AzTrials
AzTrials

Myeloproliferative DisordersPhase 3INDEPENDENCENCT04717414

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

A Phase 3 study testing ACE-536 in people with Myeloproliferative Disorders and Myelofibrosis, run by Celgene at 185 sites in 26 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ACE-536
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
313 participants
Where
185 sitesin 26 countries
Study dates
25 Feb 2021to 18 Aug 2032
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:.
  • 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.
  • RBC transfusions are scored in determining eligibility when given for treatment of:.
  • Symptomatic (ie, fatigue or shortness of breath) anemia with a pretransfusion Hgb ≤ 9.5 g/dL or.
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  • Asymptomatic anemia with a pretransfusion Hgb ≤ 7 g/dL.
  • 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:.
  • 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.
  • 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.
  • 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.].
  • 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.

Who cannot join

  • 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.
  • 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.
  • 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:.
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  • Neutrophils: < 1 x 10^9/L.
  • White blood count (WBC): > 100 x 10^9/L.
  • 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.
  • Peripheral blood myeloblasts:> 5%.
  • 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).
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT):> 3.0 x upper limit of normal (ULN).
  • Direct bilirubin: ≥ 2 x ULN.
  • 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:.
  • Basal or squamous cell carcinoma of the skin.
  • Carcinoma in situ of the cervix.
  • Carcinoma in situ of the breast.
  • 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.

Trial locations and contacts

185 sites in 26 countries.

185 sites in 26 countries

China20 sites

  • Beijing Peking Union Medical College Hospital

    Beijing, 100730

  • Local Institution - 802

    Changchun, 130021

  • Xiangya Hospital Central-South University

    Changsha, Hunan, 410008

  • Nanfang Hospital of Southern Medical University

    Guangzhou, GD, 510515

  • Guangdong General Hospital

    Guangzhou, 510030

  • The First Affiliated Hospital Of Harbin Medical University

    Harbin, 150081

  • The Second Affiliated Hospital Of Kunming Medical University

    Kunming, Yunnan, 650101

  • Local Institution - 820

    Nanchang, Jiangxi, 330006

  • Nanchang University - The Second Affiliated Hospital

    Nanchang, Jiangxi, 330008

  • Local Institution - 804

    Nanjing, Jiangsu, 210029

  • Local Institution - 818

    Nantong, Jiangsu, 226001

  • The First Affiliated Hospital of Nanyang Medical College

    Nanyang, Henan

  • Local Institution - 821

    Qingdao, Shandong, 0

  • Local Institution - 809

    Shanghai, 200025

  • Local Institution - 801

    Shanghai, 200233

  • Local Institution - 811

    Suzhou, 215006

  • Local Institution - 816

    Taiyuan, Shanxi, 030001

  • Local Institution - 800

    Tianjin, 300041

  • Tianjin Medical University General Hospital

    Tianjin, 300052

  • Local Institution - 810

    Zhengzhou, 0

Other trials in China

Italy19 sites

  • Local Institution - 250

    Ancona, 60126

  • Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi

    Bologna, 40138

  • Asst Spedali Civili Di Brescia

    Brescia, 25123

  • Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele - Ospedale Gaspare Rodolico

    Catania, 95123

  • Azienda Ospedaliera Universitaria Careggi

    Florence, 50134

  • IRCCS - Istituto Romagnolo per lo Studio Dei Tumori "Dino Amadori" (IRST)

    Meldola (fc), Fc, 47014

  • Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico

    Milan, 20122

  • Local Institution - 246

    Napoli Campania, 80131

  • A.O.U. Maggiore della Carit

    Novara, 28100

  • Azienda Ospedaliera Di Padova

    Padova, 35128

  • Local Institution - 248

    Pisa, 56100

  • Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli

    Reggio Calabria, 89124

  • Azienda Policlinico Universitario Umberto I

    Roma, 00100

  • Local Institution - 251

    Roma, 00189

  • Local Institution - 249

    Roma, 144

  • Local Institution - 245

    Terni, 05100

  • Local Institution - 259

    Torino, 10126

  • Universita degli Studi dell'Insubria - Ospedale di Circolo e Fondazione Macchi - Varese

    Varese, 21100

  • Centro Ricerche Cliniche di Verona S.r.l.

