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

NCT05980806 | Recruiting Phase 2 FDA Drug

• 1 other identifier: XPORT-MF-044
• Study Type: interventional
• Target: 58
• Locations: 19 countries
• Sites: 70

Brief Summary

The main purpose of this study is to evaluate the efficacy of selinexor in JAKi-naïve participants with myelofibrosis (MF) and with normal platelet counts or with mild to moderate thrombocytopenia based on spleen volume reduction (SVR). Additional efficacy and safety parameters will also be assessed during the study.

Conditions

Myelofibrosis; Moderate Thrombocytopenia; Mild Thrombocytopenia

Keywords

Myelofibrosis; Selinexor; Total Symptom Score; Myelofibrosis Symptom Assessment Form; Spleen Volume Reduction; TSS50; SVR35; JAK2; KPT-330; Pacritinib; Ruxolitinib; Momelotinib; Thrombocytopenia; Abs-TSS

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants with Spleen Volume Reduction ≥35% (SVR35) at Week 24

  Measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) Scan by Investigator assessment.

  At Week 24

Secondary Outcomes (2)

• Absolute Mean Change in Total Symptom Score (Abs-TSS) from baseline to Week 24

  At Baseline and Week 24

• Incidence and severity of TEAEs, including TRAEs and SAEs

  From Baseline to EoS (approximately 48 months)

Study Arms (2)

Selinexor 60 mg (Arm 1)

EXPERIMENTAL

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. Optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values at Week 12 or Week 24 of treatment.

Drug: Selinexor 60 mg; Drug: Ruxolitinib; Drug: Pacritinib; Drug: Momelotinib

Selinexor 40 mg (Arm 2)

EXPERIMENTAL

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. Optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values at Week 12 or Week 24 of treatment.

Drug: Selinexor 40 mg; Drug: Ruxolitinib; Drug: Pacritinib; Drug: Momelotinib

Interventions

Selinexor 60 mg DRUG

Participants will receive selinexor 60 mg oral tablets QW.

Also known as: KPT-330

Selinexor 60 mg (Arm 1)

Selinexor 40 mg DRUG

Participants will receive selinexor 40 mg oral tablets QW.

Also known as: KPT-330

Selinexor 40 mg (Arm 2)

Ruxolitinib DRUG

Participants will receive ruxolitinib per local package insert.

Also known as: JAKAFI

Selinexor 40 mg (Arm 2); Selinexor 60 mg (Arm 1)

Pacritinib DRUG

Participants will receive pacritinib per local package insert. For countries where not approved, 200 mg twice daily is the starting dose.

Also known as: VONJO

Selinexor 40 mg (Arm 2); Selinexor 60 mg (Arm 1)

Momelotinib DRUG

Participants will receive momelotinib per local package insert.

Also known as: OJJAARA

Selinexor 40 mg (Arm 2); Selinexor 60 mg (Arm 1)

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 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 or 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 C1D1 are acceptable)
• 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 greater than or equal to (\>=) 50 x 10\^9/L without platelet transfusion within 7 days prior to the first dose of selinexor
• Absolute neutrophil count (ANC) \>=1.0 × 10\^9/L without need for growth factors within 7 days prior to the first dose of selinexor
• Adequate liver function as defined by the following: aspartate transaminase (AST) and alanine transaminase (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 an average score \>= 5 or total score of \>= 12 at screening (at least 5 of 7 consecutive days immediately preceding C1D1) using the MFSAF V4.0
• Must provide bone marrow biopsy samples (samples obtained up to 3 months prior to C1D1 are permitted) at screening and during the study
• Currently not eligible for stem cell transplantation
• Must be willing to complete the MFSAF V4.0 daily during the study for evaluating the symptom response (i.e., TSS50)

You may not qualify if:

• 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
• Females who are pregnant or lactating
• Prior splenectomy, splenic radiation, or a splenic embolization within 6 months prior to C1D1
• History of myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG), cerebrovascular accident (transient ischemic attack \[TIA\]), ventricular arrhythmias, congestive heart failure class \> 2 per New York Heart Association (NYHA) within 6 months of C1D1
• Unable to tolerate two forms of antiemetics prior to each dose for the first two cycles

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (70)

City of Hope - Duarte Main Site

Duarte, California, 91010, United States

RECRUITING

Maryland Oncology Hematology - Independent of SCRI/ US Oncology

Columbia, Maryland, 21044, United States

RECRUITING

Weill Cornell Medicine NewYork-Presbyterian

New York, New York, 10021, United States

RECRUITING

Duke University

Durham, North Carolina, 27705, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

MD Anderson

Houston, Texas, 77030, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

UZ Gent

Ghent, 9000, Belgium

RECRUITING

UZ Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

RECRUITING

University Multiprofile Hospital for Active Treatment Sveti George - Base 1

Plovdiv, 4002, Bulgaria

RECRUITING

University Hospital Sv.Ivan Rilski - Sofia

Sofia, 1431, Bulgaria

RECRUITING

University Multiprofile Hospital for Active Treatment Aleksandrovska

Sofia, 1431, Bulgaria

RECRUITING

Specialized Hospital for Active Treatment of Hematological Diseases - EAD Sofia

Sofia, 1756, Bulgaria

RECRUITING

University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD Department of Clinical Hematology

