An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomitant JAK2 Inhibitor Therapy and Who Require Red Blood Cell Transfusions
- Conditions
- Myeloproliferative DisordersMyelofibrosisPrimary MyelofibrosisPost-Polycythemia Vera MyelofibrosisAnemia
- Interventions
- Other: Placebo
- Registration Number
- NCT04717414
- Lead Sponsor
- Celgene
- Brief Summary
The purpose of this Phase 3 study is to evaluate the efficacy and safety of Luspatercept compared with placebo in subjects with myeloproliferative neoplasm (MPN)-associated Myelofibrosis (MF) and anemia on concomitant Janus kinase 2 (JAK2) inhibitor therapy and who require red blood cell count (RBC) transfusions.
The study is divided into Screening Period, a Treatment Phase (consisting of a Blinded Core Treatment Period, a Day 169 Response Assessment, a Blinded Extension Treatment Period, and an Open-label Extension Treatment Period), and a Posttreatment Follow-up Period.
Following the Day 169 Response Assessment, subjects who did not show clinical benefit will have the option to unblind. Subjects who were on placebo during the Blinded Core Treatment Period will have the opportunity to crossover into the Open-Label Extension Treatment Period and receive Luspatercept.
- Detailed Description
Permitted Concomitant Medications and Procedures
* Subjects are receiving a JAK2 inhibitor for the treatment of MPN-associated MF that is approved in the country where the study is being conducted. JAK2 inhibitors are to be used according to their respective label and as prescribed as part of the subject's standard-of-care therapy as prescribed by their physician prior to study entry.
* Best supportive care (BSC) includes, but is not limited to, treatment with transfusions (eg, RBC, platelet, whole blood), ICTs, antibiotic, antiviral and/or antifungal therapy, and nutritional support as needed.
* Granulocyte colony-stimulating factors (ie, G-CSF, granulocyte macrophage colony-stimulating factor \[GM-CSF\]) are allowed only in cases of neutropenic fever or as clinically indicated per product label.
* Prophylactic antithrombotic therapy is permitted.
* Thrombopoietin and platelet transfusions are permitted.
* Treatment with systemic corticosteroids is permitted for nonhematological conditions providing the subject is receiving a constant dose equivalent to ≤ 10 mg prednisone during the study.
* Administration of attenuated vaccines (eg, influenza vaccine) is allowed if clinically indicated per Investigator discretion.
* Iron chelation therapy (ICT) is to be used according to the product label. If the label permits, the ICT dose should be stable during at least the first 24 weeks of IP. Initiation of ICT while within the first 24 weeks of IP should be clinically indicated to treat an AE.
Prohibited Concomitant Medications
The following concomitant medications are specifically excluded during the course of study treatment:
* Cytotoxic, chemotherapeutic, targeted, or investigational agents/therapies (excluding JAK2 inhibitor therapy)
* Azacitidine, decitabine, or other hypomethylating agents
* Lenalidomide, thalidomide, and pomalidomide
* Erythropoietin stimulating agents (ESAs) and other RBC hematopoietic growth factors (eg, IL-3)
* Hydroxyurea or other alkylating agents
* Androgens (unless given to treat hypogonadism)
* Oral retinoids (topical retinoids are permitted)
* Arsenic trioxide
* Interferon
* Anagrelide
* Systemic corticosteroids at a dose equivalent to \> 10 mg prednisone
* Investigational products for the treatment of MPN-associated MF
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 309
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental Arm: Luspatercept (ACE-536) ACE-536 Luspatercept will be given to participants via subcutaneous injection (administered on Day 1 of each 21-day treatment cycle) Control Arm: Placebo Placebo Placebo starting dose with volume equivalent to experimental arm subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle)
- Primary Outcome Measures
Name Time Method Red blood cell-transfusion independence (RBC-TI) ≥ 12 weeks (RBC-TI 12) Up to 24 weeks Proportion of subjects who become RBC-transfusion free over any consecutive 12-week period starting within the first 24 weeks.