    Verona, 37134

Other trials in Italy

Japan18 sites

  • Aomori Prefectural Central Hospital

    Aomori, 030-8553

  • Local Institution - 713

    Bunkyō City, 113-8677

  • Local Institution - 701

    Bunkyo-ku, Tokyo, 113-8431

  • Local Institution - 709

    Chūō, Yamanashi, 409-3898

  • Tokai University Hospital

    Isehara City, Kanagawa, 259-1193

  • Local Institution - 717

    Kamakura, 247-8533

  • Kameda General Hospital

    Kamogawa, 296-8602

  • Local Institution - 706

    Maebashi, 371-8511

  • University of Miyazaki Hospital

    Miyazaki, 889-1692

  • The Japanese Red Cross Nagasaki Genbaku Hospital

    Nagasaki, Nagasaki, 8528511

  • Ogaki Municipal Hospital

    Ōgaki, 503-8502

  • Osaka Metropolitan university Hospital

    Osaka, 545-8586

  • Local Institution - 708

    Sapporo, 003-0006

  • Kindai University Hospital- Osakasayama Campus

    Sayama, Osaka, 5898511

  • NTT Medical Center Tokyo

    Shinagawa-ku, Tokyo, 141-8625

  • Tokyo Women's Medical University Hospital

    Shinjuku, 162-8666

  • Local Institution - 710

    Shinjyuku-ku, 160-0023

  • Toyohashi Municipal Hospital

    Toyohashi, 441-8570

Other trials in Japan

United States14 sites

  • Local Institution - 114

    Ann Arbor, Michigan, 48109

  • Local Institution - 112

    Chicago, Illinois, 60612

  • John Theurer Cancer Center

    Hackensack, New Jersey, 07601-2191

  • The University of Texas - MD Anderson Cancer Center

    Houston, Texas, 77030

  • Local Institution - 130

    Knoxville, Tennessee, 37920

  • Local Institution - 124

    Lexington, Kentucky, 40536-0293

  • Local Institution - 110

    Los Angeles, California, 90095

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Local Institution - 135

    Orlando, Florida, 32804

  • University of Pittsburg Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Allegheny Health Network

    Pittsburgh, Pennsylvania, 15224

  • Local Institution - 133

    Plantation, Florida, 33322

  • Local Institution - 119

    Salt Lake City, Utah, 84112

  • Local Institution - 108

    St Louis, Missouri, 63110

Other trials in United States

France13 sites

  • Local Institution - 331

    Angers, 49033

  • Local Institution - 333

    Clermont-Ferrand, 63000

  • Local Institution - 324

    Créteil, 94010

  • Chu De Grenoble

    Grenoble, 38043

  • Local Institution - 327

    Lille, 59037

  • Local Institution - 332

    Lyon, 69008

  • CHU de Nice Archet I

    Nice, 06202

  • Centre Hospitalier Universitaire de Nimes (CHU) - Hopital Universitaire Caremeau

    Nîmes, 30029

  • Hopital Saint Louis

    Paris, 75475

  • Groupe Hospitalier Sud Hopital Haut Leveque USN

    Pessac, 33604

  • CHU La Miletrie

    Poitiers, 86021

  • ICANS Institut de cancerologie Strasbourg Europe

    Strasbourg, 67200

  • Local Institution - 330

    Toulouse, 31059

Other trials in France

Spain11 sites

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Hospital Universitari Germans Trias i Pujol ICO Badalona

    Barcelona, 08916

  • Local Institution - 208

    Granada, 18014

  • Hospital Universitario De Gran Canaria Dr. Negrin

    Las Palmas de Gran Canaria, 35012

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Universitario 12 De Octubre

    Madrid, 28041

  • Local Institution - 202

    Palma de Mallorca, 7120

  • Universitario de Salamanca - Hospital Clinico

    Salamanca, 37007

  • Complejo Hospitalario Universitario De Santiago

    Santiago de Compostela, 15706

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital Clinico Universitario De Valencia

