Myelodysplastic Syndromes (MDS)Phase 3NCT04064060
A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials
A Phase 3 study testing Luspatercept in people with Myelodysplastic Syndromes (MDS) and Beta-thalassemia, run by Celgene at 143 sites in 22 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes (MDS), Beta-thalassemia, Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis
- What is being tested?
- Luspatercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 665 participants
- Where
- 143 sitesin 22 countries
- Study dates
- 12 Aug 2019to 12 May 2028
- Phase
- Phase 3
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
- 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
Show all 15Show fewer
- 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:
- 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:
- 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.
- 7. Applies to on treatment participants only- Male participants must:
- 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.
Who cannot join
- 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.
Trial locations and contacts
143 sites in 22 countries. Contact the study team or a site near you to ask about taking part.
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com contact
First line of the email MUST contain NCT # and Site #. contact
143 sites in 22 countries
Italy20 sites, 5 recruiting
- Completed
Local Institution - 470
Allessandria, 15100
- Completed
Local Institution - 464
Bologna, 40138
- Completed
Local Institution - 466
Brindisi, 72100
- Completed
Local Institution - 477
Cagliari, 09121
- Completed
Local Institution - 462
Ferrara, 44124
- Completed
Local Institution - 478
Florence, Tuscany, 50134
- Active, not recruiting
Local Institution - 471
Florence, Tuscany, 50139
- Recruiting
Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite
Genoa, 16128
Manuela Balocco, Site 476, +390105634557
- Completed
Local Institution - 473
Lecce, 73100
- Recruiting
Maggiore Polyclinic Hospital, IRCCS Ca' Granda
Milan, 20122
Maria Domenica Cappellini, Site 467, +390250320288
- Completed
Local Institution - 479
Modena, 41124
- Recruiting
AORN A Cardarelli
Naples, 80131
Paolo Ricchi, Site 475, 390817472256
- Recruiting
AOU dell'Universita degli Studi della Campania Luigi Vanvitelli
Naples, 80131
Silverio Perrotta, Site 461, +0390815665421 0 000
- Recruiting
Azienda Ospedaliero Universitaria S. Luigi Gonzaga
Orbassano, 10043
Giovanni Battista Ferrero, Site 460
- Completed
Local Institution - 469
Pavia, 27100
- Completed
Local Institution - 468
Reggio Calabria, 89124
- Completed
Local Institution - 465
Roma, 133
- Withdrawn
Local Institution - 474
Rozzano, 20089
- Completed
Local Institution - 472
Varese, 21100
- Completed
Local Institution - 463
Verona, 37134
Japan16 sites, 5 recruiting
- Completed
Local Institution - 612
Chiba, 260-0852
- Recruiting
Japanese Red Cross Society Himeji Hospital
Himeji, Hyōgo, 6708540
Yasushi Hiramatsu, Site 614
- Completed
Local Institution - 605
Hitachi, Ibaraki, 317-0077
- Recruiting
Shonan Kamakura General Hospital
Kamakura, 247-8533
Shuku sato, Site 613, +81-467-46-1717
- Completed
Local Institution - 601
Kamogawa, Chiba, 296-0041
- Recruiting
Matsuyama Red Cross Hospital
Matsuyama, Ehime, 790-8524
Tomoaki Fujisaki, Site 606, 810899241111
- Withdrawn
Local Institution - 611
Nagasaki, Nagasaki, 8528511
- Completed
Local Institution - 610
Nagoya, Aichi-ken, 460-0001
- Recruiting
Ogaki Municipal Hospital
Ōgaki, Gifu, 503-8502
Hiroshi Kosugi, Site 608, 81584813341
- Completed
Local Institution - 609
Osaka, 545-8586
- Completed
Local Institution - 603
Sagamihara, Kanagawa, 252-0329
- Completed
Local Institution - 604
Sakai, Osaka, 5900197
- Withdrawn
Local Institution - 0979
Sendai, Miyagi, 980-8574
- Completed
Local Institution - 607
Sendai, Miyagi, 980-8574
- Completed
Local Institution - 602
Shibuya City, Tokyo, 150-8935
- Recruiting
NTT Medical Center Tokyo
Shinagawa City, Tokyo, 141-8625
Motoshi Ichikawa, Site 600, 03-3448-6111
United States12 sites
- Completed
Local Institution - 973
Boston, Massachusetts, 02115
- Completed
Local Institution - 970
Chicago, Illinois, 60611
- Completed
Local Institution - 967
Cleveland, Ohio, 44195
- Completed
Local Institution - 961
Detroit, Michigan, 48201
- Withdrawn
The University of Texas - MD Anderson Cancer Center
Houston, Texas, 77030
- Completed
Local Institution - 968
Los Angeles, California, 90027-6062