- Secondary Outcome Measures
Name Time Method Red blood cell-transfusion independence ≥ 16 weeks (RBC-TI 16) Up to 24 weeks Proportion of subjects who become RBC-transfusion free over any consecutive 16-week period
Duration of Red blood cell-transfusion independence (RBC-TI 12) Up to end of treatment, approximately 3 years Maximum duration of RBC-TI response
Reduction of transfusion burden by ≥ 50% and by ≥ 4 units/12 weeks from baseline over any consecutive 12-week period Up to 24 weeks Proportion of subjects who reduce their transfusion burden by ≥ 50% and by ≥ 4 units/12 weeks from baseline over any consecutive 12-week period
Duration of reduction in transfusion burden Up to end of treatment, approximately 3 years Maximum duration of when RBC-transfusion dependent subjects who reduce their transfusion burden by ≥ 50% and by ≥ 4 units/12 weeks from baseline over any consecutive 12 week period
Red blood cell-transfusion independence ≥ 12 weeks in the treatment period (RBC-TI 12/TP) Up to end of treatment, approximately 3 years Proportion of subjects who become RBC-transfusion free over any consecutive 12-week period
Red blood cell-transfusion independence ≥ 16 weeks in the treatment period (RBC-TI 16/TP) Up to end of treatment, approximately 3 years Proportion of subjects who become RBC-transfusion free over any consecutive 16-week period
Change in RBC transfusion burden Up to 24 weeks Mean change in transfusion burden (RBC units) from baseline
Cumulative duration of RBC-transfusion independence Up to end of treatment, approximately 3 years Cumulative response duration for subjects achieving multiple episodes of RBC-TI 12
Mean Hgb increase ≥ 1 g/dL from baseline over any consecutive 12-week period in absence of RBC transfusions Up to end of treatment, approximately 3 years Proportion of subjects achieving a mean Hgb increase ≥ 1 g/dL from baseline over any consecutive 12-week period in absence of RBC transfusions
Change in serum ferritin from baseline Up to end of treatment, approximately 3 years Change in serum ferritin
Incidence of Adverse Events (AEs) From screening up to 42 days post last dose Number of participants with adverse events
Transformation to blast phase: Number of subjects who transform into AML Up to approximately 5 years AML = acute myeloid leukemia
Frequency of Antidrug antibodies (ADA) From randomization and up to including 48 weeks post first dose Will be collected for assessment of anti-drug antibodies (ADA) against Luspatercept in serum in all subjects
Pharmacokinetics - Area Under the Concentration-Time Curve (AUC) From randomization and up to including 48 weeks post first dose Measures of luspatercept exposure area under the curve
Pharmacokinetics - Maximum plasma concentration of drug (Cmax) From randomization and up to including 48 weeks post first dose Maximum plasma concentration of drug
Trial Locations
- Locations (208)
University Of California Los Angeles
🇺🇸Los Angeles, California, United States
BRCR Medical Center Inc.
🇺🇸Plantation, Florida, United States
Local Institution - 112
🇺🇸Chicago, Illinois, United States
University Of Kentucky Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Local Institution - 108
🇺🇸Saint Louis, Missouri, United States
John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
University of Pittsburg Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Allegheny Health Network
🇺🇸Pittsburgh, Pennsylvania, United States
Hospital Italiano de La Plata
🇦🇷La Plata, Buenos Aires, Argentina
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Royal Hobart Hospital
🇦🇺Hobart, Australia
Gosford Hospital
🇦🇺Gosford, Australia
Krankenhaus der Elisabethinen Linz, I Interne Abteilung