    Valencia, 46010

Other trials in Spain

Germany9 sites

  • Unviversitatsklinikum Aachen

    Aachen, 52074

  • Stauferklinikum Schwab. Gmund

    Baden-Warttemberg, 73557

  • Local Institution - 299

    Düsseldorf, 40225

  • Universitatsklinikum Halle Saale

    Halle, 06120

  • Local Institution - 300

    Hamburg, 22081

  • Universitaetsklinikum Jena

    Jena, 07740

  • Local Institution - 297

    Leipzig, 04103

  • Local Institution - 301

    Mannheim, 68167

  • Johannes Wiesling Klinikum Minden

    Minden, 32429

Other trials in Germany

Belgium8 sites

  • Local Institution - 318

    Bruges, 8000

  • Local Institution - 312

    Brussels, 1200

  • Local Institution - 313

    Hasselt, 3500

  • Uz Leuven

    Leuven, 3000

  • Local Institution - 319

    Liège, 4000

  • Local Institution - 316

    Roeselare, 8800

  • Local Institution - 315

    Verviers, 4800

  • Cliniques Universitaires UCL de Mont-Godine

    Yvoir, 5530

Other trials in Belgium

Canada8 sites

  • Local Institution - 181

    Calgary, Alberta, T2N 4N2

  • Local Institution - 179

    Edmonton, Alberta, T6G 2S2

  • University Hospital - London Health Sciences Centre

    London, Ontario, N6C 6B5

  • Local Institution - 177

    Montreal, Quebec, H1T 2M4

  • Sir Mortimer B. Davis - Jewish Genl

    Montreal, Quebec, H3T 1E2

  • Local Institution - 176

    Sherbrooke, Quebec, J1H5N4

  • Local Institution - 180

    Toronto, Ontario, M5G 2M9

  • Local Institution - 183

    Vancouver, British Columbia, V6Z 2A5

Other trials in Canada

Greece7 sites

  • Local Institution - 383

    Alexandroupoli, 08100

  • Evangelismos General Hospital of Athens

    Athens, 10676

  • Local Institution - 386

    Athens, 11 527

  • Attikon University General Hospital

    Athens, 12464

  • Local Institution - 387

    Pátrai, Achaia, 264 43

  • University General Hospital of Patras

    Rio Patras, 26500

  • Georgios Papanikolaou General Hospital of Thessaloniki

    Thessaloniki, 57010

Other trials in Greece

South Korea7 sites

  • Kyungpook National University Hospital

    Daegu, 700-721

  • Chonnam National University Hwasun Hospital

    Hwasun-Gun, 58128

  • Local Institution - 643

    Seongnam-si, 13620

  • Local Institution - 647

    Seoul, 06351

  • The Catholic University of Korea Seoul - Saint Mary's Hospital

    Seoul, 06591

  • Seoul National University Hospital

    Seoul, 3080

  • Asan Medical Center

    Seoul, 5505

Other trials in South Korea

Poland6 sites

  • Local Institution - 436

    Gdansk, 80-952

  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie

    Krakow, 31-501

  • Wojewódzki Szpital Specjalistyczny im. M. Kopernika w Lodzi

    Lodz, 93-510

  • Local Institution - 433

    Poznan, 61-696

  • Specjalistyczny Szpital im. dra Alfreda Sokolowskiego

    Wałbrzych, 58-309

  • Local Institution - 435

    Wroclaw, 50367

Other trials in Poland

Australia5 sites

  • Monash Medical Centre

    Clayton, Victoria, 3168

  • Gosford Hospital

    Gosford, 2250

  • Royal Hobart Hospital

    Hobart, 7000

  • The Alfred Hospital

    Melbourne, Victoria, 3004

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

Other trials in Australia

Israel5 sites

  • Rambam Medical Center

    Haifa, 31096

  • Hadassah Medical Organization

    Jerusalem, 91120

  • Meir Medical Center

    Kfar Saba, 44281

  • Tel-Aviv Sourasky Medical Center

    Tel Aviv, Tel Aviv, 64239

  • Shamir Medical Center - Assaf Harofeh

    Tsrifin, 70300

Other trials in Israel

Austria4 sites

  • Local Institution - 272

    Graz, 8036

  • Krankenhaus der Elisabethinen Linz, I Interne Abteilung

    Linz, 4020

  • Local Institution - 271

