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

A Phase 3b, Open-label, Single-arm, Rollover Study to Evaluate Long-term Safety in Subjects Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials

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.

Study Overview

• Status: Recruiting
• Conditions: Beta-thalassemia; Myelodysplastic Syndromes (MDS); Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis
• Intervention / Treatment: Drug: Luspatercept

• Study Type: Interventional
• Enrollment (Estimated): 665
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: First line of the email MUST contain NCT # and Site #.
• Study Contact Backup: Name: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • Recruiting
    • Royal Prince Alfred Hospital
    • Contact: Joy Ho, Site 101; Phone Number: +61295158031
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Completed
      • Local Institution - 100
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
      • Contact: Devendra Hiwase, Site 103; Phone Number: +61882223369
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Completed
      • Local Institution - 102
• Belgium
  • Brasschaat, Belgium, 2930
    • Completed
    • Local Institution - 182
  • Bruges, Belgium, 8000
    • Completed
    • Local Institution - 180
  • Ghent, Belgium, 9000
    • Completed
    • Local Institution - 183
  • Leuven, Belgium, 3000
    • Completed
    • Local Institution - 184
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • Completed
    • Local Institution - 221
  • Sofia
    • Boulevard, Sofia, Bulgaria, 1797
      • Completed
      • Local Institution - 220
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Completed
      • Local Institution - 262
    • Toronto, Ontario, Canada, M5G 2M9
      • Completed
      • Local Institution - 263
    • Toronto, Ontario, Canada, M5G 2C4
      • Completed
      • Local Institution - 260
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Withdrawn
      • Local Institution - 131
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Withdrawn
      • Local Institution - 135
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200233
      • Withdrawn
      • Local Institution - 132
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Withdrawn
      • Local Institution - 134
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Withdrawn
      • Local Institution - 130
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Withdrawn
      • Local Institution - 133
• France
  • Angers, France, 49033
    • Completed
    • Local Institution - 305
  • Créteil, France, 94010
    • Completed
    • Local Institution - 300
  • La Tronche, France, 38700
    • Completed
    • Local Institution - 310
  • Lille, France, 59037
    • Completed
    • Local Institution - 306
  • Marseille, France, 13385
    • Completed
    • Local Institution - 301
  • Paris, France, 75010
    • Completed
    • Local Institution - 302
  • Pessac, France, 33604
    • Withdrawn
    • Local Institution - 307
  • Pierre-Bénite, France, 69495
    • Completed
    • Local Institution - 304
  • Strasbourg, France, 67091
    • Completed
    • Local Institution - 308
  • Toulouse, France, 31059
    • Completed
    • Local Institution - 309
  • Tours, France, 37044
    • Withdrawn
    • Local Institution - 303
• Germany
  • Berlin, Germany, 14195
    • Completed
    • Local Institution - 341
  • Dresden, Germany, 01307
    • Completed
    • Local Institution - 348
  • Düsseldorf, Germany, 40225
    • Completed
    • Local Institution - 345
  • Düsseldorf, Germany, 40479
    • Completed
    • Local Institution - 346
  • Halle, Germany, 06120
    • Completed
    • Local Institution - 343
  • Hamburg, Germany, 22081
    • Completed
    • Local Institution - 342
  • Hanover, Germany, 30625
    • Completed
    • Local Institution - 344
  • Leipzig, Germany, 04103
    • Withdrawn
    • Local Institution - 349
  • Mainz, Germany, 55131
    • Completed
    • Local Institution - 340
  • München, Germany, 81675
    • Completed
    • Local Institution - 347
• Greece
  • Athens, Greece, 115 27
    • Recruiting
    • Aghia Sophia' Children's General Hospital of Athens
    • Contact: Antonis Kattamis, Site 382; Phone Number: +302107467772 0(000)
  • Athens, Greece, 11527
    • Completed
    • Local Institution - 384
  • Athens, Greece, 115 27
    • Completed
    • Local Institution - 380
  • Rio Patras, Greece, 26500
    • Completed
    • Local Institution - 383
  • Thessaloniki, Greece, 54642
    • Completed
    • Local Institution - 381
• Israel
  • Afula, Israel, 1834111
    • Completed
    • Local Institution - 425
  • Haifa, Israel, 3109601
    • Completed
    • Local Institution - 420
  • Jerusalem, Israel, 91031
    • Completed
    • Local Institution - 422
  • Jerusalem, Israel, 91120
    • Completed
    • Local Institution - 424
  • Nahariya, Israel, 22100
    • Completed
    • Local Institution - 421
  • Petah Tikva, Israel, 49100
    • Completed
    • Local Institution - 423
• Italy
  • Allessandria, Italy, 15100
