Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)
- Conditions
- MyelofibrosisPrimary MyelofibrosisPost-polycythemia Vera MyelofibrosisPost-essential Thrombocythemia Myelofibrosis
- Interventions
- Registration Number
- NCT04603495
- Lead Sponsor
- Constellation Pharmaceuticals
- Brief Summary
A Phase 3, randomized, blinded study comparing pelabresib (CPI-0610) and ruxolitinib with placebo and ruxolitinib in myelofibrosis (MF) patients that have not been previously treated with Janus kinase inhibitors (JAKi). Pelabresib is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 430
- Aged ≥ 18 years
- Confirmed diagnosis of myelofibrosis (primary, post-polycythemia vera, or post essential thrombocythemia)
- Adequate hematologic, renal, and hepatic function
- Have at least 2 symptoms with an average score ≥ 3 or an average total score of ≥ 10 over the 7-day period prior to randomization using the MFSAF v4.0
- Prognostic risk-factor score of Intermediate-1 or higher per Dynamic International Prognostic Scoring System (DIPSS) scoring system
- Spleen volume of ≥ 450 cm^3
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Splenectomy or splenic irradiation in the previous 6 months
- Chronic or active conditions and/or concomitant medication use that would prohibit treatment
- Had prior treatment with any JAKi or BET inhibitor for treatment of a myeloproliferative neoplasm
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pelabresib + ruxolitinib Pelabresib Pelabresib monohydrate tablets + ruxolitinib phosphate tablets Pelabresib + ruxolitinib Ruxolitinib Pelabresib monohydrate tablets + ruxolitinib phosphate tablets Placebo + ruxolitinib Ruxolitinib Matching placebo tablets + ruxolitinib phosphate tablets Placebo + ruxolitinib Placebo Matching placebo tablets + ruxolitinib phosphate tablets
- Primary Outcome Measures
Name Time Method Number of Participants With Splenic Response by Central Reads at Week 24 24 weeks of treatment The primary endpoint of the study is splenic response, defined as a ≥35% reduction from baseline in spleen volume as measured by magnetic resonance imaging (MRI) or computerized tomography (CT), and assessed by blinded central radiology read at Week 24.
- Secondary Outcome Measures
Name Time Method Number of Participants With TSS50 Response at Week 24 24 weeks of treatment A key secondary endpoint of the study is Total Symptom Score (TSS) response, defined as a ≥50% decrease from baseline in TSS as measured by the Myelofibrosis Symptom Assessment Form v4.0, which equals the sum of the 7 individual item responses on the 0-10 scale, with a possible total daily score that may range from 0 to 70, at Week 24. A higher Total Symptom Score indicates a higher disease burden and thus a worse outcome.
Baseline TSS is calculated as the average of non-missing daily total symptom scores over the 7- day period prior to day of randomization. The TSS for a treatment week is the average of non-missing daily total symptom scores over that week. However, the weekly TSS will be considered missing if there are less than 4 daily total symptom scores available for that week.Total Symptom Score Absolute Change From Baseline to Week 24 24 weeks of treatment A key secondary endpoint of the study is the absolute change in Total Symptom Score (TSS) at Week 24 compared to baseline as measured by the Myelofibrosis Symptom Assessment Form v4.0, which equals the sum of the 7 individual item responses on the 0-10 scale, with a possible total daily score that may range from 0 to 70. A higher TSS indicates a higher disease burden and thus a worse outcome.
Baseline TSS is calculated as the average of non-missing daily total symptom scores over the 7- day period prior to day of randomization. The TSS for a treatment week is the average of non-missing daily total symptom scores over that week. However, the weekly TSS will be considered missing if there are less than 4 daily total symptom scores available for that week.