    Vienna, 1090

  • Local Institution - 274

    Vienna, 1140

Other trials in Austria

Romania4 sites

  • Onco Card SRL

    Brasov, 500052

  • Local Institution - 391

    Bucharest, 022328

  • Prof. Dr. I. Chiricuta Institute of Oncology

    Cluj-Napoca, 400015

  • Local Institution - 395

    Craiova, Dolj, 200143

Other trials in Romania

United Kingdom4 sites

  • Heart of England NHS Foundation Trust

    Birmingham, B9 5SS

  • United Lincolnshire Hospitals NHS Trust

    Boston, PE21 9QS

  • Nottingham City Hospital

    Nottingham, Nottinghamshire, NG5 1PB

  • Churchhill Hospital

    Oxford, OX3 7LI

Other trials in United Kingdom

Argentina3 sites

  • Hospital Italiano de Buenos Aires

    Buenos Aires, C1199ABB

  • Local Institution - 172

    Ciudad Autónoma de BuenosAires, Buenos Aires, C1280AEB

  • Hospital Italiano de La Plata

    La Plata, Buenos Aires, B1900AX

Other trials in Argentina

Chile3 sites

  • IC La Serena Research

    La Serena, Coquimbo Region, 1720430

  • Local Institution - 192

    Las Condes, Metropolitana de Santiago, 7560742

  • Local Institution - 193

    Santiago, 7500587

Other trials in Chile

Colombia3 sites

  • Local Institution - 163

    Bogotá, Distrito Capital de Bogotai, 111511

  • Local Institution - 162

    Floridablanca, Soto, 681002

  • Local Institution - 161

    Medellín, Antioquia, 50034

Other trials in Colombia

Ireland3 sites

  • Cork University Hospital

    Cork, T12 DFK4

  • Mater Misercordiae Hospital

    Dublin, 7

  • St James Hospital

    Dublin, Dublin 8

Other trials in Ireland

Lebanon3 sites

  • Local Institution - 550

    Badaro Beirut, 11072280

  • Local Institution - 552

    Beirut, 11-3288

  • Local Institution - 551

    Saida, South, 652

Other trials in Lebanon

Russia3 sites

  • Local Institution - 500

    Moscow, 125284

  • Local Institution - 503

    Saint Petersburg, 197022

  • Local Institution - 502

    Saint Petersburg, 197341

Other trials in Russia

Hong Kong2 sites

  • Local Institution - 661

    Hong Kong, 0

  • Prince of Wales Hospital the Chinese University of Hong Kong

    Shatin, 0

Other trials in Hong Kong

Hungary2 sites

  • Local Institution - 462

    Budapest, 1096

  • Local Institution - 463

    Győr, 9023

Other trials in Hungary

Czechia1 site

  • Local Institution - 341

    Prague, 128 08

Other trials in Czechia

About this study

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

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.

Read the 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
Being tested
ACE-536, Placebo
Keywords
Luspatercept, ACE-536, Myeloproliferative Neoplasm, Myelofibrosis, JAK2, Red blood cell transfusion, Post-ET MF, Post-PV MF, Reblozyl, Anemia
Medical subject headings
Myeloproliferative Disorders, Primary Myelofibrosis, Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ACE-536Drug

    Also called Luspatercept, BMS-986346

    Subcutaneous Injection

  • PlaceboOther

    Subcutaneous Injection

Study groups in NCT04717414
Study groupRoleWhat they receive
Experimental Arm: Luspatercept (ACE-536)ExperimentalLuspatercept will be given to participants via subcutaneous injection (administered on Day 1 of each 21-day treatment cycle)
Receives: Drug: ACE-536
Control Arm: PlaceboPlacebo comparatorPlacebo starting dose with volume equivalent to experimental arm subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle)
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Red Blood Cell-transfusion Independence (RBC-TI) ≥ 12 Weeks (RBC-TI 12)

    Percentage of participants who become RBC-transfusion free over any consecutive 12-week period starting in first 24 weeks.