🇦🇹Linz, Austria
Local Institution - 274
🇦🇹Vienna, Austria
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
AZ Sint-Jan AV Brugge
🇧🇪Brugge, Belgium
Local Institution - 313
🇧🇪Hasselt, Belgium
Uz Leuven
🇧🇪Leuven, Belgium
Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman
🇧🇪Liège, Belgium
AZ Delta vzw
🇧🇪Roeselare, Belgium
Centre Hospitalier Peltzer - La Tourelle
🇧🇪Verviers, Belgium
University Of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
University Hospital - London Health Sciences Centre
🇨🇦London, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Sir Mortimer B. Davis - Jewish Genl
🇨🇦Montreal, Quebec, Canada
IC La Serena Research
🇨🇱La Serena, Coquimbo, Chile
Hospital Pablo Tobon Uribe
🇨🇴Medellin, Antioquia, Colombia
Instituto Nacional De Cancerologia
🇨🇴Bogota, Distrito Capital De Bogotai, Colombia
Vseobecna Fakultni Nemocnice V Praze
🇨🇿Prague 2, Czechia
Fundacion Oftalmologica De Santander - Foscal
🇨🇴Floridablanca, Soto, Colombia
CHRU Hopital du bocage
🇫🇷Angers, France
Local Institution - 324
🇫🇷Creteil, France
Chu De Grenoble
🇫🇷Grenoble, France
Chu Estaing
🇫🇷Clermont Ferrand, France
CHRU de Lille-Hopital Claude Huriez
🇫🇷Lille, France
Centre Leon Berard
🇫🇷Lyon, France
CHU de Nice Archet I
🇫🇷Nice, France
Hopital Saint Louis
🇫🇷Paris Cedex 10, France
Centre Hospitalier Universitaire de Nimes (CHU) - Hopital Universitaire Caremeau
🇫🇷Nimes Cedex 9, France
Groupe Hospitalier Sud Hopital Haut Leveque USN
🇫🇷Pessac, France
CHU La Miletrie
🇫🇷Poitiers Cedex, France
Local Institution - 330
🇫🇷Toulouse Cedex 9, France
ICANS Institut de cancerologie Strasbourg Europe
🇫🇷Strasbourg, France
Stauferklinikum Schwab. Gmund
🇩🇪Baden-Warttemberg, Germany
Unviversitatsklinikum Aachen
🇩🇪Aachen, Germany
Universitaetsklinikum Duesseldorf
🇩🇪Dusseldorf, Germany
Universitatsklinikum Halle Saale
🇩🇪Halle, Germany
Local Institution - 300
🇩🇪Hamburg, Germany
Universitatsklinikum Leipzig
🇩🇪Leipzig, Germany
Universitaetsklinikum Jena
🇩🇪Jena, Germany
Local Institution - 301
🇩🇪Mannheim, Germany
Attikon University General Hospital
🇬🇷Athens, Greece
Johannes Wiesling Klinikum Minden
🇩🇪Minden, Germany
Local Institution - 387
🇬🇷Patra, Achaia, Greece
University Hospital of Alexandroupolis
🇬🇷Alexandroupolis, Greece
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Petz Aladár Egyetemi Oktató Kórház
🇭🇺Gyor, Hungary
Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet
🇭🇺Budapest, Hungary
Mater Misercordiae Hospital
🇮🇪Dublin 7, Ireland
St James Hospital
🇮🇪Dublin, Ireland
Tel-Aviv Sourasky Medical Center
🇮🇱Tel-Aviv, Tel Aviv, Israel
Meir Medical Center
🇮🇱Kfar-Saba, Israel
Hadassah Medical Organization
🇮🇱Jerusalem, Israel
Rambam Medical Center
🇮🇱Haifa, Israel
Shamir Medical Center - Assaf Harofeh
🇮🇱Zerifin, Israel
IRCCS - Istituto Romagnolo per lo Studio Dei Tumori "Dino Amadori" (IRST)
🇮🇹Meldola (fc), Fc, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I, G.M. Lancisi, G. Salesi
🇮🇹Ancona, Italy
Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
🇮🇹Bologna, Italy
Asst Spedali Civili Di Brescia
🇮🇹Brescia, Italy
Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele - Ospedale Gaspare Rodolico
🇮🇹Catania, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Azienda Ospedaliera Di Padova
🇮🇹Padova, Italy
Azienda Ospedaliera Universitaria Federico Ii
🇮🇹Napoli Campania, Italy
A.O.U. Maggiore della Carit
🇮🇹Novara, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
🇮🇹Reggio Di Calabria, Italy
Azienda Ospedaliera Sant Andrea
🇮🇹Roma, Italy
Local Institution - 245
🇮🇹Terni, Italy
A.O.U. Citta Della Salute E Della Scienza , Presidio Molinette,S.C. Ematologia Universitaria
🇮🇹Torino, Italy
Centro Ricerche Cliniche di Verona S.r.l.
