A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials

NCT04064060 | Recruiting Phase 3 FDA Drug

• 3 other identifiers: ACE-536-LTFU-001U1111-1235-81232022-502498-40
• Study Type: interventional
• Target: 665
• Locations: 21 countries
• Sites: 137

Brief Summary

A Phase 3b, open-label, single-arm, rollover study to evaluate the long-term safety of luspatercept, to the following participants:

• Participants receiving luspatercept on a parent protocol at the time of their transition to the rollover study, who tolerate the protocol-prescribed regimen in the parent trial and, in the opinion of the investigator, may derive clinical benefit from continuing treatment with luspatercept
• Participants in the follow-up phase previously treated with luspatercept or placebo in the parent protocol will continue into long-term post-treatment follow-up in the rollover study until the follow-up commitments are met
• The study design is divided into the Transition Phase, Treatment Phase and Follow-up Phase. Participants will enter transition phase and depending on their background will enter either the treatment phase or the Long-term Post-treatment Follow-up (LTPTFU) phase
• Transition Phase is defined as one Enrollment visit
• Treatment Phase: For participants in luspatercept treatment the dose and schedule of luspatercept in this study will be the same as the last dose and schedule in the parent luspatercept study. This does not apply to participants that are in long-term follow-up from the parent protocol
• Follow-up Phase includes: \- 42 Day Safety Follow-up Visit
• During the Safety Follow up, the participants will be followed for 42 days after the last dose of luspatercept, for the assessment of safety-related parameters and adverse event (AE) reporting \- Long-term Post-treatment Follow-up (LTPTFU) Phase
• Participants will be followed for overall survival every 6 months for at least 5 years from first dose of luspatercept in the parent protocol, or 3 years of post-treatment from last dose, whichever occurs later, or until death, withdrawal of consent, study termination, or until a subject is lost to follow-up. Participants will also be monitored for progression to AML or any malignancies/pre-malignancies. New anticancer or disease related therapies should be collected at the same time schedule Participants transitioning from a parent luspatercept study in post-treatment follow-up (safety or LTPTFU) will continue from the same equivalent point in this rollover study. The ACE-536-LTFU-001 rollover study will be terminated, and relevant participants will discontinue from the study when all participants fulfill 5 years on the study, including treatment and follow-up.

Conditions

Myelodysplastic Syndromes (MDS); Beta-thalassemia; Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis

Keywords

ACE-536; Luspatercept; MDS; Beta-thalassemia; Myeloproliferative neoplasm (MPN)-associated myelofibrosis

Outcome Measures

Primary Outcomes (5)

• Adverse Events (AEs)

  Type, frequency, severity of AEs, relationship of treatment emergent adverse events to luspatercept

  From enrollment until at least 42 Day Safety Follow-up Phase

• Number of participants progressing to high/very high risk MDS or AML.

  Progression to high/very high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) (MDS and myelofibrosis \[MF\] only).

  Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)

• Percentage of participants progressing to high/very high risk MDS or AML

  Progression to high/very high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) (MDS and myelofibrosis \[MF\] only)

  Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)

• Number of participants developing other malignancies/pre-malignancies

  Development of other malignancies/pre-malignancies

  Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)

• Percentage of participants developing other malignancies/pre-malignancies

  Development of other malignancies/pre-malignancies

  Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)

Secondary Outcomes (3)

• Overall Survival

  Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)

• Number of participants developing treatment emergent extramedullary hematopoiesis (EMH) masses

  Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)

• Percentage of participants developing treatment emergent EMH masses

  Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)

Study Arms (1)

ACE-536

EXPERIMENTAL

Luspatercept will be administered as a subcutaneous (SC) injection to participants by the study staff at the clinical site and administration will be documented in the subject's source record.

