A Study to Evaluate Single Agent Selinexor Versus Physician's Choice in Participants With Previously Treated Myelofibrosis

NCT04562870 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: XPORT-MF-0352020-003809-602024-513605-31-00
• Study Type: interventional
• Target: 112
• Locations: 7 countries
• Sites: 21

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.

Conditions

Myelofibrosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with Spleen Volume Reduction of Greater Than or Equal to (≥) 35 Percent (%) (SVR35)

  From Baseline up to Week 24

Secondary Outcomes (11)

• 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 Week 24

• Percentage of Participants with Spleen Volume Reduction of ≥25% (SVR25)

  From Baseline up to Week 24

• Overall Survival (OS)

  From Baseline up to 12 months after end of treatment (approximately 48 months)]

• 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)

• Duration of Spleen Volume Reduction of ≥35% (SVR35)

  From Baseline up to Week 24

Study Arms (2)

Arm S: Selinexor

EXPERIMENTAL

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 for first 2 cycles followed by selinexor 60 mg once weekly (QW) in subsequent cycles orally on Days 1, 8, 15, and 22 of each 28-day cycle to participants on Arm S.

Drug: Selinexor

Arm PC: Physician's Choice Treatment

ACTIVE COMPARATOR

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

Interventions

Selinexor DRUG

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

Arm S: Selinexor

Physician's Choice Treatment OTHER

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.

Arm PC: Physician's Choice Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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), 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 ≤1.5\*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.

You may not qualify if:

• \>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.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (21)

The Oncology Institute of Hope and Innovation

Pasadena, California, 91105, United States

Location

Rocky Mountain Cancer Centers, LLP

Aurora, Colorado, 80012, United States

Location

Illinois Cancer Specialist

Niles, Illinois, 60714, United States

Location

Texas Oncology - Northeast Texas

Tyler, Texas, 75702, United States

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Affiliated Hospital of Nantong University

Nantong, Jiangsu, 226001, China

Location

The Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215004, China

Location

Suzhou University -The First Affiliated Hospital

Suzhou, Jiangsu, 215007, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Sir Run Run Shaw Hospital - Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

Location

Institut de Cancéro-Hématologie

Brest, Brittany Region, 29609, France

Location

Centre Hospitalier Universitaire d'Angers (CHU Angers)

Angers, 49933, France

Location

University General Hospital "ATTIKON"

Athens, Attica, 12462, Greece

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS

Meldola, Forlì-Cesena, 47014, Italy

Location

Università degli Studi di Firenze - Azienda Ospedaliero - Universitaria Careggi - Dipartimento di medicina sperimentale e clinica

Florence, 50134, Italy

Location

Azienda Unita Sanitaria Locale Latina - Ospedale Santa Maria Goretti

Latina, 4100, Italy

Location

University of Perugia Department of Medicine Hematology Section

Perugia, 6132, Italy

Location

Asst Settelaghi, Ospedale Di Circolo E Fondazione Macchi

Varese, 21100, Italy

Location

Pratia Onkologia Katowice

Katowice, 40-519, Poland

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

selinexor

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: September 24, 2020
• Study Start: March 17, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: October 3, 2025

Record last verified: 2025-09

Locations

US (4); FR (2); PL (1); IT (5); ES (1); GR (1); CN (7)