🇮🇹Verona, Italy
Universita degli Studi dell'Insubria - Ospedale di Circolo e Fondazione Macchi - Varese
🇮🇹Varese, Italy
The Japanese Red Cross Nagasaki Genbaku Hospital
🇯🇵Nagasaki-shi, Nagasaki, Japan
Kindai University Hospital- Osakasayama Campus
🇯🇵Osakasayama, Osaka, Japan
Juntendo University Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
Aomori Prefectural Central Hospital
🇯🇵Aomori, Japan
Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
🇯🇵Bunkyo-ku, Japan
University of Yamanashi Hospital
🇯🇵Chuo, Japan
Tokai University Hospital
🇯🇵Isehara City, Kanagawa, Japan
Local Institution - 717
🇯🇵Kamakura, Japan
Kameda General Hospital
🇯🇵Kamogawa, Japan
Local Institution - 706
🇯🇵Maebashi, Japan
University of Miyazaki Hospital
🇯🇵Miyazaki, Japan
Local Institution - 708
🇯🇵Sapporo, Japan
Ogaki Municipal Hospital
🇯🇵Ogaki, Japan
Osaka Metropolitan university Hospital
🇯🇵Osaka, Japan
NTT Medical Center Tokyo
🇯🇵Shinagawa-ku, Tokyo, Japan
Tokyo Women's Medical University Hospital
🇯🇵Shinjuku City, Japan
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
The Catholic University of Korea Seoul - Saint Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hammoud Hospital University Medical Center
🇱🇧Saida, South, Lebanon
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
American Univ of Beirut Med Center
🇱🇧Badaro Beirut, Lebanon
LAU Medical Center Rizk Hospital
🇱🇧Beirut, Lebanon
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
ALVAMED
🇵🇱Poznan, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
Specjalistyczny Szpital im. dra Alfreda Sokolowskiego
🇵🇱Walbrzych, Poland
Spitalul Clinic Municipal Filantropia Craiova
🇷🇴Craiova, Dolj, Romania
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
🇵🇱Wroclaw, Poland
Onco Card SRL
🇷🇴Brasov, Romania
Fundeni Clinical Institute
🇷🇴Bucharest, Romania
Local Institution - 500
🇷🇺Moscow, Russian Federation
Local Institution - 503
🇷🇺St. Petersburg, Russian Federation
Local Institution - 502
🇷🇺St Petersburg, Russian Federation
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari Germans Trias i Pujol ICO Badalona
🇪🇸Barcelona, Spain
Hospital Virgenes de las Nieves
🇪🇸Granada, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Local Institution - 202
🇪🇸Palma de Mallorca, Spain
Hospital Universitario De Gran Canaria Dr. Negrin
🇪🇸Las Palmas de Gran Canaria, Spain
Universitario de Salamanca - Hospital Clinico
🇪🇸Salamanca, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Seville, Spain
Complejo Hospitalario Universitario De Santiago
🇪🇸Santiago de Compostela, Spain
Hospital Clinico Universitario De Valencia
🇪🇸Valencia, Spain
Churchhill Hospital
🇬🇧Oxford, United Kingdom
United Lincolnshire Hospitals NHS Trust
🇬🇧Boston, United Kingdom
The First Affiliated Hospital of Nanyang Medical College
🇨🇳Nanyang, Henan, China
Xiangya Hospital Central-South University
🇨🇳Changsha, Hunan, China
Affiliated Hospital of Nantong University
🇨🇳Nantong, Jiangsu, China
The First Affiliated Hospital of NanChang University
🇨🇳Nanchang, Jiangxi, China
Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University
🇨🇳Nanjing, Jiangsu, China
Nanfang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Nanchang University - The Second Affiliated Hospital
🇨🇳Nanchang, Jiangxi, China
The Affiliated Hospital Of Qingdao University
🇨🇳Qingdao, Shandong, China
Second Hospital of Shanxi Medical University
🇨🇳Taiyuan, Shanxi, China
The Second Affiliated Hospital Of Kunming Medical University
🇨🇳Kunming, Yunnan, China
First Hospital of Jilin University
🇨🇳Changchun, China
Guangdong General Hospital
🇨🇳Guangzhou, China
The First Affiliated Hospital Of Harbin Medical University
