Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis

NCT ID: NCT04562389

Last Updated: 2025-10-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

353 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-11

Study Completion Date

2028-03-31

Brief Summary

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This is a global, multicenter, 2-part study to evaluate the efficacy and safety of selinexor plus ruxolitinib in JAK inhibitor (JAKi) treatment-naïve myelofibrosis (MF) participants. The study will be conducted in two phases: Phase 1 (open-label) and Phase 3 (double-blind). Phase 1 (enrollment completed) was an open-label evaluation of the safety and recommended Phase 2 dose (RP2D) of selinexor in combination with ruxolitinib and included a dose escalation using a standard 3+3 design (Phase 1a) and a dose expansion part (Phase 1b). Phase 3 (ongoing), double-blind, placebo-controlled part of the study comparing the efficacy and safety of combination therapy of selinexor + ruxolitinib with combination of placebo + ruxolitinib.

Detailed Description

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Conditions

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Myelofibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Phase 1, open-label, selinexor dose escalation and expansion part (enrollment completed). Phase 3, randomized, double-blind, placebo-controlled part.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Phase 1a: Cohort 1: Selinexor 40 mg + Ruxolitinib BID

Participants with MF will receive a dose of 40 milligrams (mg) selinexor oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib twice a day (BID) based on the participants baseline platelet count.

Group Type EXPERIMENTAL

Selinexor

Intervention Type DRUG

Participants will receive a dose of 40 or 60 mg selinexor oral tablets QW.

Ruxolitinib

Intervention Type DRUG

Participants will receive a dose of 15 or 20 mg ruxolitinib oral tablets BID.

Phase 1a: Cohort 2: Selinexor 60 mg + Ruxolitinib BID

Participants with MF will receive a dose of 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Group Type EXPERIMENTAL

Selinexor

Intervention Type DRUG

Participants will receive a dose of 40 or 60 mg selinexor oral tablets QW.

Ruxolitinib

Intervention Type DRUG

Participants will receive a dose of 15 or 20 mg ruxolitinib oral tablets BID.

Phase 1b: Selinexor and Ruxolitinib BID

Participants with MF will receive a dose of 40 or 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Group Type EXPERIMENTAL

Selinexor

Intervention Type DRUG

Participants will receive a dose of 40 or 60 mg selinexor oral tablets QW.

Ruxolitinib

Intervention Type DRUG

Participants will receive a dose of 15 or 20 mg ruxolitinib oral tablets BID.

Phase 3: Selinexor 60 mg + Ruxolitinib BID

Participants with MF will receive a fixed starting dose of 60 mg selinexor (RD) oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Group Type EXPERIMENTAL

Selinexor

Intervention Type DRUG

Participants will receive a dose of 60 mg selinexor oral tablets QW.

Ruxolitinib

Intervention Type DRUG

Participants will receive a dose of 15 or 20 mg ruxolitinib oral tablets BID.

Phase 3: Placebo + Ruxolitinib BID

Participants with MF will receive a matching placebo of selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Group Type ACTIVE_COMPARATOR

Placebo

Intervention Type OTHER

Participants will receive a matching placebo of selinexor oral tablets QW

Ruxolitinib

Intervention Type DRUG

Participants will receive a dose of 15 or 20 mg ruxolitinib oral tablets BID.

Interventions

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Selinexor

Participants will receive a dose of 40 or 60 mg selinexor oral tablets QW.

Intervention Type DRUG

Selinexor

Participants will receive a dose of 60 mg selinexor oral tablets QW.

Intervention Type DRUG

Placebo

Participants will receive a matching placebo of selinexor oral tablets QW

Intervention Type OTHER

Ruxolitinib

Participants will receive a dose of 15 or 20 mg ruxolitinib oral tablets BID.