Drug: Luspatercept

Interventions

Luspatercept DRUG

Luspatercept (ACE-536), an erythroid maturation agent, is a recombinant fusion protein consisting of a modified form of the extracellular domain (ECD) of the human activin receptor type IIB (ActRIIB) linked to the human immunoglobin G 1 (IgG1) Fc domain. ActRIIB receptor and its ligands are members of the transforming growth factor-β (TGF-β) superfamily. Members of the TGF-β superfamily ligands, through their binding to activin receptors, are involved in modulating the differentiation of late-stage erythrocyte precursors (normoblasts) in the bone marrow. Luspatercept for injection is formulated as a sterile, preservative-free, lyophilized cake/powder. Luspatercept for injection is available in 25 mg and 75 mg vials and when reconstituted with water for injection, each consists of 50 mg/mL luspatercept in a 10 mM citrate buffer-based solution

Also known as: ACE-536

ACE-536

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all the following criteria to be enrolled in this study:
• Participant is ≥ 18 years at the time of signing the informed consent form (ICF).
• Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
• Participant has been participating in a luspatercept trial and continues to fulfill all the requirements of the parent protocol and the participant has been either:
• Assigned to luspatercept treatment, continues to receive clinical benefit in the opinion of the investigator and should continue to receive luspatercept treatment, OR
• Assigned to placebo arm in the parent protocol (at the time of unblinding or in follow-up) and should cross over to luspatercept treatment, OR
• Assigned to the Follow-up Phase of the parent protocol, previously treated with luspatercept or placebo in the parent protocol who shall continue into LTPTFU phase in the rollover study until the follow-up commitments are met (unless requirements are met as per parent protocol to crossover to luspatercept treatment).
• Participant understands and voluntarily signs an informed consent document prior to any study-related assessments or procedures being conducted.
• Participant demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.
• Applies to on treatment Participants only- females of childbearing potential (FCBP) defined as a sexually mature woman who:
• \) 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 or amenorrhea due to other medical reasons does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) must:
• Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the participant practices true abstinence from heterosexual contact.
• Agrees to use, and be able to comply with highly effective, contraception without interruption, 35 days prior to starting investigational product (IP), during the study therapy (including dose interruptions), and for 84 days after discontinuation of study therapy.
• \. Applies to on treatment participants only- Male participants must:
• a. Agrees 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 84 days following investigational product discontinuation even if he has undergone a successful vasectomy.

You may not qualify if:

• The presence of any of the following will exclude a participant from enrollment:
• Applies to on treatment participants only- Concomitant use of any medications/procedures that are prohibited in the parent luspatercept protocol.
• Participant has met one or more criteria for study discontinuation as stipulated in the parent luspatercept protocol.
• Applies to on treatment participants only- More than 26 days between last luspatercept dose in the parent protocol and first dose into ACE-536-LTFU-001 protocol unless dose delay or dose discontinuation criteria met.
• Applies to on treatment participants only- Pregnant or breastfeeding females.
• Participant has 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.
• Participant has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Participant has any condition that confounds the ability to interpret data from the study.

Sponsors & Collaborators

• Celgene: lead

Study Sites (143)

