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

Anemia Clinical Trial

— INDEPENDENCE  

Official title:

A Phase 3, Double-blind, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomitant JAK Inhibitor Therapy and Who Require Red Blood Cell Transfusions

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04717414
• Other study ID #: ACE-536-MF-002
• Secondary ID: 2020-000607-36U1
• Status: Recruiting
• Phase: Phase 3
• Start date: February 25, 2021
• Est. completion date: August 23, 2025

Study information

• Verified date: June 2024
• Source: Celgene
• Contact: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 309
• Est. completion date: August 23, 2025
• Est. primary completion date: March 27, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Subjects must satisfy the following criteria to be randomized in the study:

Inclusion Criteria

• Subject is =18 years of age at the time of signing the ICF.

• Subject has a diagnosis of PMF according to the 2016 World Health Organization (WHO) criteria or diagnosis of post-ET or post-PV MF according to the IWG-MRT 2007 criteria, confirmed by the most recent local pathology report.

• Subject is requiring RBC transfusions as defined as:.

i) Average RBC-transfusion frequency: 4 to 12 RBC units/12 weeks immediately up to randomization. There must be no interval > 6 weeks (42 days) without = 1 RBC transfusion.

ii) RBC transfusions are scored in determining eligibility when given for treatment of:.

A. Symptomatic (ie, fatigue or shortness of breath) anemia with a pretransfusion Hgb = 9.5 g/dL or.

B. Asymptomatic anemia with a pretransfusion Hgb = 7 g/dL.

iii) RBC transfusions given for worsening of anemia due to bleeding or infections are not scored in determining eligibility.

• Subjects on continuous (eg, absent of dose interruptions lasting = 2 consecutive weeks) JAK2 inhibitor therapy as approved in the country of the study site for the treatment for MPN-associated MF as part of their standard-of-care therapy for at least 32 weeks, on stable daily dose for at least 16 weeks immediately up to the date of randomization and anticipated to be on a stable daily dose of that JAK2 inhibitor for at least 24 weeks after randomization.

• Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of = 2.

• A female of childbearing potential (FCBP) for this study is defined as a female who:

1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (eg, has had menses at any time in the preceding 24 consecutive months). Females of childbearing potential (FCBP)participating in the study must:.

i) Have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the study, and after end of IP. This applies even if the subject practices true abstinence* from heterosexual contact.

ii) Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception** without interruption, 28 days prior to starting IP, during the study therapy (including dose interruptions), and for 12 weeks (approximately 5 times the mean terminal half-life of IP based on multiple-dose PK data) after discontinuation of study therapy.

• Male subjects must: Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential** while participating in the study, during dose interruptions and for at least 12 weeks (approximately 5 times the mean terminal half-life of IP based on multiple-dose PK data) following IP discontinuation, even if he has undergone a successful vasectomy.

i) True abstinence is acceptable when it is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.].

ii) Agreement to use highly effective methods of contraception that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly throughout the course of the study. Such methods include: Combined (estrogen and progestogen containing) hormonal contraception: Oral, Intravaginal, Transdermal; Progestogen-only hormonal contraception associated with inhibition of ovulation: Oral, Injectable hormonal contraception, Implantable hormonal contraception; Placement of an intrauterine device (IUD); Placement of an intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomized partner; Sexual Abstinence.

• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.

• Subject is willing and able to adhere to the study visit schedule and other protocol requirements including the use of the electronic patient reported outcomes device.

Exclusion Criteria

• The presence of any of the following will exclude a subject from randomization:.

• Subject with anemia from cause other than MPN-associated MForJAK2 inhibitor therapy (eg, iron deficiency, vitamin B12 and/or folate deficiencies, autoimmune or hemolytic anemia, infection, or any type of known clinically significant bleeding or sequestration).

• Subject use of hydroxyurea, immunomodulatory compounds such as pomalidomide, thalidomide, ESAs, androgenic steroids or other drugs with potential effects on hematopoiesis = 8 weeks immediately up to the date of randomization.

i) Systemic corticosteroids are permitted for nonhematological conditions providing the subject is receiving a constant dose equivalent to = 10 mg prednisone for the 4 weeks immediately up to randomization.

ii) Iron chelation therapy (ICT) is permitted providing the subject is receiving a stable dose for the 8 weeks immediately up to randomization.