Intervention Type DRUG

Other Intervention Names

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KPT-330 KPT-330

Eligibility Criteria

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Inclusion Criteria

* Aged ≥ 18 years
* A diagnosis of primary MF or post-essential thrombocythemia (ET) or postpolycythemia- vera (PV) MF.
* Active symptoms of MF as determined by presence of at least 2 symptoms using the Myelofibrosis Symptom Assessment Form (MFSAF) V4.0.
* Participants with international prognostic scoring system (DIPSS) risk category of intermediate-1, or intermediate-2, or high-risk.
* Measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than or equal to (\>=) 450 cubic centimeter (cm\^3) .
* Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (\<=) 2.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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UAB Division of Hematology/Oncology

Birmingham, Alabama, United States

Site Status

UCLA - Satellite Site

Beverly Hills, California, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

UCLA - Satellite Site

Encino, California, United States

Site Status

City of Hope - Irvine Lennar - Satellite

Irvine, California, United States

Site Status

UCLA

Los Angles, California, United States

Site Status

The Oncology Institute of Hope & Innovation

Pasadena, California, United States

Site Status

USOR - Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, United States

Site Status

Smilow Cancer Hospital - New Haven

New Haven, Connecticut, United States

Site Status

Georgetown Lombardi Comprehensive Center

Washington D.C., District of Columbia, United States

Site Status

Norton Cancer Institute - Saint Matthews

Louisville, Kentucky, United States

Site Status

Maryland Oncology Hematology-Satellite

Annapolis, Maryland, United States

Site Status

The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status

Maryland Oncology Hematology-Satellite

Brandywine, Maryland, United States

Site Status

Maryland Oncology Hematology

Columbia, Maryland, United States

Site Status

Maryland Oncology Hematology-Satellite

Rockville, Maryland, United States

Site Status

Maryland Oncology Hematology-Satellite

Silver Spring, Maryland, United States

Site Status

The Cancer & Hematology Centers -Satellite Site

Grand Rapids, Michigan, United States

Site Status

The Cancer & Hematology Centers of Muskegon

Norton Shores, Michigan, United States

Site Status

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Mount Sinai Health System

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Duke Cancer Institue

Durham, North Carolina, United States

Site Status

USOR - Oncology Hematology Care - Kenwood

Cincinnati, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

Site Status

OhioHealth

Columbus, Ohio, United States

Site Status

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Texas Oncology

Dallas, Texas, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

USOR - Virginia Cancer Specialists - Gainesville Office

Gainesville, Virginia, United States

Site Status

VCU Massey Cancer Center

Richmond, Virginia, United States

Site Status

USOR - Virginia Oncology Associates - Virginia Beach

Virginia Beach, Virginia, United States

Site Status

Fred Hutchinson Cancer Center - SCAA South Lake Union

Seattle, Washington, United States

Site Status

West Virginia University Cancer Institute, Wheeling Hospital

Wheeling, West Virginia, United States

Site Status

University of Wisconsin - Madison

Madison, Wisconsin, United States

Site Status

Bankstown-Lidcombe Hospital

Bankstown, New South Wales, Australia

Site Status

Campbelltown Hospital

Campbelltown, New South Wales, Australia

Site Status

Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

Icon Cancer Centre - Wesley

South Brisbane, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

One Clinical Research

Nedlands, Western Australia, Australia

Site Status

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, Flemish Brabant, Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen, Belgium

Site Status

Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan

Bruges, West-Vlaanderen, Belgium

Site Status

ZNA Stuivenberg - Satelite

Antwerp, , Belgium

Site Status

ZNA Stuivenberg

Antwerp, , Belgium

Site Status

University Multiprofile Hospital for Active Treatment Sveti George - Base 1

Plovdiv, , Bulgaria

Site Status

University Multiprofile Hospital for Active Treatment Aleksandrovska

Sofia, , Bulgaria

Site Status

University Multiprofile Hospital for Active Treatment St. Ivan Rilski

Sofia, , Bulgaria

Site Status

Specialized Hospital for Active Treatment of Hematological Diseases - EAD Sofia

Sofia, , Bulgaria

Site Status

University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich

Stara Zagora, , Bulgaria

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Lakeridge Health

Oshawa, Ontario, Canada

Site Status

Research Institute of the McGill University Health Centre

Montreal, Quebec, Canada

Site Status

Vseobecna Fakultni Nemocnice v Praze

Prague, Prague, Czechia

Site Status

Fakultní Nemocnice Hradec Králové

Hradec Králové, , Czechia

Site Status

Fakultní Nemocnice Olomouc

Olomouc, , Czechia

Site Status

Aarhus Universitetshospital

Aarhus N, Central Jutland, Denmark

Site Status

Tang Severinsen, Marianne

Aalborg, North Denmark, Denmark

Site Status

Institut Bergonié

Bordeaux, Aquitaine, France

Site Status

Centre Hospitalier Universitaire Estaing

Clermont-Ferrand, Aubergne, France

Site Status

Centre Hospitalier Lyon-Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Site Status