Childrens Hospital Los Angeles RHU

Los Angeles, California, 90027-6062, United States

RECRUITING

Local Institution - 971

Oakland, California, 94609, United States

COMPLETED

Local Institution - 978

Stanford, California, 94305, United States

COMPLETED

Local Institution - 975

Tampa, Florida, 33612, United States

COMPLETED

Local Institution - 970

Chicago, Illinois, 60611, United States

COMPLETED

Local Institution - 973

Boston, Massachusetts, 02115, United States

COMPLETED

Local Institution - 961

Detroit, Michigan, 48201, United States

COMPLETED

Local Institution - 969

New York, New York, 10065, United States

COMPLETED

Local Institution - 967

Cleveland, Ohio, 44195, United States

ACTIVE NOT RECRUITING

Local Institution - 972

Philadelphia, Pennsylvania, 19104, United States

COMPLETED

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, 37232-5505, United States

WITHDRAWN

The University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

WITHDRAWN

Local Institution - 100

South Brisbane, Queensland, 4101, Australia

COMPLETED

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Local Institution - 102

Clayton, Victoria, 3168, Australia

COMPLETED

Royal Prince Alfred Hospital

Camperdown, 2050, Australia

RECRUITING

Local Institution - 182

Brasschaat, 2930, Belgium

COMPLETED

Local Institution - 180

Bruges, 8000, Belgium

COMPLETED

Local Institution - 183

Ghent, 9000, Belgium

COMPLETED

Local Institution - 184

Leuven, 3000, Belgium

COMPLETED

Local Institution - 220

Boulevard, Sofia, 1797, Bulgaria

COMPLETED

Local Institution - 221

Plovdiv, 4002, Bulgaria

COMPLETED

Local Institution - 262

Toronto, Ontario, M4N 3M5, Canada

COMPLETED

Local Institution - 260

Toronto, Ontario, M5G 2C4, Canada

COMPLETED

Local Institution - 263

Toronto, Ontario, M5G 2M9, Canada

COMPLETED

Local Institution - 131

Beijing, Beijing Municipality, 100730, China

WITHDRAWN

Local Institution - 135

Guangzhou, Guangdong, 510515, China

WITHDRAWN

Local Institution - 132

Shanghai, Shanghai Municipality, 200233, China

WITHDRAWN

Local Institution - 134

Chengdu, Sichuan, 610041, China

WITHDRAWN

Local Institution - 130

Tianjin, Tianjin Municipality, 300020, China

WITHDRAWN

Local Institution - 133

Hangzhou, Zhejiang, 310009, China

WITHDRAWN

Local Institution - 305

Angers, 49033, France

COMPLETED

Local Institution - 300

Créteil, 94010, France

COMPLETED

Local Institution - 310

La Tronche, 38700, France

COMPLETED

Local Institution - 306

Lille, 59037, France

COMPLETED

Local Institution - 301

Marseille, 13385, France

COMPLETED

Local Institution - 302

Paris, 75010, France

COMPLETED

Local Institution - 307

Pessac, 33604, France

WITHDRAWN

Local Institution - 304

Pierre-Bénite, 69495, France

COMPLETED

Local Institution - 308

Strasbourg, 67091, France

COMPLETED

Local Institution - 309

Toulouse, 31059, France

COMPLETED

Local Institution - 303

Tours, 37044, France

WITHDRAWN

Local Institution - 341

Berlin, 14195, Germany

COMPLETED

Local Institution - 348

Dresden, 01307, Germany

COMPLETED

Local Institution - 345

Düsseldorf, 40225, Germany

COMPLETED

Local Institution - 346

Düsseldorf, 40479, Germany

COMPLETED

Local Institution - 343

Halle, 06120, Germany

COMPLETED

Local Institution - 342

Hamburg, 22081, Germany

COMPLETED

Local Institution - 344

Hanover, 30625, Germany

COMPLETED

Local Institution - 349

Leipzig, 04103, Germany

WITHDRAWN

Local Institution - 340

Mainz, 55131, Germany

COMPLETED

Local Institution - 347