Stara Zagora, 6003, Bulgaria

RECRUITING

Research Institute of the McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Fakultní nemocnice Olomouc

Olomouc, 779 00, Czechia

RECRUITING

Aarhus Universitetshospital

Aarhus N, Central Jutland, 8200, Denmark

RECRUITING

Institut Bergonié

Bordeaux, Aquitaine, 33000, France

RECRUITING

Centre Hospitalier Lyon-Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France

RECRUITING

CHU Tours, Hôpital Bretonneau Service d'Hématologie thérapie cellulaire

Tours, Indre-et-Loire, 37044, France

RECRUITING

Chu De Nîmes - Institut De Cancérologie Du Gard

Nîmes, Occitanie, 30029, France

RECRUITING

Centre Hospitalier Universitaire d'Angers

Angers, Pays de la Loire Region, 49 933, France

RECRUITING

Hôpital Saint-Louis

Paris, 75010, France

RECRUITING

Hôpital Cochin

Paris, 75014, France

RECRUITING

Centre Hospitalier Universitaire de Saint-Etienne

Saint-Priest-en-Jarez, 42270, France

RECRUITING

Marien Hospital Düsseldorf

Düsseldorf, 40479, Germany

RECRUITING

University Hospital Jena

Jena, 7747, Germany

RECRUITING

Laiko General Hospital of Athens

Athens, Attica, 11527, Greece

RECRUITING

University General Hospital Attikon

Athens, Attica, 124 62, Greece

RECRUITING

"Georgios Papanikolaou" General Hospital of Thessaloniki

Thessaloniki, Central Macedonia, 57010, Greece

RECRUITING

University General Hospital of Ioannina, Hematology Department

Ioannina, Epirus, 45500, Greece

RECRUITING

University General Hospital of Larissa, Hematology Department

Larissa, Thessaly, 41110, Greece

RECRUITING

Semmelweis Egyetem

Budapest, 1088, Hungary

RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, Tel Aviv, 6423906, Israel

RECRUITING

Rambam Health Care Campus

Haifa, 3109601, Israel

RECRUITING

Carmel Medical Center

Haifa, 3436212, Israel

RECRUITING

Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico

Milan, Milan, 20122, Italy

RECRUITING

Hematology Division, Mauriziano Hospital, University of Turin

Orbassano, Torino, 10043, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino

Torino, Turin, 10126, Italy

RECRUITING

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, 16132, Italy

RECRUITING

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST

Meldola, Italy

RECRUITING

Istituto Europeo di Oncologia

Milan, 20141, Italy

RECRUITING

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara

Novara, 28100, Italy

RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

RECRUITING

Università Campus Bio-Medico di Roma

Rome, 128, Italy

RECRUITING

Spaarne Gasthuis

Hoofddorp, 2134 TM, Netherlands

RECRUITING

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie

Lublin, 20-954, Poland

RECRUITING

AIDPORT

Skórzewo, 30 60-185, Poland

RECRUITING

Medicover Clinical Integrated Systems Sp. z o.o.

Torun, 87-100, Poland

RECRUITING

Coltea - Spital Clinic

Bucharest, 30167, Romania

RECRUITING

Spitalul Filantropia - Craiova

Craiova, 200143, Romania

RECRUITING

Institutul Regional de Oncologie Iasi

Iași, 700483, Romania

RECRUITING

Seoul St. Mary's Hospital, The Catholic University of Korea

Seocho, Seoul, 6591, South Korea

RECRUITING

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi, 3080, South Korea

RECRUITING

Severance Hospital

Seoul, Seoul Teugbyeolsi, 3722, South Korea

RECRUITING

Pusan National University Hospital

Busan, 49241, South Korea

RECRUITING

Hospital Germans Trias i Pujol

Badalona, Barcelona, 8916, Spain

RECRUITING

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

RECRUITING

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

RECRUITING

Institut Català d'Oncologia Girona

Girona, 17007, Spain

RECRUITING

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, 35010, Spain

RECRUITING

Complejo Asistencial Universitario de Salamanca - Hospital Clínico

Salamanca, 37007, Spain

RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

Taoyuan Chang Gung Memorial Hospital

Taoyuan District, 333, Taiwan

RECRUITING

Guy's and Saint Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis; Thrombocytopenia

Interventions

selinexor; ruxolitinib; 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Platelet Disorders; Cytopenia

Central Study Contacts

Karyopharm Medical Information

CONTACT

(888) 209-9326; clinicaltrials@karyopharm.com

Study Design

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

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 8, 2023
• Study Start: April 22, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

IT (11); HU (1); KR (4); BU (5); TW (3); DK (1); PL (3); GB (1); DE (2); IL (3); CZ (1); RO (3); NL (1); GR (5); BE (2); FR (8); ES (8); US (7); CA (1)