Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis
- Registration Number
- NCT04562389
- Lead Sponsor
- Karyopharm Therapeutics Inc
- Brief Summary
This is a global, multicenter Phase 1/3 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 dose (RD) 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). In Phase 3, JAKi treatment-naïve MF participants are enrolled in 2:1 ratio to receive the combination therapy of selinexor + ruxolitinib or the combination of placebo + ruxolitinib.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 350
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1a: Cohort 2: Selinexor 60 mg + Ruxolitinib BID Selinexor 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. Phase 3: Placebo + Ruxolitinib BID Placebo 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. Phase 1a: Cohort 1: Selinexor 40 mg + Ruxolitinib BID Selinexor 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. Phase 1a: Cohort 2: Selinexor 60 mg + Ruxolitinib BID Ruxolitinib 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. Phase 1a: Cohort 1: Selinexor 40 mg + Ruxolitinib BID Ruxolitinib 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. Phase 1b: Selinexor and Ruxolitinib BID Selinexor 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. Phase 1b: Selinexor and Ruxolitinib BID Ruxolitinib 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. Phase 3: Selinexor 60 mg + Ruxolitinib BID Selinexor 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. Phase 3: Selinexor 60 mg + Ruxolitinib BID Ruxolitinib 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. Phase 3: Placebo + Ruxolitinib BID Ruxolitinib 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.
- Primary Outcome Measures
Name Time Method Phase 3: Proportion of Participants with Spleen Volume Reduction (SVR) of Greater than or Equal to (>=) 35 Percent (%) (SVR35) at Week 24 Measured by the Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) Scan At Week 24 Phase 3: Absolute mean change in TSS (Abs-TSS) from baseline to Week 24 as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 At Week 24 Phase 1: Maximum Tolerated Dose (MTD) Approximately within the first cycle (28 days) of therapy Phase 1: Recommended Phase 2 Dose (RP2D) Approximately within the first cycle (28 days) of therapy Phase 1: Number of Participants With Adverse Events (AEs) by Occurrence, Nature, and Severity From start of drug administration up to 30 days after last dose of study treatment (approximately 48 months)
- Secondary Outcome Measures
Name Time Method Phase 3: Overall survival (OS) From Baseline up to EoS (approximately 48 months) Phase 3: Progression-free survival (PFS) Time from randomization until disease progression or death, whichever occurs first (approximately 48 months)
Trial Locations
- Locations (145)
UAB Division of Hematology/Oncology
🇺🇸Birmingham, Alabama, United States
UCLA - Satellite Site
🇺🇸Encino, California, United States
City of Hope
🇺🇸Duarte, California, United States
City of Hope - Irvine Lennar - Satellite
🇺🇸Irvine, California, United States
UCLA
🇺🇸Los Angles, California, United States
The Oncology Institute of Hope & Innovation
🇺🇸Pasadena, California, United States
USOR - Rocky Mountain Cancer Centers - Aurora
🇺🇸Aurora, Colorado, United States
Smilow Cancer Hospital - New Haven
🇺🇸New Haven, Connecticut, United States
Norton Cancer Institute - Saint Matthews
🇺🇸Louisville, Kentucky, United States
Maryland Oncology Hematology-Satellite
🇺🇸Silver Spring, Maryland, United States
The Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Maryland Oncology Hematology
🇺🇸Columbia, Maryland, United States
The Cancer & Hematology Centers -Satellite Site
🇺🇸Grand Rapids, Michigan, United States
The Cancer & Hematology Centers of Muskegon
🇺🇸Norton Shores, Michigan, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Mount Sinai Health System
🇺🇸New York, New York, United States