München, 81675, Germany

COMPLETED

Aghia Sophia' Children's General Hospital of Athens

Athens, 115 27, Greece

RECRUITING

Laiko General Hospital of Athens - Center of Thalassemia

Athens, 115 27, Greece

RECRUITING

Local Institution - 384

Athens, 11527, Greece

COMPLETED

Local Institution - 383

Rio Patras, 26500, Greece

COMPLETED

Local Institution - 381

Thessaloniki, 54642, Greece

COMPLETED

Local Institution - 425

Afula, 1834111, Israel

COMPLETED

Local Institution - 420

Haifa, 3109601, Israel

COMPLETED

Local Institution - 422

Jerusalem, 91031, Israel

COMPLETED

Local Institution - 424

Jerusalem, 91120, Israel

COMPLETED

Local Institution - 421

Nahariya, 22100, Israel

COMPLETED

Local Institution - 423

Petah Tikva, 49100, Israel

COMPLETED

Local Institution - 478

Florence, Tuscany, 50134, Italy

ACTIVE NOT RECRUITING

Local Institution - 471

Florence, Tuscany, 50139, Italy

ACTIVE NOT RECRUITING

Local Institution - 470

Allessandria, 15100, Italy

COMPLETED

Local Institution - 464

Bologna, 40138, Italy

COMPLETED

Local Institution - 466

Brindisi, 72100, Italy

COMPLETED

Local Institution - 477

Cagliari, 09121, Italy

COMPLETED

Local Institution - 462

Ferrara, 44124, Italy

COMPLETED

Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite

Genoa, 16128, Italy

RECRUITING

Local Institution - 473

Lecce, 73100, Italy

COMPLETED

Maggiore Polyclinic Hospital, IRCCS Ca' Granda

Milan, 20122, Italy

RECRUITING

Local Institution - 479

Modena, 41124, Italy

COMPLETED

AORN A Cardarelli

Napoli, 80131, Italy

RECRUITING

AOU dell'Universita degli Studi della Campania Luigi Vanvitelli

Napoli, 80131, Italy

RECRUITING

Azienda Ospedaliero Universitaria S. Luigi Gonzaga

Orbassano, 10043, Italy

RECRUITING

Local Institution - 469

Pavia, 27100, Italy

COMPLETED

Local Institution - 468

Reggio Calabria, 89124, Italy

COMPLETED

Local Institution - 465

Roma, 133, Italy

COMPLETED

Local Institution - 474

Rozzano, 20089, Italy

WITHDRAWN

Local Institution - 472

Varese, 21100, Italy

COMPLETED

Local Institution - 463

Verona, 37134, Italy

COMPLETED

Local Institution - 610

Nagoya, Aichi-ken, 460-0001, Japan

COMPLETED

Local Institution - 601

Kamogawa, Chiba, 296-0041, Japan

COMPLETED

Matsuyama Red Cross Hospital

Matsuyama, Ehime, 790-8524, Japan

RECRUITING

Ogaki Municipal Hospital

Ōgaki, Gifu, 503-8502, Japan

RECRUITING

Japanese Red Cross Society Himeji Hospital

Himeji, Hyōgo, 6708540, Japan

RECRUITING

Local Institution - 605

Hitachi, Ibaraki, 317-0077, Japan

ACTIVE NOT RECRUITING

Kitasato University Hospital

Sagamihara, Kanagawa, 252-0329, Japan

RECRUITING

Local Institution - 0979

Sendai, Miyagi, 980-8574, Japan

WITHDRAWN

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

RECRUITING

Local Institution - 611

Nagasaki, Nagasaki, 8528511, Japan

WITHDRAWN

Japanese Red Cross Medical Center

Shibuya City, Tokyo, 150-8935, Japan

RECRUITING

NTT Medical Center Tokyo

Shinagawa City, Tokyo, 141-8625, Japan

RECRUITING

Local Institution - 612

Chiba, 260-0852, Japan

COMPLETED

Shonan Kamakura General Hospital

Kamakura, 247-8533, Japan

RECRUITING

Osaka Metropolitan University Hospital

Osaka, 545-8586, Japan

RECRUITING

Local Institution - 604

Osaka, 589-8511, Japan

ACTIVE NOT RECRUITING

Chronic Care Center

Hazmiyeh, 00961, Lebanon

RECRUITING

Local Institution - 545

Johor Bahru, Johor, 80100, Malaysia

COMPLETED

Hospital Sultanah Bahiyah

Alor Star, Kedah, 05460, Malaysia

RECRUITING

University Malaya Medical Centre