• Subject with any of the following laboratory abnormalities at screening:.

i) Neutrophils: < 1 x 10^9/L.

ii) White blood count (WBC): > 100 x 10^9/L.

iii) Platelets: the lowest allowable level as approved for the concomitant JAK2 inhibitor but not < 25 x 10^9/L or > 1000 x 10^9/L.

iv) Peripheral blood myeloblasts:> 5%.

v) Estimated glomerular filtration rate:< 30 mL/min/1.73 m2 (via the 4-variable modification of diet in renal disease [MDRD] formula) or nephrotic subjects (eg, urine albumin-to-creatinine ratio > 3500 mg/g).

vi) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT):> 3.0 x upper limit of normal (ULN).

vii) Direct bilirubin: = 2 x ULN.

A. Higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within the bone marrow (eg, ineffective erythropoiesis).

• Subject with uncontrolled hypertension, defined as repeated elevations of systolic blood pressure = 140 mmHg or diastolic blood pressure = 90 mmHg, that is not resolved at the time of randomization.

• Subject with prior history of malignancies, other than disease under study, unless the subject has been free of the disease for = 3 years. However, subject with the following history/concurrent conditions is allowed:.

i) Basal or squamous cell carcinoma of the skin.

ii) Carcinoma in situ of the cervix.

iii) Carcinoma in situ of the breast.

iv) Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system).

• Subject with prior hematopoietic cell transplant or subject anticipated to receive a hematopoietic cell transplant during the 24 weeks from the date of randomization. 7. Subject with stroke, myocardial infarction, deep venous thrombosis, pulmonary or arterial embolism within 6 months immediately up to the date of randomization.

• Subject with major surgery within 2 months up to the date of randomization. Subject must have completely recovered from any previous surgery immediately up to the date of randomization.

• Subject with a major bleeding event (defined as symptomatic bleeding in a critical area or organ and/or bleeding causing a decrease in Hgb of = 2 g/dL or leading to transfusion of = 2 units of packed red cells) in the last 6 months prior to the date of randomization.

• Subject with inadequately controlled heart disease and/or have a known left ventricular ejection fraction < 35%.

• Subject with uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment).

• Subject with known human immunodeficiency virus (HIV), evidence of active Hepatitis B (HepB) as demonstrated by the presence of Hepatitis B surface antigen (HBsAg) and/or positive for Hepatitis B virus DNA (HBVDNA-positive), and/or evidence of active Hepatitis C (HepC) as demonstrated by a positive Hepatitis C virus RNA (HCV-RNA) test of sufficient sensitivity.

• Subject with prior therapy of luspatercept or sotatercept.

• Subject with history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product.

• Pregnant or breastfeeding females.

• Subject participation in any other clinical protocol or investigational trial that involves use of experimental therapy (including investigational agents) and/or therapeutic devices within 30 days or for investigational agents within five half-lives, whichever comes later, immediately up to the date of randomization.

• Subject with any significant medical condition, laboratory abnormality, psychiatric illness, or is considered vulnerable by local regulations (eg, imprisoned or institutionalized) that would prevent the subject from participating in the study or places the subject at unacceptable risk if he/she were to participate in the study. 18.Subject with any condition or concomitant medication that confounds the ability to interpret data from the study.

• Other protocol-defined Inclusion/Exclusion criteria apply.