Hôpital Morvan

Brest, Brittany Region, France

Site Status

Chu De Nîmes - Institut De Cancérologie Du Gard

Nîmes, Gard, France

Site Status

Hôpital Emile Muller

Mulhouse, Grand Est, France

Site Status

Hôpital Huriez

Lille, Hauts-de-France, France

Site Status

Hôpital Bretonneau

Tours, Indre-et-Loire, France

Site Status

Hôpital l'Archet - CHU Nice

Nice, PACA, France

Site Status

Centre Hospitalier Universitaire d'Angers

Angers, Pays de la Loire Region, France

Site Status

Centre Hospitalier Universitaire de Saint-Étienne

Saint-Priest-en-Jarez, Pays de la Loire Region, France

Site Status

Hôpital Saint-Louis

Paris, , France

Site Status

Hôpital Universitaire Pitié Salpêtrière

Paris, Île-de-France Region, France

Site Status

Hôpital Cochin

Paris, Île-de-France Region, France

Site Status

Kliniken Ostalb - Stauferklinikum Schwäbisch Gmünd

Mutlangen, Baden-Wurttemberg, Germany

Site Status

Marien Hospital Düsseldorf

Düsseldorf, North Rhine-Westphalia, Germany

Site Status

Universitätsklinikum Halle

Halle, Saxony-Anhalt, Germany

Site Status

Städtisches Krankenhaus Kiel

Kiel, Schleswig-Holstein, Germany

Site Status

Universitätsklinikum Jena

Jena, Thuringia, Germany

Site Status

Laiko General Hospital of Athens

Athens, Attica, Greece

Site Status

General Hospital of Athens "Alexandra"

Athens, Attica, Greece

Site Status

University General Hospital Attikon

Athens, Attica, Greece

Site Status

General Hospital of Thessaloniki George Papanikolaou

Thessaloniki, Central Macedonia, Greece

Site Status

University General Hospital of Ioannina

Ioánnina, Thessaly, Greece

Site Status

University General Hospital of Larissa, Hematology Department

Larissa, Thessaly, Greece

Site Status

Győr-Moson-Sopron Vármegyei Petz Aladár Egyetemi Oktató Kórház

Győr, Győr-Moson-Sopron, Hungary

Site Status

Semmelweis Egyetem

Budapest, , Hungary

Site Status

Shamir Medical Center (Assaf Harofeh)

Be’er Ya‘aqov, Central District, Israel

Site Status

The Chaim Sheba Medical Center

Ramat Gan, Central District, Israel

Site Status

Rambam Health Care Campus

Haifa, Haifa District, Israel

Site Status

Carmel Medical Center

Haifa, Haifa District, Israel

Site Status

Hadassah University Hospital - Mount Scopus - Satellite Site

Jerusalem, Jerusalem, Israel

Site Status

Hadassah University Hospital Ein Kerem

Jerusalem, Jerusalem, Israel

Site Status

Emek Medical Center

Afula, Northern District, Israel

Site Status

Western Galilee Hospital-Nahariya

Nahariya, Northern District, Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Azienda Ospedaliero Universitaria Policlinico Gaspare Rodolico - San Marco - Catania/ Presidio G. Rodolico