Trial Locations
- Locations (156)
Decatur Memorial Hospital Cancer Care Center of Decatur/Cancer Care Specialists of IL
🇺🇸Decatur, Illinois, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Sunway Medical Centre
🇲🇾Petaling Jaya, Selangor, Malaysia
Maastricht University Medical Center
🇳🇱Maastricht, Netherlands
Hospital Virgen Macarena
🇪🇸Sevilla, Spain
Centre Hospitalier
🇫🇷Le Mans, France
University Hospital Salzburg
🇦🇹Salzburg, Austria
ZNA
🇧🇪Antwerpen, Belgium
Cliniques universitaires Saint-Luc
🇧🇪Brussel, Belgium
Domaine Universitaire du Sart Tilman
🇧🇪Liège, Belgium
Peninsula Private Hospital Clinical Trials Unit
🇦🇺Frankston, Victoria, Australia
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
LKH - Universitätsklinikum Graz; Abteilung für Hämatologie
🇦🇹Graz, Austria
Kepler University Hospital
🇦🇹Linz, Austria
Icon Cancer Centre
🇦🇺Brisbane, Queensland, Australia
Centre Hospitalier Lyon Sud Secteur 1G
🇫🇷Pierre-Bénite, France
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Gard Cancer Institute
🇫🇷Nîmes, France
Ironwood Physicians P.C. dba Ironwood Cancer and Research Centers
🇺🇸Chandler, Arizona, United States
UZ Leuven
🇧🇪Leuven, Belgium
: Pecs University, 1st Department of Medicine
🇭🇺Pécs, Pecs, Hungary
University Hospital of Toledo
🇪🇸Toledo, Spain
Morales Meseguer General University Hospital
🇪🇸Murcia, Spain
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Hospital Universitario de Gran Canaria Dr. Negrin
🇪🇸Las Palmas de Gran Canaria, Spain
The Catholic University of Korea
🇰🇷Seoul, Korea, Republic of
Center for Blood Disorders and Cellular Therapy, Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Krankenhaus der Elisabethinen Linz
🇦🇹Linz, Austria
Hôpital de Jolimont
🇧🇪La Louvière, Belgium
Hôpital Bretonneau
🇫🇷Tours, France
Institut de Cancérologie Lucien Neuwirth
🇫🇷Saint-Priest-en-Jarez, France
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Wojewódzki Szpital Specjalistyczny w Bialej Podlaskiej
🇵🇱Biała Podlaska, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Poland
:Hospital Ampang
🇲🇾Ampang, Selangor, Malaysia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Hospital Pulau Pinang
🇲🇾George Town, Penang, Malaysia
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
ICO Badalona - Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Spain
The Catholic University of South Korea Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Amsterdam UMC
🇳🇱Amsterdam, Netherlands
AOU S.Luigi Gonzaga
🇮🇹Orbassano, Italy
Hospital Queen Elizabeth
🇲🇾Kota Kinabalu, Malaysia
Chang Gung Memorial Hospital Chiayi
🇨🇳Chiayi City, Taiwan
Ankara University Faculty of Medicine Cebeci Research and Application Hospital
🇹🇷Ankara, Turkey
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Nasz Lekarz Przychodnie Medyczne
🇵🇱Toruń, Poland
King Chulalongkorn Memorial Hospital
🇹🇭Bangkok, Pathumwan, Thailand
Centrum Medyczne Pratia
🇵🇱Skorzewo, Poland
Dr. Abdurrahman Yurtaslan Oncology Health Application and Research Center
🇹🇷Ankara, Turkey
University Hospital Maggiore della Carità
🇮🇹Novara, Italy
Gaziantep University Sahinbey Research and Application Center Hospital
🇹🇷Gaziantep, Turkey
Pilgrim Hospital
🇬🇧Boston, United Kingdom
Inje University Haeundae Paik Hospital
🇰🇷Busan, Korea, Republic of
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
China Medical University Hospital
🇨🇳Chiayi City, Taiwan
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Antalya Medstar Hospital
🇹🇷Antalya, Turkey
Erciyes University Faculty of Medicine Hospital
🇹🇷Kayseri, Turkey
Quirónsalud Madrid University Hospital
🇪🇸Madrid, Spain
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Jeonbuk National University Hospital
🇰🇷Jeonju, Korea, Republic of
Hospital Sultanah Bahiyah
🇲🇾Alor Setar, Kedah, Malaysia
Vall d'Hebron Institute of Oncology
🇪🇸Barcelona, Spain
Chulabhorn Hospital
🇹🇭Bangkok, Lak Si, Thailand
Izmir Ege University Faculty of Medicine Hospital
🇹🇷İzmir, Turkey
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Edirne Trakya University Faculty of Medicine Hospital
🇹🇷Edirne, Turkey
Kocaeli University Application
🇹🇷Kocaeli, Turkey
Franciscan Health/Indiana blood and Marrow Transplantation
🇺🇸Indianapolis, Indiana, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Texas Health Science Center - San Antonio
🇺🇸San Antonio, Texas, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Hospital Sultanah Aminah
🇲🇾Johor Bahru, Johor, Malaysia
Songklanagarind Hospital
