Clinical trial NCT04562389: Study of Selinexor in Combination with Ruxolitinib in Myelofibrosis
Official title: A Phase 1/3 Study to Evaluate Efficacy and Safety of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination with Ruxolitinib in Treatment-naïve Patients with Myelofibrosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Myelofibrosis
Keywords: Myelofibrosis
Selinexor
Ruxolitinib
Janus kinase 2
Myeloproliferative neoplasms
Lead sponsor: Karyopharm Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2020-09-24
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1, open-label, selinexor dose escalation and expansion part (enrollment completed). Phase 3, randomized, double-blind, placebo-controlled part.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: At Week 24
measure: 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
timeFrame: At Week 24
measure: Phase 1: Maximum Tolerated Dose (MTD)
timeFrame: Approximately within the first cycle (28 days) of therapy
measure: Phase 1: Recommended Phase 2 Dose (RP2D)
timeFrame: Approximately within the first cycle (28 days) of therapy
measure: Phase 1: Number of Participants With Adverse Events (AEs) by Occurrence, Nature, and Severity
timeFrame: From start of drug administration up to 30 days after last dose of study treatment (approximately 48 months)
Secondary outcomes:
measure: Phase 3: Overall survival (OS)
timeFrame: From Baseline up to EoS (approximately 48 months)
measure: Phase 3: Progression-free survival (PFS)
timeFrame: Time from randomization until disease progression or death, whichever occurs first (approximately 48 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Division of Hematology/Oncology
state: Alabama
city: Beverly Hills
country: United States
facility: UCLA - Satellite Site
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Encino
country: United States
facility: UCLA - Satellite Site
state: California
city: Irvine
country: United States
facility: City of Hope - Irvine Lennar - Satellite
state: California
city: Los Angles
country: United States
facility: UCLA
state: California
city: Pasadena
country: United States
facility: The Oncology Institute of Hope & Innovation
state: California
city: Aurora
country: United States
facility: USOR - Rocky Mountain Cancer Centers - Aurora
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital - New Haven
state: Connecticut
city: Louisville
country: United States
facility: Norton Cancer Institute - Saint Matthews
state: Kentucky
city: Annapolis
country: United States
facility: Maryland Oncology Hematology-Satellite
state: Maryland
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Brandywine
country: United States
facility: Maryland Oncology Hematology-Satellite
state: Maryland
city: Columbia
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology-Satellite
state: Maryland
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology-Satellite
state: Maryland
city: Grand Rapids
country: United States
facility: The Cancer & Hematology Centers -Satellite Site
state: Michigan
city: Norton Shores
country: United States
facility: The Cancer & Hematology Centers of Muskegon
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Health System
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Institue
state: North Carolina
city: Cincinnati
country: United States
facility: USOR - Oncology Hematology Care - Kenwood
state: Ohio
city: Columbus
country: United States
facility: OhioHealth
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Gainesville
country: United States
facility: USOR - Virginia Cancer Specialists - Gainesville Office
state: Virginia
city: Richmond
country: United States
facility: VCU Massey Cancer Center
state: Virginia
city: Virginia Beach
country: United States
facility: USOR - Virginia Oncology Associates - Virginia Beach
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center - SCAA South Lake Union
state: Washington
city: Wheeling
country: United States
facility: West Virginia University Cancer Institute, Wheeling Hospital
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
state: Flemish Brabant
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-Vlaanderen
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
state: West-Vlaanderen
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg - Satelite
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sveti George - Base 1
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Aleksandrovska
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment St. Ivan Rilski
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Hematological Diseases - EAD Sofia
city: Stara Zagora
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Montreal
country: Canada
facility: Research Institute of the McGill University Health Centre
state: Quebec
city: Praha 2
country: Czech Republic
facility: Vseobecna Fakultni Nemocnice v Praze
state: Prague
city: Hradec Králové
country: Czechia
facility: Fakultní Nemocnice Hradec Králové
city: Olomouc
country: Czechia
facility: Fakultní Nemocnice Olomouc
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital
state: Midtjylland
city: Aalborg
country: Denmark
facility: Tang Severinsen, Marianne
state: Nordjylland
city: Bordeaux
country: France
facility: Institut Bergonié
state: Aquitaine
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire Estaing
state: Aubergne
city: Brest
country: France
facility: Hôpital Morvan
state: Bretagne
city: Nimes
country: France
facility: Chu De Nîmes - Institut De Cancérologie Du Gard
state: Gard
city: Mulhouse
country: France
facility: Hôpital Emile Muller
state: Grand Est
city: Lille
country: France
facility: Hôpital Huriez
state: Hauts-de-France
city: Paris
country: France
facility: Hôpital Universitaire Pitié Salpêtrière
state: Ile-de-France
city: Tours Cedex
country: France
facility: Hôpital Bretonneau
state: Indre-et-Loire