University Multiprofile Hospital for Active Treatment St. Ivan Rilski
🇧🇬Sofia, Bulgaria
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke Cancer Institue
🇺🇸Durham, North Carolina, United States
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
USOR - Oncology Hematology Care - Kenwood
🇺🇸Cincinnati, Ohio, United States
OhioHealth
🇺🇸Columbus, Ohio, United States
Vanderbilt Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Texas Oncology
🇺🇸Dallas, Texas, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
USOR - Virginia Cancer Specialists - Gainesville Office
🇺🇸Gainesville, Virginia, United States
VCU Massey Cancer Center
🇺🇸Richmond, Virginia, United States
USOR - Virginia Oncology Associates - Virginia Beach
🇺🇸Virginia Beach, Virginia, United States
Fred Hutchinson Cancer Center - SCAA South Lake Union
🇺🇸Seattle, Washington, United States
West Virginia University Cancer Institute, Wheeling Hospital
🇺🇸Wheeling, West Virginia, United States
University of Wisconsin - Madison
🇺🇸Madison, Wisconsin, United States
Universitair Ziekenhuis Leuven - Campus Gasthuisberg
🇧🇪Leuven, Flemish Brabant, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Oost-Vlaanderen, Belgium
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
🇧🇪Brugge, West-Vlaanderen, Belgium
ZNA Stuivenberg - Satelite
🇧🇪Antwerpen, Belgium
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
University Multiprofile Hospital for Active Treatment Sveti George - Base 1
🇧🇬Plovdiv, Bulgaria
University Multiprofile Hospital for Active Treatment Aleksandrovska
🇧🇬Sofia, Bulgaria
Specialized Hospital for Active Treatment of Hematological Diseases - EAD Sofia
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich
🇧🇬Stara Zagora, Bulgaria
Research Institute of the McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Vseobecna Fakultni Nemocnice v Praze
🇨🇿Praha 2, Prague, Czech Republic
Fakultní Nemocnice Hradec Králové
🇨🇿Hradec Králové, Czechia
Fakultní Nemocnice Olomouc
🇨🇿Olomouc, Czechia
Aarhus Universitetshospital
🇩🇰Aarhus N, Midtjylland, Denmark
Tang Severinsen, Marianne
🇩🇰Aalborg, Nordjylland, Denmark
Institut Bergonié
🇫🇷Bordeaux, Aquitaine, France
Centre Hospitalier Universitaire Estaing
🇫🇷Clermont-Ferrand, Aubergne, France
Hôpital Morvan
🇫🇷Brest, Bretagne, France
Chu De Nîmes - Institut De Cancérologie Du Gard
🇫🇷Nimes, Gard, France
Hôpital Emile Muller
🇫🇷Mulhouse, Grand Est, France
Hôpital Huriez
🇫🇷Lille, Hauts-de-France, France
Hôpital Universitaire Pitié Salpêtrière
🇫🇷Paris, Ile-de-France, France
Hôpital Bretonneau
🇫🇷Tours Cedex, Indre-et-Loire, France
Centre Hospitalier Universitaire de Saint-Étienne
🇫🇷Saint-Priest-en-Jarez, Loire, France
Hôpital l'Archet - CHU Nice
🇫🇷Nice Cedex 3, Paca, France
Centre Hospitalier Universitaire d'Angers
🇫🇷Angers, Pays de la Loire, France
Centre Hospitalier Lyon-Sud
🇫🇷Pierre-Bénite, Rhone-Alpes, France
Hôpital Saint-Louis
🇫🇷Paris, France
Kliniken Ostalb - Stauferklinikum Schwäbisch Gmünd
🇩🇪Mutlangen, Baden-Württemberg, Germany
Marien Hospital Düsseldorf
🇩🇪Düsseldorf, Nordrhein-Westfalen, Germany
Universitätsklinikum Halle
🇩🇪Halle, Sachsen-Anhalt, Germany
Städtisches Krankenhaus Kiel
🇩🇪Kiel, Schleswig-Holstein, Germany
Universitätsklinikum Jena
🇩🇪Jena, Thuringen, Germany
Laiko General Hospital of Athens
🇬🇷Athens, Attica, Greece
University General Hospital Attikon
🇬🇷Athens, Attica, Greece
General Hospital of Thessaloniki George Papanikolaou
🇬🇷Thessaloniki, Central Macedonia, Greece
University General Hospital of Larissa, Hematology Department
🇬🇷Larissa, Thessaly, Greece
Győr-Moson-Sopron Vármegyei Petz Aladár Egyetemi Oktató Kórház
🇭🇺Győr, Gyor-Moson-Sopron, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Shamir Medical Center (Assaf Harofeh)
🇮🇱Be'er Ya'akov, Central District, Israel
The Chaim Sheba Medical Center
🇮🇱Ramat Gan, Central District, Israel
Rambam Health Care Campus
🇮🇱Haifa, Haifa District, Israel