    • Completed
    • Local Institution - 470
  • Bologna, Italy, 40138
    • Completed
    • Local Institution - 464
  • Brindisi, Italy, 72100
    • Completed
    • Local Institution - 466
  • Cagliari, Italy, 09121
    • Completed
    • Local Institution - 477
  • Ferrara, Italy, 44124
    • Completed
    • Local Institution - 462
  • Genoa, Italy, 16128
    • Recruiting
    • Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite
    • Contact: Manuela Balocco, Site 476; Phone Number: +390105634557
  • Lecce, Italy, 73100
    • Completed
    • Local Institution - 473
  • Milan, Italy, 20122
    • Recruiting
    • Maggiore Polyclinic Hospital, IRCCS Ca' Granda
    • Contact: Maria Domenica Cappellini, Site 467; Phone Number: +390250320288
  • Modena, Italy, 41124
    • Completed
    • Local Institution - 479
  • Naples, Italy, 80131
    • Recruiting
    • AORN A Cardarelli
    • Contact: Paolo Ricchi, Site 475; Phone Number: 390817472256
  • Naples, Italy, 80131
    • Recruiting
    • AOU dell'Universita degli Studi della Campania Luigi Vanvitelli
    • Contact: Silverio Perrotta, Site 461; Phone Number: +0390815665421 0 000
  • Orbassano, Italy, 10043
    • Recruiting
    • Azienda Ospedaliero Universitaria S. Luigi Gonzaga
    • Contact: Giovanni Battista Ferrero, Site 460
  • Pavia, Italy, 27100
    • Completed
    • Local Institution - 469
  • Reggio Calabria, Italy, 89124
    • Completed
    • Local Institution - 468
  • Roma, Italy, 133
    • Completed
    • Local Institution - 465
  • Rozzano, Italy, 20089
    • Withdrawn
    • Local Institution - 474
  • Varese, Italy, 21100
    • Completed
    • Local Institution - 472
  • Verona, Italy, 37134
    • Completed
    • Local Institution - 463
  • Tuscany
    • Florence, Tuscany, Italy, 50139
      • Active, not recruiting
      • Local Institution - 471
    • Florence, Tuscany, Italy, 50134
      • Completed
      • Local Institution - 478
• Japan
  • Chiba, Japan, 260-0852
    • Completed
    • Local Institution - 612
  • Kamakura, Japan, 247-8533
    • Recruiting
    • Shonan Kamakura General Hospital
    • Contact: Shuku sato, Site 613; Phone Number: +81-467-46-1717
  • Osaka, Japan, 545-8586
    • Recruiting
    • Osaka Metropolitan university Hospital
    • Contact: Yasuhiro Nakashima, Site 609
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 460-0001
      • Completed
      • Local Institution - 610
  • Chiba
    • Kamogawa, Chiba, Japan, 296-0041
      • Completed
      • Local Institution - 601
  • Ehime
    • Matsuyama, Ehime, Japan, 790-8524
      • Recruiting
      • Matsuyama Red Cross Hospital
      • Contact: Tomoaki Fujisaki, Site 606; Phone Number: 810899241111
  • Gifu
    • Ōgaki, Gifu, Japan, 503-8502
      • Recruiting
      • Ogaki Municipal Hospital
      • Contact: Hiroshi Kosugi, Site 608; Phone Number: 81584813341
  • Hyōgo
    • Himeji, Hyōgo, Japan, 6708540
      • Recruiting
      • Japanese Red Cross Society Himeji Hospital
      • Contact: Yasushi Hiramatsu, Site 614
  • Ibaraki
    • Hitachi, Ibaraki, Japan, 317-0077
      • Completed
      • Local Institution - 605
  • Kanagawa
    • Sagamihara, Kanagawa, Japan, 252-0329
      • Recruiting
      • Kitasato University Hospital
      • Contact: Takahiro Suzuki, Site 603; Phone Number: +0285587353 00000-00
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Withdrawn
      • Local Institution - 0979
    • Sendai, Miyagi, Japan, 980-8574
      • Completed
      • Local Institution - 607
  • Nagasaki
    • Nagasaki, Nagasaki, Japan, 8528511
      • Withdrawn
      • Local Institution - 611
  • Osaka
    • Sakai, Osaka, Japan, 5900197
      • Completed
      • Local Institution - 604
  • Tokyo
    • Shibuya City, Tokyo, Japan, 150-8935
      • Completed
      • Local Institution - 602
    • Shinagawa City, Tokyo, Japan, 141-8625
      • Recruiting
      • NTT Medical Center Tokyo
      • Contact: Motoshi Ichikawa, Site 600; Phone Number: 03-3448-6111
• Lebanon
  • Hazmiyeh, Lebanon, 00961
    • Recruiting
    • Chronic Care Center
    • Contact: Ali Taher, Site 500; Phone Number: +9613755669 000000.0
• Malaysia
  • Johor
    • Johor Bahru, Johor, Malaysia, 80100
      • Completed
      • Local Institution - 545
  • Kedah
    • Alor Star, Kedah, Malaysia, 05460
      • Recruiting
      • Hospital Sultanah Bahiyah
      • Contact: Hong Keng Liew, Site 542; Phone Number: 6047406191
  • Kuala Lumpur
    • Kuala Lumpur, Kuala Lumpur, Malaysia, 59100
      • Completed
      • Local Institution - 544
  • Perak
    • Ipoh, Perak, Malaysia, 30990
      • Recruiting
      • Hospital Raja Permaisuri Bainun
      • Contact: Kamini Kirubamoorthy, Site 546; Phone Number: +60193255800
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Recruiting
      • Queen Elizabeth Hospital
      • Contact: Lily Wong, Site 543; Phone Number: 6088517507
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Recruiting
      • Hospital Umum Sarawak
      • Contact: Lee Ping Chew, Site 540; Phone Number: +60165518129
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Completed