Related Conditions & MeSH terms

• Anemia
• Myelofibrosis
• Myeloproliferative Disorders
• Neoplasms
• Polycythemia
• Polycythemia Vera
• Post-Polycythemia Vera Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• ACE-536
Subcutaneous Injection

Other:
• Placebo
Subcutaneous Injection

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires
Argentina	Hospital Britanico de Buenos Aires	Ciudad Autónoma de BuenosAires	Buenos Aires
Argentina	Hospital Italiano de La Plata	La Plata	Buenos Aires
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Gosford Hospital	Gosford
Australia	Royal Hobart Hospital	Hobart
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Austria	Local Institution - 272	Graz
Austria	Krankenhaus der Elisabethinen Linz, I Interne Abteilung	Linz
Austria	Local Institution - 271	Vienna
Austria	Local Institution - 274	Vienna
Belgium	AZ Sint-Jan AV Brugge	Brugge
Belgium	Cliniques Universitaires Saint-Luc	Brussels
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	Cliniques Universitaires UCL de Mont-Godine	Yvoir
Canada	Local Institution - 181	Calgary	Alberta
Canada	University Of Alberta Hospital	Edmonton	Alberta
Canada	University Hospital - London Health Sciences Centre	London	Ontario
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Sir Mortimer B. Davis - Jewish Genl	Montreal	Quebec
Canada	Local Institution - 176	Sherbrooke	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	St. Paul'S Hospital	Vancouver	British Columbia
Chile	IC La Serena Research	La Serena	Coquimbo
Chile	Centro de Oncología de Precisión	Las Condes	Metropolitana De Santiago
Chile	Enroll SpA - PPDS	Santiago
China	Beijing Peking Union Medical College Hospital	Beijing
China	First Hospital of Jilin University	Changchun
China	Xiangya Hospital Central-South University	Changsha	Hunan
China	Guangdong General Hospital	Guangzhou
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital Of Harbin Medical University	Harbin
China	The Second Affiliated Hospital Of Kunming Medical University	Kunming	Yunnan
China	Nanchang University - The Second Affiliated Hospital	Nanchang	Jiangxi
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	Affiliated Hospital of Nantong University	Nantong	Jiangsu
China	The First Affiliated Hospital of Nanyang Medical College	Nanyang	Henan
China	The Affiliated Hospital Of Qingdao University	Qingdao	Shandong
China	Ruijin Hospital Shanghai Jiaotong University	Shanghai
China	Shanghai 6th Hospital	Shanghai
China	The First Affiliated Hospital Of Soochow University	Suzhou
China	Second Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Chinese Academy of Medical Sciences & Peking Union Medical College	Tianjin
China	Tianjin Medical University General Hospital	Tianjin
China	Henan Cancer Hospital	Zhengzhou
Colombia	Instituto Nacional De Cancerologia	Bogota	Distrito Capital De Bogotai
Colombia	Fundacion Oftalmologica De Santander - Foscal	Floridablanca	Soto
Colombia	Hospital Pablo Tobon Uribe	Medellin	Antioquia
Czechia	Vseobecna Fakultni Nemocnice V Praze	Prague 2
France	CHRU Hopital du bocage	Angers
France	Chu Estaing	Clermont Ferrand
France	Local Institution - 324	Creteil
France	Chu De Grenoble	Grenoble
France	CHRU de Lille-Hopital Claude Huriez	Lille
France	Centre Leon Berard	Lyon
France	CHU de Nice Archet I	Nice
France	Centre Hospitalier Universitaire de Nimes (CHU) - Hopital Universitaire Caremeau	Nimes Cedex 9
France	Hopital Saint Louis	Paris Cedex 10
France	Groupe Hospitalier Sud Hopital Haut Leveque USN	Pessac
France	CHU La Miletrie	Poitiers Cedex
France	ICANS Institut de cancerologie Strasbourg Europe	Strasbourg
France	Local Institution - 330	Toulouse Cedex 9
Germany	Unviversitatsklinikum Aachen	Aachen
Germany	Stauferklinikum Schwab. Gmund	Baden-Warttemberg
Germany	Universitaetsklinikum Duesseldorf	Dusseldorf
Germany	Universitatsklinikum Halle Saale	Halle
Germany	Local Institution - 300	Hamburg
Germany	Universitaetsklinikum Jena	Jena
Germany	Universitatsklinikum Leipzig	Leipzig
Germany	Local Institution - 301	Mannheim
Germany	Johannes Wiesling Klinikum Minden	Minden
Greece	University Hospital of Alexandroupolis	Alexandroupolis
