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

NCT ID: NCT04562870

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-17
• Study Completion Date: 2026-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 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.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Physician's Choice Treatment

Intervention Type: 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.

Interventions

Selinexor

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

Intervention Type: DRUG

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.

Intervention Type: OTHER

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), 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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Oncology Institute of Hope and Innovation

Pasadena, California, United States

Rocky Mountain Cancer Centers, LLP

Aurora, Colorado, United States

Illinois Cancer Specialist

Niles, Illinois, United States

Texas Oncology - Northeast Texas

Tyler, Texas, United States

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

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

Wuhan, Hubei, China

Affiliated Hospital of Nantong University

Nantong, Jiangsu, China

The Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Suzhou University -The First Affiliated Hospital

Suzhou, Jiangsu, China

The First Hospital of Jilin University

Changchun, Jilin, China

Sir Run Run Shaw Hospital - Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Institut de Cancéro-Hématologie

Brest, Brittany Region, France

Centre Hospitalier Universitaire d'Angers (CHU Angers)

Angers, , France

University General Hospital "ATTIKON"

Athens, Attica, Greece

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

Meldola, Forlì-Cesena, Italy

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

Florence, , Italy

Azienda Unita Sanitaria Locale Latina - Ospedale Santa Maria Goretti

Latina, , Italy

University of Perugia Department of Medicine Hematology Section

Perugia, , Italy

Asst Settelaghi, Ospedale Di Circolo E Fondazione Macchi

Varese, , Italy

Pratia Onkologia Katowice

Katowice, , Poland

Hospital Universitario 12 de Octubre

Madrid, Madrid, Spain

Countries

United States; China; France; Greece; Italy; Poland; Spain

Other Identifiers

2020-003809-60

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-513605-31-00

Identifier Type: CTIS

Identifier Source: secondary_id

XPORT-MF-035

Identifier Type: -

Identifier Source: org_study_id