Carmel Medical Center
🇮🇱Haifa, Haifa District, Israel
Hadassah University Hospital - Mount Scopus - Satellite Site
🇮🇱Jerusalem, Jerusalem District, Israel
Hadassah University Hospital Ein Kerem
🇮🇱Jerusalem, Jerusalem District, Israel
Emek Medical Center
🇮🇱Afula, Northern District, Israel
Western Galilee Hospital-Nahariya
🇮🇱Nahariya, Northern District, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
🇮🇹Meldola, Forli-Cesena, Italy
IRCCS Ospedale Policlinico San Martino
🇮🇹Genova, Genoa, Italy
Hospital Universitario Lucus Augusti
🇪🇸Lugo, Spain
Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico
🇮🇹Milano, Milan, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Milan, Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Milan, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, Monza and Brianza, Italy
IRCCS Centro di Riferimento Oncologico di Basilicata
🇮🇹Rionero In Vulture, Potenza, Italy
Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino
🇮🇹Torino, Turin, Italy
Università Campus Bio-Medico di Roma
🇮🇹Rome, Viterbo, Italy
Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi
🇮🇹Bologna, Italy
Azienda Ospedaliero - Universitaria Careggi
🇮🇹Firenze, Italy
Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
🇮🇹Novara, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Italy
Azienda Ospedaliera Ordine Mauriziano di Torino
🇮🇹Torino, Italy
Centro Ricerche Cliniche di Verona
🇮🇹Verona, Italy
Pusan National University Hospital
🇰🇷Busan Gwang'yeogsi [Pusan-Kwangyokshi], Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun-gun, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si Gyeonggido [Kyonggi-do], Korea, Republic of
Samsung Medical Center
🇰🇷Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea - Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
🇵🇱Wrocław, Dolnoslaskie, Poland
Medicover Integrated Clinical Services (MICS) - Centrum Medyczne Toruń
🇵🇱Toruń, Kujawsko-Pomorskie, Poland
Uniwersytecki Szpital Kliniczny Nr 4 w Lublinie
🇵🇱Lublin, Lubelskie, Poland
Szpital Specjalistyczny w Brzozowie - Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza
🇵🇱Brzozów, Podkarpackie, Poland
Uniwersyteckie Centrum Kliniczne w Gdańsku
🇵🇱Gdańsk, Pomorskie, Poland
Pratia Onkologia Katowice
🇵🇱Katowice, Slaskie, Poland
Specjalistyczny Szpital im. dra Alfreda Sokołowskiego w Wałbrzychu
🇵🇱Wałbrzych, Slaskie, Poland
AIDPORT
🇵🇱Skórzewo, Wielkopolskie, Poland
Institutul Oncologic Prof. Dr. Ion Chiricuta
🇷🇴Cluj-Napoca, Cluj, Romania
Spitalul Filantropia - Craiova
🇷🇴Craiova, Dolj, Romania
Institutul Regional De Oncologie Iasi
🇷🇴Moldova, Iasi, Romania
Spitalul Clinic Judetean De Urgenta Târgu Mureș
🇷🇴Târgu Mureş, Mureș, Romania
Coltea - Spital Clinic
🇷🇴Bucuresti, Romania
Spitalul Clinic Colentina
🇷🇴Bucuresti, Romania
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Institut Català d'Oncologia Badalona
🇪🇸Badalona, Spain
Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Institut Català d'Oncologia Girona (ICO Girona)
🇪🇸Girona, Spain
Hospital Universitario de Gran Canaria Doctor Negrin
🇪🇸Las Palmas de Gran Canaria, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Complejo Asistencial Universitario de Salamanca - Hospital Clínico
🇪🇸Salamanca, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
China Medical University Hospital
🇨🇳Taichung City, Taichung, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Chang Gung Memorial Hospital - Kaohsiung Branch
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Chang Gung Memorial Hospital - Linkou Branch
🇨🇳Taoyuan, Taiwan
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, England, United Kingdom
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, England, United Kingdom
United Lincolnshire Hospitals NHS Trust-Satellite Site
🇬🇧Boston, United Kingdom
United Lincolnshire Hospitals NHS Trust
🇬🇧Boston, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle Upon Tyne, United Kingdom