Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)

Myelofibrosis Clinical Trial

— MANIFEST-2  

Official title:

A Phase 3, Randomized, Double-blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAKi Treatment Naive MF Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04603495
• Other study ID #: CPI 0610-04
• Secondary ID: 2020-001989-10
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 9, 2021
• Est. completion date: December 2027

Study information

• Verified date: April 2024
• Source: Constellation Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 430
• Est. completion date: December 2027
• Est. primary completion date: August 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Myelofibrosis
• Polycythemia
• Polycythemia Vera
• Post-essential Thrombocythemia Myelofibrosis
• Post-polycythemia Vera Myelofibrosis
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• Pelabresib
Double-blind treatment (pelabresib or matching placebo) will be administered daily for 14 consecutive days followed by a 7-day break, which is considered 1 cycle of treatment (1 cycle = 21 days). Pelabresib is a small molecule inhibitor of BET proteins with a novel mechanism of action and potential for disease-modifying effects in MF.
• Ruxolitinib
Ruxolitinib is a JAK inhibitor and a current, approved treatment option for MF.
• Placebo
Placebo tablets are designed to match pelabresib tablets. Each placebo tablet contains no active pharmaceutical ingredient and is visibly identical to experimental drug in size, shape, and packaging. Placebo dosing follows the same dosing conventions as pelabresib.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Icon Cancer Centre	Brisbane	Queensland
Australia	USC Clinical Trials Centre Sunshine Coast Haematology and Oncology Clinic	Buderim
Australia	Monash Health	Clayton	Victoria
Australia	Peninsula Private Hospital Clinical Trials Unit	Frankston	Victoria
Australia	One Clinical Research PTY LTD	Nedlands
Austria	LKH - Universitätsklinikum Graz; Abteilung für Hämatologie	Graz
Austria	Kepler University Hospital	Linz
Austria	Krankenhaus der Elisabethinen Linz	Linz
Austria	University Hospital Salzburg	Salzburg
Belgium	ZNA	Antwerpen
Belgium	Cliniques universitaires Saint-Luc	Brussel
Belgium	Hôpital de Jolimont	La Louvière
Belgium	UZ Leuven	Leuven
Belgium	Domaine Universitaire du Sart Tilman	Liège
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	London Health Sciences Center - Victoria Hospital	London	Ontario
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	University Hospital Olomouc	Olomouc
France	Amiens South Hospital univerisy - Hopital Sud	Amiens
France	Centre Hospitalier	Le Mans
France	Hôpital l'Archet 1	Nice
France	Gard Cancer Institute	Nîmes
France	Centre Hospitalier Lyon Sud Secteur 1G	Pierre-Bénite
France	Chu Pontchaillou - Service Hematologie	Rennes
France	Institut de Cancérologie Lucien Neuwirth	Saint-Priest-en-Jarez
France	Hôpital Bretonneau	Tours
France	Chru Brabois	Vandœuvre-lès-Nancy
Germany	Hämatologisch-Onkologische Praxis Augsburg	Augsburg	Bayern
Germany	Universitätsklinikum Halle (Saale), Krukenberg-Krebszentrum Halle (KKH)	Halle	Sachsen
Germany	University Hospital Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum Jena, Klinik für Innere Medizin II	Jena	Thüringen
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg
Greece	Laiko General Hospital	Athens
Greece	UGH of Ioannina	Ioánnina
Greece	University General Hospital of Patras	Río
Hong Kong	Prince of Wales Hospital	Hong Kong	New Territories
Hong Kong	Princess Margaret Hospital	Hong Kong	Kowloon
Hungary	Szabolcs Szatmár Bereg Megyei Kórházak és Egyetemi Oktatókórház; Jósa András Oktatókórház, Hematológia	Nyíregyháza
Hungary	: Pecs University, 1st Department of Medicine	Pécs	Pecs
Israel	Soroka Medical Center	Be'er Sheva
Israel	Shamir Medical Center	Be'er Ya'aqov
Israel	Wolfson Medical Center	H_olon
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Rambam Health Corporation	Haifa
Israel	Hadassah University Hospital-Ein Kerem	Jerusalem
Israel	Shaarei Zedek	Nahariya
Israel	Rabin Medical Center - Beilinson Campus,	Petah Tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
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 Arcispedale Sant'Anna	Ferrara
Italy	Azienda Ospedaliera Universitaria Careggi	Florence
Italy	IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori"	Meldola
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera San Gerardo di Monza	Monza
Italy	University Hospital Maggiore della Carità	Novara
Italy	AOU S.Luigi Gonzaga	Orbassano
Italy	University Hospital of Padova	Padova
Italy	University Hospital 'Paolo Giaccone' Polyclinic	Palermo
Italy	Ospedale Sant'Eugenio	Rome
Italy	Hospital Ordine Mauriziano of Turin	Turin
Italy	Ospedale di Circolo e Fondazione Macchi - ASST Sette Laghi	Varese
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Daegu Catholic University Medical Center	Daegu
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	Jeonbuk National University Hospital	Jeonju
Korea, Republic of	Gyeongsang National University Hospital	Jinju-si	Gyeongsangnam-do