    • Local Institution - 580
• Spain
  • Barakaldo, Spain, 48903
    • Completed
    • Local Institution - 681
  • Barcelona, Spain, 08908
    • Completed
    • Local Institution - 686
  • Barcelona, Spain, 8035
    • Completed
    • Local Institution - 685
  • Madrid, Spain, 28028
    • Completed
    • Local Institution - 687
  • Oviedo, Spain, 33011
    • Completed
    • Local Institution - 682
  • Salamanca, Spain, 37007
    • Completed
    • Local Institution - 684
  • Seville, Spain, 41013
    • Completed
    • Local Institution - 680
  • Valencia, Spain, 46026
    • Completed
    • Local Institution - 683
• Sweden
  • Gothenburg, Sweden, 413 45
    • Completed
    • Local Institution - 720
  • Lund, Sweden, SE-221 85
    • Completed
    • Local Institution - 722
  • Stockholm, Sweden, 141 86
    • Completed
    • Local Institution - 721
• Taiwan
  • Kaohsiung, San Ming Dist., Taiwan, 807
    • Completed
    • Local Institution - 760
  • Taichung, Taiwan, 40447
    • Completed
    • Local Institution - 762
  • Taipei, Taiwan, 100225
    • Completed
    • Local Institution - 761
• Thailand
  • Bangkok, Thailand, 10330
    • Recruiting
    • Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital
    • Contact: Pranee Sutcharitchan, Site 800; Phone Number: +66022564564
  • Bangkok, Thailand, 10700
    • Recruiting
    • Siriraj Hospital Mahidol University
    • Contact: Vip Viprakasit, Site 802; Phone Number: 6624122113
  • Chiang Mai, Thailand, 50200
    • Recruiting
    • Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital
    • Contact: Adisak Tantiworawit, Site 801; Phone Number: +66815688875
• Tunisia
  • Sousse, Tunisia, 4031
    • Recruiting
    • University Hospital Farhat Hached
    • Contact: Khelif Abderahim, Site 840; Phone Number: +21673102503
  • Tunis, Tunisia, 1006
    • Recruiting
    • Bone Marrow Transplant Center
    • Contact: Monia Ouederni, Site 841; Phone Number: +21693184151 0000 00
  • Tunis, Tunisia, 1008
    • Recruiting
    • Aziza Othmana Hospital
    • Contact: Karima Kacem, Site 842
  • Tunis, Tunisia, 1008
    • Recruiting
    • Military Hospital of Tunis
    • Contact: Fehmi M'Sadk, Site 843; Phone Number: +21671393490
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01130
    • Completed
    • Local Institution - 881
  • Ankara, Turkey (Türkiye), 06590
    • Completed
    • Local Institution - 885
  • Istanbul, Turkey (Türkiye), 34093
    • Completed
    • Local Institution - 882
  • Istanbul, Turkey (Türkiye), 34098
    • Completed
    • Local Institution - 884
  • Izmir, Turkey (Türkiye), 35100
    • Completed
    • Local Institution - 880
  • Mersin, Turkey (Türkiye), 33343
    • Completed
    • Local Institution - 883
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Completed
    • Local Institution - 925
  • Leeds, United Kingdom, LS9 7TF
    • Withdrawn
    • Local Institution - 921
  • London, United Kingdom, E1 1BB
    • Completed
    • Local Institution - 923
  • London, United Kingdom, N19 5NF
    • Recruiting
    • Whittington Hospital
    • Contact: Emma Drasar, Site 920; Phone Number: +4402072723070
  • London, United Kingdom, NW1 2BU
    • Recruiting
    • University College London Hospitals NHS Foundation Trust - University College Hospital
    • Contact: John Porter, Site 922; Phone Number: 8076846044
  • London, United Kingdom, SE1 9RT
    • Completed
    • Local Institution - 928
  • London, United Kingdom, SE5 9RS
    • Completed
    • Local Institution - 924
  • Oxford, United Kingdom, OX3 7LE
    • Withdrawn
    • Local Institution - 929
  • Sutton in Ashfield, United Kingdom, NG17 4JL
    • Withdrawn
    • Local Institution - 926
• United States
  • California
    • Los Angeles, California, United States, 90027-6062
      • Completed
      • Local Institution - 968
    • Oakland, California, United States, 94609
      • Completed
      • Local Institution - 971
    • Stanford, California, United States, 94305
      • Completed
      • Local Institution - 978
  • Florida
    • Tampa, Florida, United States, 33612
      • Completed
      • Local Institution - 975
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Completed
      • Local Institution - 970
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Completed
      • Local Institution - 973
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Completed
      • Local Institution - 961
  • New York
    • New York, New York, United States, 10065
      • Completed
      • Local Institution - 969
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Completed
      • Local Institution - 967
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Completed
      • Local Institution - 972
  • Tennessee
    • Nashville, Tennessee, United States, 37232-5505
      • Withdrawn
      • Vanderbilt - Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Withdrawn
      • The University of Texas - MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must meet all the following criteria to be enrolled in this study:

