Clinical trial NCT04603495: Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Myelofibrosis
Primary Myelofibrosis
Post-polycythemia Vera Myelofibrosis
Post-essential Thrombocythemia Myelofibrosis
Keywords: Pelabresib
Ruxolitinib
Lead sponsor: Constellation Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-10-26
Enrollment: 430
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Splenic Response by Central Reads at Week 24
timeFrame: 24 weeks of treatment
Secondary outcomes:
measure: Total Symptom Score Absolute Change From Baseline to Week 24
timeFrame: 24 weeks of treatment
measure: Number of Participants With TSS50 Response at Week 24
timeFrame: 24 weeks of treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Chandler
country: United States
facility: Ironwood Physicians P.C. dba Ironwood Cancer and Research Centers
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Center of Decatur/Cancer Care Specialists of IL
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan Health/Indiana blood and Marrow Transplantation
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute, St. Matthews Campus
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College- New York Presbyterian Hospital
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center - San Antonio
state: Texas
city: Seattle
country: United States
facility: Center for Blood Disorders and Cellular Therapy, Swedish Cancer Institute
state: Washington
city: Brisbane
country: Australia
facility: Icon Cancer Centre
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Frankston
country: Australia
facility: Peninsula Private Hospital Clinical Trials Unit
state: Victoria
city: Buderim
country: Australia
facility: USC Clinical Trials Centre Sunshine Coast Haematology and Oncology Clinic
city: Nedlands
country: Australia
facility: One Clinical Research PTY LTD
city: Graz
country: Austria
facility: LKH - Universitätsklinikum Graz; Abteilung für Hämatologie
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen Linz
city: Linz
country: Austria
facility: Kepler University Hospital
city: Salzburg
country: Austria
facility: University Hospital Salzburg
city: Antwerpen
country: Belgium
facility: ZNA
city: Brussel
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: La Louvière
country: Belgium
facility: Hôpital de Jolimont
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: Domaine Universitaire du Sart Tilman
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: London
country: Canada
facility: London Health Sciences Center - Victoria Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Amiens
country: France
facility: Amiens South Hospital univerisy - Hopital Sud
city: Le Mans
country: France
facility: Centre Hospitalier
city: Nice
country: France
facility: Hôpital l'Archet 1
city: Nîmes
country: France
facility: Gard Cancer Institute
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud Secteur 1G
city: Rennes
country: France
facility: Chu Pontchaillou - Service Hematologie
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Tours
country: France
facility: Hôpital Bretonneau
city: Vandœuvre-lès-Nancy
country: France
facility: Chru Brabois
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: Augsburg
country: Germany
facility: Hämatologisch-Onkologische Praxis Augsburg
state: Bayern
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale), Krukenberg-Krebszentrum Halle (KKH)
state: Sachsen
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Klinik für Innere Medizin II
state: Thüringen
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf
city: Athens
country: Greece
facility: Laiko General Hospital
city: Ioánnina
country: Greece
facility: UGH of Ioannina
city: Río
country: Greece
facility: University General Hospital of Patras
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital
state: Kowloon
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
state: New Territories
city: Pécs
country: Hungary
facility: : Pecs University, 1st Department of Medicine
state: Pecs
city: Nyíregyháza
country: Hungary
facility: Szabolcs Szatmár Bereg Megyei Kórházak és Egyetemi Oktatókórház; Jósa András Oktatókórház, Hematológia
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Be'er Ya'aqov
country: Israel
facility: Shamir Medical Center
city: Haifa
country: Israel
facility: Rambam Health Corporation
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: H̱olon
country: Israel
facility: Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital-Ein Kerem
city: Nahariya
country: Israel
facility: Shaarei Zedek
city: Petah Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Campus,
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
city: Bologna
country: Italy
facility: A.O.U. Policlinico S. Orsola-Malpighi
city: Brescia
country: Italy
facility: Regional Hospital Spedali Civili di Brescia
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Universitaria Arcispedale Sant'Anna
city: Florence
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Meldola
country: Italy
facility: IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori"
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
city: Novara
country: Italy
facility: University Hospital Maggiore della Carità
city: Orbassano
country: Italy