Catania, Catania, Italy

Site Status

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST

Meldola, Forli-Cesena, Italy

Site Status

IRCCS Ospedale Policlinico San Martino

Genova, Genoa, Italy

Site Status

Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico

Milan, Milan, Italy

Site Status

Istituto Europeo di Oncologia

Milan, Milan, Italy

Site Status

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, Milan, Italy

Site Status

Fondazione IRCCS San Gerardo dei Tintori

Monza, Monza and Brianza, Italy

Site Status

Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara

Novara, Novara, Italy

Site Status

IRCCS Centro di Riferimento Oncologico di Basilicata

Rionero in Vulture, Potenza, Italy

Site Status

Umberto I - Policlinico di Roma

Roma, Rome, Italy

Site Status

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

Torino, Turin, Italy

Site Status

Università Campus Bio-Medico di Roma

Rome, Viterbo, Italy

Site Status

Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi

Bologna, , Italy

Site Status

Azienda Ospedaliero - Universitaria Careggi

Florence, , Italy

Site Status

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Site Status

Azienda Ospedaliera Ordine Mauriziano di Torino

Torino, , Italy

Site Status

Centro Ricerche Cliniche di Verona

Verona, , Italy

Site Status

Spaarne Gasthuis - Hoofddorp

Hoofddorp, North Holland, Netherlands

Site Status

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Site Status

AIDPORT

Skórzewo, Greater Poland Voivodeship, Poland

Site Status

Medicover Integrated Clinical Services (MICS) - Centrum Medyczne Toruń

Torun, Kuyavian-Pomeranian Voivodeship, Poland

Site Status

Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku

Wroclaw, Lower Silesian Voivodeship, Poland

Site Status

Uniwersytecki Szpital Kliniczny Nr 4 w Lublinie

Lublin, Lublin Voivodeship, Poland

Site Status

Szpital Specjalistyczny w Brzozowie - Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza

Brzozów, Podkarpackie Voivodeship, Poland

Site Status

Uniwersyteckie Centrum Kliniczne w Gdańsku

Gdansk, Pomeranian Voivodeship, Poland

Site Status

Pratia Onkologia Katowice

Katowice, Silesian Voivodeship, Poland

Site Status

Specjalistyczny Szpital im. dra Alfreda Sokołowskiego w Wałbrzychu

Wałbrzych, Silesian Voivodeship, Poland

Site Status

Institutul Oncologic Prof. Dr. Ion Chiricuta

Cluj-Napoca, Cluj, Romania

Site Status

Spitalul Filantropia - Craiova

Craiova, Dolj, Romania

Site Status

Spitalul Clinic Judetean De Urgenta Târgu Mureș

Târgu Mureş, Mureș County, Romania

Site Status

Coltea - Spital Clinic

Bucharest, , Romania

Site Status

Spitalul Clinic Colentina

Bucharest, , Romania

Site Status

Institutul Regional De Oncologie Iasi

Iași, , Romania

Site Status

Pusan National University Hospital

Busan, Gwang'yeogsi, South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido, South Korea

Site Status

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, South Korea

Site Status

Kyungpook National University Hospital

Daegu, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital

Seoul, , South Korea

Site Status

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

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital San Pedro de Alcantara

Cáceres, Cáceres, Spain

Site Status

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Site Status

Hospital de Día Quirónsalud Zaragoza

Zaragoza, Zaragoza, Spain

Site Status

Institut Català d'Oncologia Badalona

Badalona, , Spain

Site Status

Hospital Universitari Vall d'Hebrón

Barcelona, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Institut Català d&#39;Oncologia Girona (ICO Girona)

Girona, , Spain

Site Status

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, , Spain

Site Status

Hospital Universitario Lucus Augusti

Lugo, , Spain

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, , Spain

Site Status

Complejo Asistencial Universitario de Salamanca - Hospital Clínico

Salamanca, , Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status

China Medical University Hospital

Taichung, Taichung, Taiwan

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Chang Gung Memorial Hospital - Kaohsiung Branch

Kaohsiung City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Chang Gung Memorial Hospital - Linkou Branch

Taoyuan District, , Taiwan

Site Status

Guy's and St Thomas' NHS Foundation Trust

London, England, United Kingdom

Site Status

Oxford University Hospitals NHS Foundation Trust

Oxford, England, United Kingdom

Site Status

United Lincolnshire Hospitals NHS Trust-Satellite Site

Boston, , United Kingdom

Site Status

United Lincolnshire Hospitals NHS Trust

Boston, , United Kingdom

Site Status

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, , United Kingdom

Site Status

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Australia Belgium Bulgaria Canada Czechia Denmark France Germany Greece Hungary Israel Italy Netherlands Poland Romania South Korea Spain Taiwan United Kingdom

References

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Mascarenhas J, Maher K, Rampal R, Bose P, Podoltsev N, Hong J, Chai Y, Kye S, Method M, Harrison C; SENTRY investigators. Selinexor plus ruxolitinib in JAK inhibitor treatment-naive myelofibrosis: SENTRY Phase 3 study design. Future Oncol. 2025 Mar;21(7):807-813. doi: 10.1080/14796694.2025.2461393. Epub 2025 Feb 6.

Reference Type DERIVED
PMID: 39911057 (View on PubMed)

Other Identifiers

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2020-003883-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506139-13-00

Identifier Type: CTIS

Identifier Source: secondary_id

XPORT-MF-034

Identifier Type: -

Identifier Source: org_study_id

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