Greece	Attikon University General Hospital	Athens
Greece	Evangelismos General Hospital of Athens	Athens
Greece	Local Institution - 386	Athens
Greece	Local Institution - 387	Patra	Achaia
Greece	University General Hospital of Patras	Rio Patras
Greece	Georgios Papanikolaou General Hospital of Thessaloniki	Thessaloniki
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital the Chinese University of Hong Kong	Sha Tin
Hungary	Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet	Budapest
Hungary	Petz Aladár Egyetemi Oktató Kórház	Gyor
Ireland	Cork University Hospital	Cork
Ireland	St James Hospital	Dublin
Ireland	Mater Misercordiae Hospital	Dublin 7
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Organization	Jerusalem
Israel	Meir Medical Center	Kfar-Saba
Israel	Tel-Aviv Sourasky Medical Center	Tel-Aviv	Tel Aviv
Israel	Shamir Medical Center - Assaf Harofeh	Zerifin
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	IRCCS - Istituto Romagnolo per lo Studio Dei Tumori "Dino Amadori" (IRST)	Meldola (fc)	Fc
Italy	Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera Universitaria Federico Ii	Napoli Campania
Italy	A.O.U. Maggiore della Carit	Novara
Italy	Azienda Ospedaliera Di Padova	Padova
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli	Reggio Di Calabria
Italy	Azienda Ospedaliera Sant Andrea	Roma
Italy	Azienda Policlinico Universitario Umberto I	Roma
Italy	Ospedale S Eugenio	Roma
Italy	Local Institution - 245	Terni
Italy	A.O.U. Citta Della Salute E Della Scienza , Presidio Molinette,S.C. Ematologia Universitaria	Torino
Italy	Universita degli Studi dell'Insubria - Ospedale di Circolo e Fondazione Macchi - Varese	Varese
Italy	Centro Ricerche Cliniche di Verona S.r.l.	Verona
Japan	Aomori Prefectural Central Hospital	Aomori
Japan	Juntendo University Hospital	Bunkyo-ku	Tokyo
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	Shonan Kamakura General Hospital	Kamakura
Japan	Kameda General Hospital	Kamogawa
Japan	Local Institution - 706	Maebashi
Japan	University of Miyazaki Hospital	Miyazaki
Japan	The Japanese Red Cross Nagasaki Genbaku Hospital	Nagasaki-shi	Nagasaki
Japan	Ogaki Municipal Hospital	Ogaki
Japan	Osaka Metropolitan university Hospital	Osaka
Japan	Kindai University Hospital- Osakasayama Campus	Osakasayama	Osaka
Japan	Local Institution - 708	Sapporo
Japan	NTT Medical Center Tokyo	Shinagawa-ku, Tokyo
Japan	Tokyo Women's Medical University Hospital	Shinjuku City
Japan	Local Institution - 710	Shinjyuku-ku
Japan	Toyohashi Municipal Hospital	Toyohashi
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun-Gun
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea Seoul - Saint Mary's Hospital	Seoul
Lebanon	American Univ of Beirut Med Center	Badaro Beirut
Lebanon	LAU Medical Center Rizk Hospital	Beirut
Lebanon	Hammoud Hospital University Medical Center	Saida	South
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie	Krakow
Poland	Wojewódzki Szpital Specjalistyczny im. M. Kopernika w Lodzi	Lodz
Poland	ALVAMED	Poznan
Poland	Specjalistyczny Szpital im. dra Alfreda Sokolowskiego	Walbrzych
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu	Wroclaw
Romania	Onco Card SRL	Brasov
Romania	Fundeni Clinical Institute	Bucharest
Romania	Prof. Dr. I. Chiricuta Institute of Oncology	Cluj-Napoca
Romania	Spitalul Clinic Municipal Filantropia Craiova	Craiova	Dolj
Russian Federation	Local Institution - 500	Moscow
Russian Federation	Local Institution - 502	St Petersburg
Russian Federation	Local Institution - 503	St. Petersburg
Spain	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 De Gran Canaria Dr. Negrin	Las Palmas de Gran Canaria
Spain	Hospital Universitario 12 De Octubre	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Local Institution - 202	Palma de Mallorca
Spain	Universitario de Salamanca - Hospital Clinico	Salamanca
Spain	Complejo Hospitalario Universitario De Santiago	Santiago de Compostela
Spain	Hospital Universitario Virgen del Rocio	Seville
Spain	Hospital Clinico Universitario De Valencia	Valencia
United Kingdom	Heart of England NHS Foundation Trust	Birmingham
United Kingdom	United Lincolnshire Hospitals NHS Trust	Boston