🇹🇭Songkla, Hat Yai District, Thailand
Srinagarind hospital,Khon Kaen University
🇹🇭Khon Kaen, Mueang Khon Kaen District, Thailand
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
University Hospital of Wales
🇬🇧Cardiff, Wales, United Kingdom
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Rajavithi Hospital
🇹🇭Bangkok, Ratchathewi District, Thailand
Western General Hospital
🇬🇧Edinburgh, Scotland, United Kingdom
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Azienda Ospedaliera Universitaria Arcispedale Sant'Anna
🇮🇹Ferrara, Italy
Mersin University
🇹🇷Mersin, Turkey
Samsun 19 Mayıs University Health Application Research Hospital
🇹🇷Samsun, Turkey
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
London Health Sciences Center - Victoria Hospital
🇨🇦London, Ontario, Canada
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Hospital San Pedro de Alcantara
🇪🇸Caceres, Spain
University Hospital Hamburg-Eppendorf
🇩🇪Hamburg, Germany
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Weill Cornell Medical College- New York Presbyterian Hospital
🇺🇸New York, New York, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
One Clinical Research PTY LTD
🇦🇺Nedlands, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
USC Clinical Trials Centre Sunshine Coast Haematology and Oncology Clinic
🇦🇺Buderim, Australia
Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
Chru Brabois
🇫🇷Vandœuvre-lès-Nancy, France
University Hospital Olomouc
🇨🇿Olomouc, Czechia
Chu Pontchaillou - Service Hematologie
🇫🇷Rennes, France
Hôpital l'Archet 1
🇫🇷Nice, France
Universitätsklinikum Ulm
🇩🇪Ulm, Baden-Württemberg, Germany
Universitätsklinikum Halle (Saale), Krukenberg-Krebszentrum Halle (KKH)
🇩🇪Halle, Sachsen, Germany
Laiko General Hospital
🇬🇷Athens, Greece
Universitätsklinikum Jena, Klinik für Innere Medizin II
🇩🇪Jena, Thüringen, Germany
University General Hospital of Patras
🇬🇷Río, Greece
UGH of Ioannina
🇬🇷Ioánnina, Greece
Princess Margaret Hospital
🇭🇰Hong Kong, Kowloon, Hong Kong
Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Soroka Medical Center
🇮🇱Be'er Sheva, Israel
Rambam Health Corporation
🇮🇱Haifa, Israel
Szabolcs Szatmár Bereg Megyei Kórházak és Egyetemi Oktatókórház; Jósa András Oktatókórház, Hematológia
🇭🇺Nyíregyháza, Hungary
Shamir Medical Center
🇮🇱Be'er Ya'aqov, Israel
Wolfson Medical Center
🇮🇱H̱olon, Israel
Shaarei Zedek
🇮🇱Nahariya, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Rabin Medical Center - Beilinson Campus,
🇮🇱Petah Tikva, Israel
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
🇮🇹Bergamo, Italy
A.O.U. Policlinico S. Orsola-Malpighi
🇮🇹Bologna, Italy
Regional Hospital Spedali Civili di Brescia
🇮🇹Brescia, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Florence, Italy
Azienda Ospedaliera San Gerardo di Monza
🇮🇹Monza, Italy
IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori"
🇮🇹Meldola, Italy
University Hospital 'Paolo Giaccone' Polyclinic
🇮🇹Palermo, Italy
Hospital Ordine Mauriziano of Turin
🇮🇹Turin, Italy
University Hospital of Padova
🇮🇹Padova, Italy
Ospedale Sant'Eugenio
🇮🇹Rome, Italy
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Gyeongsang National University Hospital
🇰🇷Jinju-si, Gyeongsangnam-do, Korea, Republic of
Ospedale di Circolo e Fondazione Macchi - ASST Sette Laghi
🇮🇹Varese, Italy
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
The Catholic University Of Korea St. Vincent Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
The Clatterbridge Cancer Centre
🇬🇧Liverpool, United Kingdom
Hospital Universitario de Salamanc
🇪🇸Salamanca, Spain
University College London Hospitals
🇬🇧London, United Kingdom
Daegu Catholic University Medical Center
🇰🇷Daegu, Korea, Republic of
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Norton Cancer Institute, St. Matthews Campus
🇺🇸Louisville, Kentucky, United States
Amiens South Hospital univerisy - Hopital Sud
🇫🇷Amiens, France
Hämatologisch-Onkologische Praxis Augsburg
🇩🇪Augsburg, Bayern, Germany
Hadassah University Hospital-Ein Kerem
🇮🇱Jerusalem, Israel
Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Oxford University Hospitals NHS Foundation Trust, Department of Haematology, Cancer and Haematology Centre, Churchill Hospital
🇬🇧Oxford, United Kingdom
Guy's & St Thomas NHS Foundation Trust
🇬🇧London, United Kingdom
Imperial College Healthcare NHS Trust, Hammersmith Hospital
🇬🇧London, United Kingdom
Prince of Wales Hospital
🇭🇰Hong Kong, New Territories, Hong Kong