Kuala Lumpur, Kuala Lumpur, 59100, Malaysia

RECRUITING

Hospital Raja Permaisuri Bainun

Ipoh, Perak, 30990, Malaysia

RECRUITING

Queen Elizabeth Hospital

Kota Kinabalu, Sabah, 88586, Malaysia

RECRUITING

Hospital Umum Sarawak

Kuching, Sarawak, 93586, Malaysia

RECRUITING

Local Institution - 580

Amsterdam, 1081 HV, Netherlands

COMPLETED

Local Institution - 681

Barakaldo, 48903, Spain

COMPLETED

Local Institution - 686

Barcelona, 08908, Spain

COMPLETED

Local Institution - 685

Barcelona, 8035, Spain

COMPLETED

Local Institution - 687

Madrid, 28028, Spain

COMPLETED

Local Institution - 682

Oviedo, 33011, Spain

COMPLETED

Local Institution - 684

Salamanca, 37007, Spain

COMPLETED

Local Institution - 680

Seville, 41013, Spain

COMPLETED

Local Institution - 683

Valencia, 46026, Spain

COMPLETED

Local Institution - 720

Gothenburg, 413 45, Sweden

COMPLETED

Local Institution - 722

Lund, SE-221 85, Sweden

COMPLETED

Local Institution - 721

Stockholm, 141 86, Sweden

COMPLETED

Local Institution - 760

Kaohsiung, San Ming Dist., 807, Taiwan

COMPLETED

China Medical University Hospital

Taichung, 40447, Taiwan

RECRUITING

Local Institution - 761

Taipei, 100225, Taiwan

COMPLETED

Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

RECRUITING

Siriraj Hospital Mahidol University

Bangkok, 10700, Thailand

RECRUITING

Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

RECRUITING

University Hospital Farhat Hached

Sousse, 4031, Tunisia

RECRUITING

Bone Marrow Transplant Center

Tunis, 1006, Tunisia

RECRUITING

Aziza Othmana Hospital

Tunis, 1008, Tunisia

RECRUITING

Military Hospital of Tunis

Tunis, 1008, Tunisia

RECRUITING

Local Institution - 881

Adana, 01130, Turkey (Türkiye)

COMPLETED

Local Institution - 885

Ankara, 06590, Turkey (Türkiye)

COMPLETED

Local Institution - 882

Istanbul, 34093, Turkey (Türkiye)

COMPLETED

Local Institution - 884

Istanbul, 34098, Turkey (Türkiye)

COMPLETED

Local Institution - 880

Izmir, 35100, Turkey (Türkiye)

COMPLETED

Local Institution - 883

Mersin, 33343, Turkey (Türkiye)

COMPLETED

Local Institution - 925

Aberdeen, AB25 2ZN, United Kingdom

COMPLETED

Local Institution - 921

Leeds, LS9 7TF, United Kingdom

WITHDRAWN

Local Institution - 923

London, E1 1BB, United Kingdom

COMPLETED

Whittington Hospital

London, N19 5NF, United Kingdom

RECRUITING

University College London Hospitals NHS Foundation Trust - University College Hospital

London, NW1 2BU, United Kingdom

RECRUITING

Local Institution - 928

London, SE1 9RT, United Kingdom

COMPLETED

Local Institution - 924

London, SE5 9RS, United Kingdom

COMPLETED

Local Institution - 929

Oxford, OX3 7LE, United Kingdom

WITHDRAWN

Local Institution - 926

Sutton in Ashfield, NG17 4JL, United Kingdom

WITHDRAWN

Related Links

• BMS Clinical Trial Information

MeSH Terms

Conditions

Myelodysplastic Syndromes; beta-Thalassemia; Myeloproliferative Disorders

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Central Study Contacts

BMS Study Connect Contact Center www.BMSStudyConnect.com

CONTACT

855-907-3286; Clinical.Trials@bms.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2019
• First Posted: August 21, 2019
• Study Start: August 12, 2019
• Primary Completion (Estimated): May 12, 2028
• Study Completion (Estimated): May 12, 2028
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

NL (1); ES (8); US (12); JP (16); TU (4); TW (3); MY (6); LE (1); BU (2); GR (5); SE (3); IT (20); IL (6); DE (10); AU (4); CN (6); GB (9); BE (4); TH (3); FR (11); CA (3)