1. Participant is ≥ 18 years at the time of signing the informed consent form (ICF).
2. Participant is willing and able to adhere to the study visit schedule and other protocol requirements.

3. 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:

   1. Assigned to luspatercept treatment, continues to receive clinical benefit in the opinion of the investigator and should continue to receive luspatercept treatment, OR
   2. 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
   3. 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).
4. Participant understands and voluntarily signs an informed consent document prior to any study-related assessments or procedures being conducted.
5. Participant demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.
6. Applies to on treatment Participants only- females of childbearing potential (FCBP) defined as a sexually mature woman 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 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:

1. 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.

2. 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.

   7. 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.

Exclusion Criteria:

The presence of any of the following will exclude a participant from enrollment:

1. Applies to on treatment participants only- Concomitant use of any medications/procedures that are prohibited in the parent luspatercept protocol.
2. Participant has met one or more criteria for study discontinuation as stipulated in the parent luspatercept protocol.
3. 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.
4. Applies to on treatment participants only- Pregnant or breastfeeding females.
5. 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.
6. 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.
7. Participant has any condition that confounds the ability to interpret data from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ACE-536; 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; 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; Other Names: ACE-536

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from date of randomization until death from any cause	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)

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Musallam KM, Cappellini MD, Kattamis A, Dyer M, Hnoosh A, Eliason L, Pelligra CG, Guo S, Mu Y, Medlin LF, Reverte M, Kuo KHM, Taher AT. Patient-Reported Outcomes With Luspatercept Through 5 Years of Treatment in Patients With Non-Transfusion-Dependent beta-Thalassemia Treated in the BEYOND Trial. Eur J Haematol. 2026 Mar 19. doi: 10.1111/ejh.70161. Online ahead of print.

Helpful Links

• BMS Clinical Trial Information

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2019
• Primary Completion (Estimated): May 12, 2028
• Study Completion (Estimated): May 12, 2028

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (Actual): August 21, 2019

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: MDS; Luspatercept; ACE-536; Beta-thalassemia; Myeloproliferative neoplasm (MPN)-associated myelofibrosis
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Myeloproliferative Disorders; beta-Thalassemia; Hematinics; luspatercept
• Other Study ID Numbers: ACE-536-LTFU-001; U1111-1235-8123 (Registry Identifier: WHO); 2022-502498-40 (Other Identifier: EU CTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No