city: Saint-Priest-en-Jarez
country: France
facility: Centre Hospitalier Universitaire de Saint-Étienne
state: Loire
city: Nice Cedex 3
country: France
facility: Hôpital l'Archet - CHU Nice
state: Paca
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
state: Pays de la Loire
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon-Sud
state: Rhone-Alpes
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Mutlangen
country: Germany
facility: Kliniken Ostalb - Stauferklinikum Schwäbisch Gmünd
state: Baden-Württemberg
city: Düsseldorf
country: Germany
facility: Marien Hospital Düsseldorf
state: Nordrhein-Westfalen
city: Halle
country: Germany
facility: Universitätsklinikum Halle
state: Sachsen-Anhalt
city: Kiel
country: Germany
facility: Städtisches Krankenhaus Kiel
state: Schleswig-Holstein
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thuringen
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
state: Attica
city: Athens
country: Greece
facility: University General Hospital Attikon
state: Attica
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki George Papanikolaou
state: Central Macedonia
city: Larissa
country: Greece
facility: University General Hospital of Larissa, Hematology Department
state: Thessaly
city: Győr
country: Hungary
facility: Győr-Moson-Sopron Vármegyei Petz Aladár Egyetemi Oktató Kórház
state: Gyor-Moson-Sopron
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Be'er Ya'akov
country: Israel
facility: Shamir Medical Center (Assaf Harofeh)
state: Central District
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
state: Central District
city: Haifa
country: Israel
facility: Rambam Health Care Campus
state: Haifa District
city: Haifa
country: Israel
facility: Carmel Medical Center
state: Haifa District
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Mount Scopus - Satellite Site
state: Jerusalem District
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
state: Jerusalem District
city: Afula
country: Israel
facility: Emek Medical Center
state: Northern District
city: Nahariya
country: Israel
facility: Western Galilee Hospital-Nahariya
state: Northern District
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
state: Forli-Cesena
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
state: Genoa
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico
state: Milan
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: Milan
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
state: Milan
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
state: Monza and Brianza
city: Rionero In Vulture
country: Italy
facility: IRCCS Centro di Riferimento Oncologico di Basilicata
state: Potenza
city: Torino
country: Italy
facility: Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino
state: Turin
city: Rome
country: Italy
facility: Università Campus Bio-Medico di Roma
state: Viterbo
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi
city: Firenze
country: Italy
facility: Azienda Ospedaliero - Universitaria Careggi
city: Novara
country: Italy
facility: Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano di Torino
city: Verona
country: Italy
facility: Centro Ricerche Cliniche di Verona
city: Busan Gwang'yeogsi [Pusan-Kwangyokshi]
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Hwasun-gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seongnam-si Gyeonggido [Kyonggi-do]
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea - Seoul St. Mary's Hospital
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Wrocław
country: Poland
facility: Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
state: Dolnoslaskie
city: Toruń
country: Poland
facility: Medicover Integrated Clinical Services (MICS) - Centrum Medyczne Toruń
state: Kujawsko-Pomorskie
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Kliniczny Nr 4 w Lublinie
state: Lubelskie
city: Brzozów
country: Poland
facility: Szpital Specjalistyczny w Brzozowie - Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza
state: Podkarpackie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne w Gdańsku
state: Pomorskie
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
state: Slaskie
city: Wałbrzych
country: Poland
facility: Specjalistyczny Szpital im. dra Alfreda Sokołowskiego w Wałbrzychu
state: Slaskie
city: Skórzewo
country: Poland
facility: AIDPORT
state: Wielkopolskie
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic Prof. Dr. Ion Chiricuta
state: Cluj
city: Craiova
country: Romania
facility: Spitalul Filantropia - Craiova
state: Dolj
city: Moldova
country: Romania
facility: Institutul Regional De Oncologie Iasi
state: Iasi
city: Târgu Mureş
country: Romania
facility: Spitalul Clinic Judetean De Urgenta Târgu Mureș
state: Mureș
city: Bucuresti
country: Romania
facility: Coltea - Spital Clinic
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: Institut Català d'Oncologia Badalona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Girona
country: Spain
facility: Institut Català d&#39;Oncologia Girona (ICO Girona)
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrin
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Murcia
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - Hospital Clínico
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Taichung City
country: Taiwan
facility: China Medical University Hospital
state: Taichung
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital - Kaohsiung Branch
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou Branch
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
state: England
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
state: England
city: Boston
country: United Kingdom
facility: United Lincolnshire Hospitals NHS Trust-Satellite Site
city: Boston
country: United Kingdom
facility: United Lincolnshire Hospitals NHS Trust
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Study officials:
References: