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

Sponsor
Karyopharm Therapeutics Inc (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04562870
Collaborator
(none)
112
27
2
26.4
4.1
0.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
112 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 17, 2021
Anticipated Primary Completion Date :
May 31, 2023
Anticipated Study Completion Date :
May 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm S: Selinexor

Participants with MF who had previously received at least 6 months of treatment with JAK 1/2 inhibitor will receive a dose of selinexor 80 mg in first 2 cycles followed by selinexor 60 mg in subsequent cycles orally on Days 1, 8, 15, and 22 of each 28-day cycle to participants on Arm S.

Drug: Selinexor
Unit Dose Strength: 20 mg; Dose Formulation: Tablet; Dosage Level: 60 or 80 mg, QW; Route of Administration: Oral

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.

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.

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants with Spleen Volume Reduction of Greater Than or Equal to (≥) 35 Percent (%) (SVR35) Assessed by Independent Review Committee (IRC) [From Baseline up to Week 48]

Secondary Outcome Measures

  1. Percentage of Participants with Total Symptom Score Reduction of ≥50% (TSS50) Measured by Myelofibrosis Symptom Assessment Form (MFSAF) V4.0, Based on Local Assessment [From Baseline up to end of last cycle (approximately 48 months)]

  2. Percentage of Participants with Spleen Volume Reduction of ≥25% (SVR25) Assessed by IRC [From Baseline up to Week 48]

  3. Overall Survival (OS) [From Baseline up to 12 months after end of treatment (approximately 60 months)]

  4. Percentage of Participants with Anemia Response Assessed by International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT ) [From Baseline up to 28 Days after last dose (approximately 48 months)]

  5. Duration of Spleen Volume Reduction of ≥35% (SVR35) Assessed by IRC [From Baseline up to 28 Days after last dose (approximately 48 months)]

  6. Duration of Spleen Volume Reduction of ≥25% (SVR25) Assessed by IRC [From Baseline up to 28 Days after last dose (approximately 48 months)]

  7. Duration of Total Symptom Score is ≥50% (TSS50) Based on Local Assessment [From Baseline up to 28 Days after last dose (approximately 48 months)]

  8. Overall Response Rate (ORR) Assessed by IWG-MRT [From Baseline up to 28 Days after last dose (approximately 48 months)]

  9. Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity Grade ≥3, Serious Adverse event (SAEs), and AEs Leading to Treatment Discontinuation [From first dose of study treatment up to 30 days after end of treatment (approximately 48 months)]

  10. Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-time Curve (AUC) of Selinexor [Cycle 2 Day 1: 1, 2, 4, 6, and 24 hours post dose (each cycle is 28 days)]

  11. PK Parameter: Maximum Plasma Concentration (Cmax) of Selinexor [Cycle 2 Day 1: 1, 2, 4, 6, and 24 hours post dose (each cycle is 28 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 ≥75*10^9 per liter (/L).

  • Absolute neutrophil count (ANC) ≥1.5*10^9/L.

  • Serum direct bilirubin ≤1.5upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5ULN.

  • 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 at least 90 days after the last dose of selinexor, or for the duration as stated on the label (SmPC/USPI) for those on the comparator drug (physician's choice arm). 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 at least 90 days after the last dose of selinexor, or for the duration as stated on the label (SmPC/USPI) for those on the comparator drug (physician's choice arm). 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 or growth factors are 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.

  • Participants with contraindications to use of selinexor or all the drugs intended to be used in the comparative treatment arm.

Contacts and Locations

Locations

Site City State Country Postal Code
1 David Geffen School of Medicine at UCLA Los Angeles California United States 90095
2 The Oncology Institute of Hope and Innovation Pasadena California United States 91105
3 Rocky Mountain Cancer Centers, LLP Aurora Colorado United States 80012
4 Southeast Clinical Research Center Dalton Georgia United States 30720
5 Illinois Cancer Specialist Niles Illinois United States 60714
6 University of New Mexico CCC /NMCCA Albuquerque New Mexico United States 87131
7 Texas Oncology - Northeast Texas Tyler Texas United States 75702
8 Huntsman Cancer Institute Salt Lake City Utah United States 84112
9 Virginia Cancer Specialist Fairfax Virginia United States 22031
10 VCU Massey Cancer Center Richmond Virginia United States 23298
11 Institut de Cancéro-Hématologie Brest Bretagne France 29609
12 Sorbonne Universites - Centre De Recherche Saint Antoine (CRSA) Saint Antoine Paris France 75012
13 Centre Hospitalier Universitaire d'Angers (CHU Angers) Angers France 49933
14 Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Saint-Louis - Centre d'Investigations Cliniques (CIC) Paris France 75010
15 Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud Pierre Benite France 69495
16 University General Hospital of Patras Patras Achaia Greece 26504
17 General Hospital of Athens "EVAGGELISMOS" Athens Attiki Greece 10676
18 General Hospital of Ahens "LAIKO" Athens Attiki Greece 11526
19 South Pest Central Hospital, National Inst. Hematol. Inf. Dis. Budapest Hungary 1097
20 Pécs University Pécs Hungary 7624
21 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Forlì-Cesena Italy 47014
22 Aou Policlinico S. Orsola - UO Ematologia Bologna Italy 40138
23 Università degli Studi di Firenze - Azienda Ospedaliero - Universitaria Careggi - Dipartimento di medicina sperimentale e clinica Firenze Italy 50134
24 Azienda Unita Sanitaria Locale Latina - Ospedale Santa Maria Goretti Latina Italy 4100
25 University of Perugia Department of Medicine Hematology Section Perugia Italy 6132
26 Asst Settelaghi, Ospedale Di Circolo E Fondazione Macchi Varese Italy 21100
27 Pratia Onkologia Katowice Katowice Poland 40-519

Sponsors and Collaborators

  • Karyopharm Therapeutics Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier:
NCT04562870
Other Study ID Numbers:
  • XPORT-MF-035
  • 2020-003809-60
First Posted:
Sep 24, 2020
Last Update Posted:
Aug 15, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Karyopharm Therapeutics Inc
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 15, 2022