facility: AOU S.Luigi Gonzaga
city: Padova
country: Italy
facility: University Hospital of Padova
city: Palermo
country: Italy
facility: University Hospital 'Paolo Giaccone' Polyclinic
city: Rome
country: Italy
facility: Ospedale Sant'Eugenio
city: Turin
country: Italy
facility: Hospital Ordine Mauriziano of Turin
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi - ASST Sette Laghi
city: Jinju-si
country: Korea, Republic of
facility: Gyeongsang National University Hospital
state: Gyeongsangnam-do
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Daegu Catholic University Medical Center
city: Gyeonggi-do
country: Korea, Republic of
facility: The Catholic University Of Korea St. Vincent Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea
city: Seoul
country: Korea, Republic of
facility: The Catholic University of South Korea Seoul St. Mary's Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Johor Bahru
country: Malaysia
facility: Hospital Sultanah Aminah
state: Johor
city: Alor Setar
country: Malaysia
facility: Hospital Sultanah Bahiyah
state: Kedah
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
state: Penang
city: Ampang
country: Malaysia
facility: :Hospital Ampang
state: Selangor
city: Petaling Jaya
country: Malaysia
facility: Sunway Medical Centre
state: Selangor
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Biała Podlaska
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Bialej Podlaskiej
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Skorzewo
country: Poland
facility: Centrum Medyczne Pratia
city: Toruń
country: Poland
facility: Nasz Lekarz Przychodnie Medyczne
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: ICO Badalona - Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr. Negrin
city: Madrid
country: Spain
facility: Quirónsalud Madrid University Hospital
city: Murcia
country: Spain
facility: Morales Meseguer General University Hospital
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanc
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Toledo
country: Spain
facility: University Hospital of Toledo
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Chiayi City
country: Taiwan
facility: Chang Gung Memorial Hospital Chiayi
city: Chiayi City
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Songkla
country: Thailand
facility: Songklanagarind Hospital
state: Hat Yai District
city: Bangkok
country: Thailand
facility: Chulabhorn Hospital
state: Lak Si
city: Khon Kaen
country: Thailand
facility: Srinagarind hospital,Khon Kaen University
state: Mueang Khon Kaen District
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
state: Pathumwan
city: Bangkok
country: Thailand
facility: Rajavithi Hospital
state: Ratchathewi District
city: Ankara
country: Turkey
facility: Ankara University Faculty of Medicine Cebeci Research and Application Hospital
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Oncology Health Application and Research Center
city: Antalya
country: Turkey
facility: Antalya Medstar Hospital
city: Edirne
country: Turkey
facility: Edirne Trakya University Faculty of Medicine Hospital
city: Gaziantep
country: Turkey
facility: Gaziantep University Sahinbey Research and Application Center Hospital
city: İzmir
country: Turkey
facility: Izmir Ege University Faculty of Medicine Hospital
city: Kayseri
country: Turkey
facility: Erciyes University Faculty of Medicine Hospital
city: Kocaeli
country: Turkey
facility: Kocaeli University Application
city: Mersin
country: Turkey
facility: Mersin University
city: Samsun
country: Turkey
facility: Samsun 19 Mayıs University Health Application Research Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: Boston
country: United Kingdom
facility: Pilgrim Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre
city: London
country: United Kingdom
facility: Guy's & St Thomas NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust, Hammersmith Hospital
city: London
country: United Kingdom
facility: University College London Hospitals
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust, Department of Haematology, Cancer and Haematology Centre, Churchill Hospital
Study officials:
References:
citation: Mascarenhas J, Kremyanskaya M, Patriarca A, Harrison C, Bose P, Rampal RK, Palandri F, Devos T, Passamonti F, Hobbs G, Talpaz M, Vannucchi A, Kiladjian JJ, Verstovsek S, Hoffman R, Salama ME, Chen D, Taverna P, Chang A, Colak G, Klein S, Gupta V. MPN-375 BET Inhibitor Pelabresib (CPI-0610) Combined With Ruxolitinib in Patients With Myelofibrosis - JAK Inhibitor-Naie or With Suboptimal Response to Ruxolitinib - Preliminary Data From the MANIFEST Study. Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S335-S336. doi: 10.1016/S2152-2650(22)01456-2.
citation: Harrison CN, Gupta VK, Gerds AT, Rampal R, Verstovsek S, Talpaz M, Kiladjian JJ, Mesa R, Kuykendall AT, Vannucchi AM, Palandri F, Grosicki S, Devos T, Jourdan E, Wondergem MJ, Al-Ali HK, Buxhofer-Ausch V, Alvarez-Larran A, Patriarca A, Kremyanskaya M, Mead AJ, Akhani S, Sheikine Y, Colak G, Mascarenhas J. Phase III MANIFEST-2: pelabresib + ruxolitinib vs placebo + ruxolitinib in JAK inhibitor treatment-naive myelofibrosis. Future Oncol. 2022 Sep;18(27):2987-2997. doi: 10.2217/fon-2022-0484. Epub 2022 Aug 11.