🇨🇳Harbin, China
Ruijin Hospital Shanghai Jiaotong University
🇨🇳Shanghai, China
Shanghai 6th Hospital
🇨🇳Shanghai, China
The First Affiliated Hospital Of Soochow University
🇨🇳Suzhou, China
Chinese Academy of Medical Sciences & Peking Union Medical College
🇨🇳Tianjin, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, China
Beijing Peking Union Medical College Hospital
🇨🇳Beijing, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
Hopital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
Evangelismos General Hospital of Athens
🇬🇷Athens, Greece
Local Institution - 176
🇨🇦Sherbrooke, Quebec, Canada
Local Institution - 181
🇨🇦Calgary, Alberta, Canada
Enroll SpA - PPDS
🇨🇱Santiago, Chile
University General Hospital of Patras
🇬🇷Rio Patras, Greece
Prince of Wales Hospital the Chinese University of Hong Kong
🇭🇰Sha Tin, Hong Kong
Cork University Hospital
🇮🇪Cork, Ireland
Local Institution - 271
🇦🇹Vienna, Austria
Georgios Papanikolaou General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
St. Paul'S Hospital
🇨🇦Vancouver, British Columbia, Canada
Cliniques Universitaires UCL de Mont-Godine
🇧🇪Yvoir, Belgium
Local Institution - 386
🇬🇷Athens, Greece
Toyohashi Municipal Hospital
🇯🇵Toyohashi, Japan
Hospital Britanico de Buenos Aires
🇦🇷Ciudad Autónoma de BuenosAires, Buenos Aires, Argentina
Centro de Oncología de Precisión
🇨🇱Las Condes, Metropolitana De Santiago, Chile
Local Institution - 710
🇯🇵Shinjyuku-ku, Japan
Wojewódzki Szpital Specjalistyczny im. M. Kopernika w Lodzi
🇵🇱Lodz, Poland
Prof. Dr. I. Chiricuta Institute of Oncology
🇷🇴Cluj-Napoca, Romania
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Nottingham City Hospital
🇬🇧Nottingham, Nottinghamshire, United Kingdom
Local Institution - 272
🇦🇹Graz, Austria
Azienda Policlinico Universitario Umberto I
🇮🇹Roma, Italy
Ospedale S Eugenio
🇮🇹Roma, Italy
Heart of England NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Chonnam National University Hwasun Hospital
🇰🇷Hwasun-Gun, Korea, Republic of
Local Institution - 114
🇺🇸Ann Arbor, Michigan, United States
The University of Texas - MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Utah - Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Local Institution - 135
🇺🇸Orlando, Florida, United States
Hospital Universitario 12 De Octubre
🇪🇸Madrid, Spain
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Local Institution - 110
🇺🇸Los Angeles, California, United States
Local Institution - 124
🇺🇸Lexington, Kentucky, United States
Local Institution - 130
🇺🇸Knoxville, Tennessee, United States
Local Institution - 119
🇺🇸Salt Lake City, Utah, United States
Local Institution - 172
🇦🇷Ciudad Autónoma de BuenosAires, Buenos Aires, Argentina
Local Institution - 318
🇧🇪Brugge, Belgium
Local Institution - 312
🇧🇪Brussels, Belgium
Local Institution - 316
🇧🇪Roeselare, Belgium
Local Institution - 315
🇧🇪Verviers, Belgium
Local Institution - 179
🇨🇦Edmonton, Alberta, Canada
Local Institution - 183
🇨🇦Vancouver, British Columbia, Canada
Local Institution - 177
🇨🇦Montreal, Quebec, Canada
Local Institution - 192
🇨🇱Las Condes, Metropolitana De Santiago, Chile
Local Institution - 193
🇨🇱Santiago, Chile
Local Institution - 804
🇨🇳Nanjing, Jiangsu, China
Local Institution - 818
🇨🇳Nantong, Jiangsu, China
Local Institution - 820
🇨🇳Nanchang, Jiangxi, China
Local Institution - 821
🇨🇳Qingdao, Shandong, China
Local Institution - 816
🇨🇳Taiyuan, Shanxi, China
Local Institution - 802
🇨🇳Changchun, China
Local Institution - 319
🇧🇪Liège, Belgium
Local Institution - 180
🇨🇦Toronto, Ontario, Canada
Local Institution - 133
🇺🇸Plantation, Florida, United States