to 12 months after end of treatment (approximately 60 months)
    Safety Issue:
    Description:
    Measure: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)
    Safety Issue:
    Description:
    Measure: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)
    Safety Issue:
    Description:
    Measure: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)
    Safety Issue:
    Description:
    Measure: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)
    Safety Issue:
    Description:
    Measure:Overall Response Rate (ORR) Assessed by IWG-MRT
    Time Frame:From Baseline up to 28 Days after last dose (approximately 48 months)
    Safety Issue:
    Description:
    Measure: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)
    Safety Issue:
    Description:
    Measure: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)
    Safety Issue:
    Description:
    Measure: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)
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Karyopharm Therapeutics Inc

    Trial Keywords

    • Myelofibrosis
    • Selinexor
    • Total Symptom Score
    • Spleen Volume Reduction
    • Anemia response
    • TSS50
    • SVR35
    • SVR25
    • KPT-330
    • JAK1
    • JAK2
    • XPOVIO
    • SINE
    • XPORT-MF-035
    • Karyopharm

    Last Updated

    June 16, 2021