United Kingdom	Nottingham City Hospital	Nottingham	Nottinghamshire
United Kingdom	Churchhill Hospital	Oxford
United States	Local Institution - 114	Ann Arbor	Michigan
United States	Local Institution - 112	Chicago	Illinois
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	The University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	University Of Kentucky Markey Cancer Center	Lexington	Kentucky
United States	University Of California Los Angeles	Los Angeles	California
United States	Mount Sinai Medical Center	New York	New York
United States	Local Institution - 135	Orlando	Florida
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	University of Pittsburg Medical Center	Pittsburgh	Pennsylvania
United States	BRCR Medical Center Inc.	Plantation	Florida
United States	Local Institution - 108	Saint Louis	Missouri
United States	University of Utah - Huntsman Cancer Institute	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Chile,  China,  Colombia,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Lebanon,  Poland,  Romania,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Red blood cell-transfusion independence (RBC-TI) = 12 weeks (RBC-TI 12)	Proportion of subjects who become RBC-transfusion free over any consecutive 12-week period starting within the first 24 weeks.	Up to 24 weeks
Secondary	Red blood cell-transfusion independence = 16 weeks (RBC-TI 16)	Proportion of subjects who become RBC-transfusion free over any consecutive 16-week period	Up to 24 weeks
Secondary	Duration of Red blood cell-transfusion independence (RBC-TI 12)	Maximum duration of RBC-TI response	Up to end of treatment, approximately 3 years
Secondary	Reduction of transfusion burden by = 50% and by = 4 units/12 weeks from baseline over any consecutive 12-week period	Proportion of subjects who reduce their transfusion burden by = 50% and by = 4 units/12 weeks from baseline over any consecutive 12-week period	Up to 24 weeks
Secondary	Duration of reduction in transfusion burden	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	Up to end of treatment, approximately 3 years
Secondary	Red blood cell-transfusion independence = 12 weeks in the treatment period (RBC-TI 12/TP)	Proportion of subjects who become RBC-transfusion free over any consecutive 12-week period	Up to end of treatment, approximately 3 years
Secondary	Red blood cell-transfusion independence = 16 weeks in the treatment period (RBC-TI 16/TP)	Proportion of subjects who become RBC-transfusion free over any consecutive 16-week period	Up to end of treatment, approximately 3 years
Secondary	Change in RBC transfusion burden	Mean change in transfusion burden (RBC units) from baseline	Up to 24 weeks
Secondary	Cumulative duration of RBC-transfusion independence	Cumulative response duration for subjects achieving multiple episodes of RBC-TI 12	Up to end of treatment, approximately 3 years
Secondary	Mean Hgb increase = 1 g/dL from baseline over any consecutive 12-week period in absence of RBC transfusions	Proportion of subjects achieving a 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
Secondary	Change in serum ferritin from baseline	Change in serum ferritin	Up to end of treatment, approximately 3 years
Secondary	Incidence of Adverse Events (AEs)	Number of participants with adverse events	From screening up to 42 days post last dose
Secondary	Transformation to blast phase: Number of subjects who transform into AML	AML = acute myeloid leukemia	Up to approximately 5 years
Secondary	Frequency of Antidrug antibodies (ADA)	Will be collected for assessment of anti-drug antibodies (ADA) against Luspatercept in serum in all subjects	From randomization and up to including 48 weeks post first dose
Secondary	Pharmacokinetics - Area Under the Concentration-Time Curve (AUC)	Measures of luspatercept exposure area under the curve	From randomization and up to including 48 weeks post first dose
Secondary	Pharmacokinetics - Maximum plasma concentration of drug (Cmax)	Maximum plasma concentration of drug	From randomization and up to including 48 weeks post first dose

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting