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NCT05980806PHASE2Recruiting

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

Karyopharm Therapeutics Inc

Start Date

4/22/2024

Completion Date

10/1/2028

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.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria: * 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) Key Exclusion Criteria: * 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

Interventions

DRUG

Selinexor 60 mg

DRUG

Selinexor 40 mg

DRUG

Ruxolitinib

DRUG

Pacritinib

DRUG

Momelotinib

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Conditions

MyelofibrosisModerate ThrombocytopeniaMild Thrombocytopenia

Locations

City of Hope - Duarte Main Site

Duarte, California 91010

United States

Maryland Oncology Hematology - Independent of SCRI/ US Oncology

Columbia, Maryland 21044

United States

Weill Cornell Medicine NewYork-Presbyterian

New York, New York 10021

United States

Duke University

Durham, North Carolina 27705

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

MD Anderson

Houston, Texas 77030

United States

Huntsman Cancer Institute

Salt Lake City, Utah 84112

United States

UZ Gent

Ghent, 9000

Belgium

UZ Leuven - Campus Gasthuisberg

Leuven, 3000

Belgium

University Multiprofile Hospital for Active Treatment Sveti George - Base 1

Plovdiv, 4002

Bulgaria

University Hospital Sv.Ivan Rilski - Sofia

Sofia, 1431

Bulgaria

University Multiprofile Hospital for Active Treatment Aleksandrovska

Sofia, 1431

Bulgaria

Specialized Hospital for Active Treatment of Hematological Diseases - EAD Sofia

Sofia, 1756

Bulgaria

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

Stara Zagora, 6003

Bulgaria

Research Institute of the McGill University Health Centre

Montreal, Quebec H4A 3J1

Canada

Fakultní nemocnice Olomouc

Olomouc, 779 00

Czechia

Aarhus Universitetshospital

Aarhus N, Central Jutland 8200

Denmark

Institut Bergonié

Bordeaux, Aquitaine 33000

France

Centre Hospitalier Lyon-Sud

Pierre-Bénite, Auvergne-Rhône-Alpes 69495

France

CHU Tours, Hôpital Bretonneau Service d'Hématologie thérapie cellulaire

Tours, Indre-et-Loire 37044

France

Chu De Nîmes - Institut De Cancérologie Du Gard

Nîmes, Occitanie 30029

France

Centre Hospitalier Universitaire d'Angers

Angers, Pays de la Loire Region 49 933

France

Hôpital Saint-Louis

Paris, 75010

France

Hôpital Cochin

Paris, 75014

France

Centre Hospitalier Universitaire de Saint-Etienne

Saint-Priest-en-Jarez, 42270

France

Marien Hospital Düsseldorf

Düsseldorf, 40479

Germany

University Hospital Jena

Jena, 7747

Germany

Laiko General Hospital of Athens

Athens, Attica 11527

Greece

University General Hospital Attikon

Athens, Attica 124 62

Greece

"Georgios Papanikolaou" General Hospital of Thessaloniki

Thessaloniki, Central Macedonia 57010

Greece

University General Hospital of Ioannina, Hematology Department

Ioannina, Epirus 45500

Greece

University General Hospital of Larissa, Hematology Department

Larissa, Thessaly 41110

Greece

Semmelweis Egyetem

Budapest, 1088

Hungary

Tel Aviv Sourasky Medical Center

Tel Aviv, Tel Aviv 6423906

Israel

Rambam Health Care Campus

Haifa, 3109601

Israel

Carmel Medical Center

Haifa, 3436212

Israel

Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico

Milan, Milan 20122

Italy

Hematology Division, Mauriziano Hospital, University of Turin

Orbassano, Torino 10043

Italy

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

Torino, Turin 10126

Italy

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138

Italy

IRCCS Ospedale Policlinico San Martino

Genova, 16132

Italy

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST

Meldola,

Italy

Istituto Europeo di Oncologia

Milan, 20141

Italy

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162

Italy

Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara

Novara, 28100

Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100

Italy

Università Campus Bio-Medico di Roma

Rome, 128

Italy

Spaarne Gasthuis

Hoofddorp, 2134 TM

Netherlands

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie

Lublin, 20-954

Poland

AIDPORT

Skórzewo, 30 60-185

Poland

Medicover Clinical Integrated Systems Sp. z o.o.

Torun, 87-100

Poland

Coltea - Spital Clinic

Bucharest, 30167

Romania

Spitalul Filantropia - Craiova

Craiova, 200143

Romania

Institutul Regional de Oncologie Iasi

Iași, 700483

Romania

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

Seocho, Seoul 6591

South Korea

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi 3080

South Korea

Severance Hospital

Seoul, Seoul Teugbyeolsi 3722

South Korea

Pusan National University Hospital

Busan, 49241

South Korea

Hospital Germans Trias i Pujol

Badalona, Barcelona 8916

Spain

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Murcia 30120

Spain

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias 33011

Spain

Hospital San Pedro de Alcantara

Cáceres, 10003

Spain

Institut Català d'Oncologia Girona

Girona, 17007

Spain

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, 35010

Spain

Complejo Asistencial Universitario de Salamanca - Hospital Clínico

Salamanca, 37007

Spain

Hospital Clínico Universitario de Valencia

Valencia, 46010

Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807

Taiwan

National Taiwan University Hospital

Taipei, 100

Taiwan

Taoyuan Chang Gung Memorial Hospital

Taoyuan, 333

Taiwan

Guy's and Saint Thomas' NHS Foundation Trust

London, SE1 9RT

United Kingdom