- Withdrawn
Vanderbilt - Ingram Cancer Center
Nashville, Tennessee, 37232-5505
- Completed
Local Institution - 969
New York, New York, 10065
- Completed
Local Institution - 971
Oakland, California, 94609
- Completed
Local Institution - 972
Philadelphia, Pennsylvania, 19104
- Completed
Local Institution - 978
Stanford, California, 94305
- Completed
Local Institution - 975
Tampa, Florida, 33612
France11 sites
- Completed
Local Institution - 305
Angers, 49033
- Completed
Local Institution - 300
Créteil, 94010
- Completed
Local Institution - 310
La Tronche, 38700
- Completed
Local Institution - 306
Lille, 59037
- Completed
Local Institution - 301
Marseille, 13385
- Completed
Local Institution - 302
Paris, 75010
- Withdrawn
Local Institution - 307
Pessac, 33604
- Completed
Local Institution - 304
Pierre-Bénite, 69495
- Completed
Local Institution - 308
Strasbourg, 67091
- Completed
Local Institution - 309
Toulouse, 31059
- Withdrawn
Local Institution - 303
Tours, 37044
Germany10 sites
- Completed
Local Institution - 341
Berlin, 14195
- Completed
Local Institution - 348
Dresden, 01307
- Completed
Local Institution - 345
Düsseldorf, 40225
- Completed
Local Institution - 346
Düsseldorf, 40479
- Completed
Local Institution - 343
Halle, 06120
- Completed
Local Institution - 342
Hamburg, 22081
- Completed
Local Institution - 344
Hanover, 30625
- Withdrawn
Local Institution - 349
Leipzig, 04103
- Completed
Local Institution - 340
Mainz, 55131
- Completed
Local Institution - 347
München, 81675
United Kingdom9 sites, 2 recruiting
- Completed
Local Institution - 925
Aberdeen, AB25 2ZN
- Withdrawn
Local Institution - 921
Leeds, LS9 7TF
- Completed
Local Institution - 923
London, E1 1BB
- Recruiting
Whittington Hospital
London, N19 5NF
Emma Drasar, Site 920, +4402072723070
- Recruiting
University College London Hospitals NHS Foundation Trust - University College Hospital
London, NW1 2BU
John Porter, Site 922, 8076846044
- Completed
Local Institution - 928
London, SE1 9RT
- Completed
Local Institution - 924
London, SE5 9RS
- Withdrawn
Local Institution - 929
Oxford, OX3 7LE
- Withdrawn
Local Institution - 926
Sutton in Ashfield, NG17 4JL
Spain8 sites
- Completed
Local Institution - 681
Barakaldo, 48903
- Completed
Local Institution - 686
Barcelona, 08908
- Completed
Local Institution - 685
Barcelona, 8035
- Completed
Local Institution - 687
Madrid, 28028
- Completed
Local Institution - 682
Oviedo, 33011
- Completed
Local Institution - 684
Salamanca, 37007
- Completed
Local Institution - 680
Seville, 41013
- Completed
Local Institution - 683
Valencia, 46026
China6 sites
- Withdrawn
Local Institution - 131
Beijing, Beijing Municipality, 100730
- Withdrawn
Local Institution - 134
Chengdu, Sichuan, 610041
- Withdrawn
Local Institution - 135
Guangzhou, Guangdong, 510515
- Withdrawn
Local Institution - 133
Hangzhou, Zhejiang, 310009
- Withdrawn
Local Institution - 132
Shanghai, Shanghai Municipality, 200233
- Withdrawn
Local Institution - 130
Tianjin, Tianjin Municipality, 300020
Israel6 sites
- Completed
Local Institution - 425
Afula, 1834111
- Completed
Local Institution - 420
Haifa, 3109601
- Completed
Local Institution - 422
Jerusalem, 91031
- Completed
Local Institution - 424
Jerusalem, 91120
- Completed
Local Institution - 421
Nahariya, 22100
- Completed
Local Institution - 423
Petah Tikva, 49100
Malaysia6 sites, 4 recruiting
- Recruiting
Hospital Sultanah Bahiyah
Alor Star, Kedah, 05460
Hong Keng Liew, Site 542, 6047406191
- Recruiting
Hospital Raja Permaisuri Bainun
Ipoh, Perak, 30990
Kamini Kirubamoorthy, Site 546, +60193255800
- Completed
Local Institution - 545
Johor Bahru, Johor, 80100
- Recruiting
Queen Elizabeth Hospital
Kota Kinabalu, Sabah, 88586
Lily Wong, Site 543, 6088517507
- Completed
Local Institution - 544
Kuala Lumpur, Kuala Lumpur, 59100
- Recruiting
Hospital Umum Sarawak
Kuching, Sarawak, 93586
Lee Ping Chew, Site 540, +60165518129
Turkey (Türkiye)6 sites
- Completed
Local Institution - 881
Adana, 01130
- Completed
Local Institution - 885
Ankara, 06590
- Completed
Local Institution - 882
Istanbul, 34093
- Completed
Local Institution - 884
Istanbul, 34098
- Completed
Local Institution - 880
Izmir, 35100
- Completed
Local Institution - 883
Mersin, 33343
Greece5 sites, 1 recruiting
- Recruiting
Aghia Sophia' Children's General Hospital of Athens
Athens, 115 27
Antonis Kattamis, Site 382, +302107467772 0(000)
- Completed
Local Institution - 380
Athens, 115 27