    Measured: From randomization to week 36 (Approximately 36 Weeks)

Secondary outcomes (14)

  1. Red Blood Cell-transfusion Independence (RBC-TI) ≥ 16 Weeks (RBC-TI 16)

    Percentage of participants who become RBC-transfusion free over any consecutive 16-week period starting in first 24 weeks.

    Measured: From randomization to week 40 (Approximately 40 Weeks)

  2. Observed Duration of Response of RBC-TI 12

    Maximum observed duration of response of RBC-TI 12

    Measured: From randomization to data cutoff date (Approximately 48.92 Months)

  3. Reduction in Transfusion Burden

    Percentage of participants who reduce their transfusion burden by ≥ 50% and by ≥ 4 units/12 weeks from baseline over any consecutive 12- week period. Starting in first 24 weeks.

    Measured: Randomization up to week 36 (Approximately week 36)

  4. 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

    Measured: Randomization up to data cutoff date (Approximately 48.92 Months)

  5. RBC-TI ≥ 12 Weeks in Treatment Period (RBC-TI 12/TP)

    Percentage of participants who become RBC-transfusion free over any consecutive 12-week period.

    Measured: Randomization up to end of blinded treatment period (Approximately 209 Weeks)

  6. RBC-TI ≥ 16 Weeks in Treatment Period (RBC-TI 16/TP)

    Percentage of participants who become RBC-transfusion free over any consecutive 16-week period.

    Measured: Randomization up to end of blinded treatment period (Approximately 209 Weeks)

  7. Change in RBC Transfusion Burden

    Mean change in transfusion burden (RBC units) from baseline

    Measured: Randomization up to and including Week 24

  8. Observed Cumulative Duration of RBC-transfusion Independence

    Observed cumulative response duration for participants achieving multiple episodes of RBC-TI 12

    Measured: Randomization up to data cutoff date. (Approximately 48.92 months)

  9. Mean Hemoglobin (Hgb) Increase ≥ 1 g/dL

    Percentage of participants achieving a mean Hgb increase ≥ 1 g/dL from baseline over any consecutive 12- week period in absence of RBC transfusions

    Measured: Randomization up to week 36 (approximately 36 weeks) and end of treatment (Approximately 209 weeks)

  10. Median Change in Serum Ferritin From Baseline

    Median change in serum ferritin from baseline

    Measured: Randomization to Day 169, and to end of treatment (approximately 209 weeks)

  11. Relationship of Adverse Events to Luspatercept and Placebo

    Frequencies of adverse events according to adverse events categories

    Measured: First dose up to 42 days post last dose (Approximately 215 weeks)

  12. Transformation to Blast Phase

    Number and percentage of participants who transform to blast phase

    Measured: Randomization up to data cutoff date. (Approximately 48.92 months)

  13. Number of Participants With ADA Measurement

    Number of participants with positive or negative ADA Measurement

    Measured: From randomization up to 48 weeks post first dose (approximately 48 weeks)

  14. Trough Serum Concentration of Luspatercept at Day 169

    Trough Serum concentration of luspatercept at day 169

    Measured: from first dose to day 169

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jan 2021
  2. Study start25 Feb 2021
  3. Primary completion26 May 2025
  4. Study completion18 Aug 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
313 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04717414
Sponsor's protocol ID
ACE-536-MF-002
Other IDs
2020-000607-36, U1111-1260-9595
Acronym
INDEPENDENCE
Status last verified
Jun 2026
First submitted
29 Dec 2020
Last updated
16 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ACE-536 in people with Myeloproliferative Disorders and Myelofibrosis, run by Celgene at 185 sites in 26 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 185 sites in China, Italy, Japan, United States, France and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Red Blood Cell-transfusion Independence (RBC-TI) ≥ 12 Weeks (RBC-TI 12) (time frame: From randomization to week 36 (Approximately 36 Weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04717414.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2026.

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