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea	Seoul
Korea, Republic of	The Catholic University of South Korea Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan
Malaysia	Hospital Sultanah Bahiyah	Alor Setar	Kedah
Malaysia	:Hospital Ampang	Ampang	Selangor
Malaysia	Hospital Pulau Pinang	George Town	Penang
Malaysia	Hospital Sultanah Aminah	Johor Bahru	Johor
Malaysia	Hospital Queen Elizabeth	Kota Kinabalu
Malaysia	Sunway Medical Centre	Petaling Jaya	Selangor
Netherlands	Amsterdam UMC	Amsterdam
Netherlands	Maastricht University Medical Center	Maastricht
Poland	Wojewódzki Szpital Specjalistyczny w Bialej Podlaskiej	Biala Podlaska
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Pratia Onkologia Katowice	Katowice
Poland	Centrum Medyczne Pratia	Skorzewo
Poland	Nasz Lekarz Przychodnie Medyczne	Torun
Spain	ICO Badalona - Hospital Universitari Germans Trias i Pujol	Badalona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Vall d'Hebron Institute of Oncology	Barcelona
Spain	Hospital San Pedro de Alcantara	Caceres
Spain	Hospital Universitario de Gran Canaria Dr. Negrin	Las Palmas de Gran Canaria
Spain	Quirónsalud Madrid University Hospital	Madrid
Spain	Morales Meseguer General University Hospital	Murcia
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Hospital Universitario de Salamanc	Salamanca
Spain	Hospital Virgen Macarena	Sevilla
Spain	University Hospital of Toledo	Toledo
Spain	Hospital Clínico Universitario de Valencia	Valencia
Taiwan	Chang Gung Memorial Hospital Chiayi	Chiayi City
Taiwan	China Medical University Hospital	Chiayi City
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Chulabhorn Hospital	Bangkok	Lak Si
Thailand	King Chulalongkorn Memorial Hospital	Bangkok	Pathumwan
Thailand	Rajavithi Hospital	Bangkok	Ratchathewi District
Thailand	Srinagarind hospital,Khon Kaen University	Khon Kaen	Mueang Khon Kaen District
Thailand	Songklanagarind Hospital	Songkla	Hat Yai District
Turkey	Ankara University Faculty of Medicine Cebeci Research and Application Hospital	Ankara
Turkey	Dr. Abdurrahman Yurtaslan Oncology Health Application and Research Center	Ankara
Turkey	Antalya Medstar Hospital	Antalya
Turkey	Edirne Trakya University Faculty of Medicine Hospital	Edirne
Turkey	Gaziantep University Sahinbey Research and Application Center Hospital	Gaziantep
Turkey	Izmir Ege University Faculty of Medicine Hospital	Izmir
Turkey	Erciyes University Faculty of Medicine Hospital	Kayseri
Turkey	Kocaeli University Application	Kocaeli
Turkey	Mersin University	Mersin
Turkey	Samsun 19 Mayis University Health Application Research Hospital	Samsun
United Kingdom	Pilgrim Hospital	Boston
United Kingdom	Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Western General Hospital	Edinburgh	Scotland
United Kingdom	The Clatterbridge Cancer Centre	Liverpool
United Kingdom	Guy's & St Thomas NHS Foundation Trust	London
United Kingdom	Imperial College Healthcare NHS Trust, Hammersmith Hospital	London
United Kingdom	University College London Hospitals	London
United Kingdom	Oxford University Hospitals NHS Foundation Trust, Department of Haematology, Cancer and Haematology Centre, Churchill Hospital	Oxford
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Ironwood Physicians P.C. dba Ironwood Cancer and Research Centers	Chandler	Arizona
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Decatur Memorial Hospital Cancer Care Center of Decatur/Cancer Care Specialists of IL	Decatur	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	Franciscan Health/Indiana blood and Marrow Transplantation	Indianapolis	Indiana
United States	Mayo Clinic	Jacksonville	Florida
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	UCLA Medical Center	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Norton Cancer Institute, St. Matthews Campus	Louisville	Kentucky
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai	New York	New York
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	University of Texas Health Science Center - San Antonio	San Antonio	Texas
United States	Center for Blood Disorders and Cellular Therapy, Swedish Cancer Institute	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Constellation Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Netherlands,  Poland,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Splenic response at Week 24	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), at Week 24.	24 weeks of treatment
Secondary	Total Symptom Score absolute change from baseline to Week 24	A key secondary endpoint of the study is the absolute change in Total Symptom Score at Week 24 compared to baseline as measured by the Myelofibrosis Symptom Assessment Form v4.0. A higher Total Symptom Score indicates a higher disease burden and thus a worse outcome.	24 weeks of treatment
Secondary	Total Symptom Score response at Week 24	A key secondary endpoint of the study is Total Symptom Score response, defined as a =50% decrease from baseline in Total Symptom Score as measured by the Myelofibrosis Symptom Assessment Form v4.0, at Week 24. A higher Total Symptom Score indicates a higher disease burden and thus a worse outcome.	24 weeks of treatment