- Completed
Local Institution - 384
Athens, 11527
- Completed
Local Institution - 383
Rio Patras, 26500
- Completed
Local Institution - 381
Thessaloniki, 54642
Australia4 sites, 2 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Devendra Hiwase, Site 103, +61882223369
- Recruiting
Royal Prince Alfred Hospital
Camperdown, 2050
Joy Ho, Site 101, +61295158031
- Completed
Local Institution - 102
Clayton, Victoria, 3168
- Completed
Local Institution - 100
South Brisbane, Queensland, 4101
Belgium4 sites
- Completed
Local Institution - 182
Brasschaat, 2930
- Completed
Local Institution - 180
Bruges, 8000
- Completed
Local Institution - 183
Ghent, 9000
- Completed
Local Institution - 184
Leuven, 3000
Tunisia4 sites, 4 recruiting
- Recruiting
University Hospital Farhat Hached
Sousse, 4031
Khelif Abderahim, Site 840, +21673102503
- Recruiting
Bone Marrow Transplant Center
Tunis, 1006
Monia Ouederni, Site 841, +21693184151 0000 00
- Recruiting
Aziza Othmana Hospital
Tunis, 1008
Karima Kacem, Site 842
- Recruiting
Military Hospital of Tunis
Tunis, 1008
Fehmi M'Sadk, Site 843, +21671393490
Canada3 sites
- Completed
Local Institution - 262
Toronto, Ontario, M4N 3M5
- Completed
Local Institution - 260
Toronto, Ontario, M5G 2C4
- Completed
Local Institution - 263
Toronto, Ontario, M5G 2M9
Sweden3 sites
- Completed
Local Institution - 720
Gothenburg, 413 45
- Completed
Local Institution - 722
Lund, SE-221 85
- Completed
Local Institution - 721
Stockholm, 141 86
Taiwan3 sites
- Completed
Local Institution - 760
Kaohsiung, San Ming Dist., 807
- Completed
Local Institution - 762
Taichung, 40447
- Completed
Local Institution - 761
Taipei, 100225
Thailand3 sites, 3 recruiting
- Recruiting
Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital
Bangkok, 10330
Pranee Sutcharitchan, Site 800, +66022564564
- Recruiting
Siriraj Hospital Mahidol University
Bangkok, 10700
Vip Viprakasit, Site 802, 6624122113
- Recruiting
Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital
Chiang Mai, 50200
Adisak Tantiworawit, Site 801, +66815688875
Bulgaria2 sites
- Completed
Local Institution - 220
Boulevard, Sofia, 1797
- Completed
Local Institution - 221
Plovdiv, 4002
Lebanon1 site, 1 recruiting
- Recruiting
Chronic Care Center
Hazmiyeh, 00961
Ali Taher, Site 500, +9613755669 000000.0
About this study
Official title: 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
Read more
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
- Being tested
- Luspatercept
- Keywords
- ACE-536, Luspatercept, MDS, Beta-thalassemia, Myeloproliferative neoplasm (MPN)-associated myelofibrosis
- Medical subject headings
- Myelodysplastic Syndromes, beta-Thalassemia, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LuspaterceptDrug
Also called ACE-536
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Luspatercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events (AEs)
Type, frequency, severity of AEs, relationship of treatment emergent adverse events to luspatercept
Measured: 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).
Measured: 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)
Measured: 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
Measured: 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
Measured: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Secondary outcomes (3)
Overall Survival
Time from date of randomization until death from any cause
Measured: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Number of participants developing treatment emergent extramedullary hematopoiesis (EMH) masses
Measured: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Percentage of participants developing treatment emergent EMH masses
Measured: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2019
- Study start12 Aug 2019
- Primary completion12 May 2028 (estimated)
- Study completion12 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic Syndromes (MDS)Studies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 665 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04064060
- Sponsor's protocol ID
- ACE-536-LTFU-001
- Other IDs
- U1111-1235-8123, 2022-502498-40
- Status last verified
- Jun 2026
- First submitted
- 9 Aug 2019
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- 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
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 Jul;117(1):161-173. doi: 10.1111/ejh.70161. Epub 2026 Mar 19.
PubMed 41857682