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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified October 2025 by Celgene
Sponsor
Celgene
Information Provided by (Responsible Party)
Celgene
Clinicaltrials.gov Identifier
NCT04064060
Other Study ID Numbers:
ACE-536-LTFU-001
First Submitted
August 8, 2019
First Posted
August 20, 2019
Last Update Posted
November 11, 2025
Last Verified
October 2025

ClinicalTrials.gov processed this data on November 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Myelodysplastic Syndromes (MDS)Beta-thalassemiaMyeloproliferative Neoplasm(MPN)-Associated Myelofibrosis
Drug: Luspatercept

Study Design

Study TypeInterventional
Actual Enrollment665 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA 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
Study Start DateAugust 11, 2019
Actual Primary Completion Date1yr 11mos from now
Actual Study Completion Date1yr 11mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
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

Outcome Measures

Primary Outcome Measures
  1. Adverse Events (AEs)
    Type, frequency, severity of AEs, relationship of treatment emergent adverse events to luspatercept
  2. 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).
  3. 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)
  4. Number of participants developing other malignancies/pre-malignancies
    Development of other malignancies/pre-malignancies
  5. Percentage of participants developing other malignancies/pre-malignancies
    Development of other malignancies/pre-malignancies
Secondary Outcome Measures
  1. Overall Survival
    Time from date of randomization until death from any cause
  2. Number of participants developing treatment emergent extramedullary hematopoiesis (EMH) masses
  3. Percentage of participants developing treatment emergent EMH masses

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsCelgene
Locations
Childrens Hospital Los Angeles RHU | Los Angeles California, United States, 90027-6062Local Institution - 971 | Oakland California, United States, 94609Local Institution - 978 | Stanford California, United States, 94305Local Institution - 975 | Tampa Florida, United States, 33612Local Institution - 970 | Chicago Illinois, United States, 60611Local Institution - 973 | Boston Massachusetts, United States, 02115Local Institution - 961 | Detroit Michigan, United States, 48201Local Institution - 969 | New York New York, United States, 10065Local Institution - 967 | Cleveland Ohio, United States, 44195Local Institution - 972 | Philadelphia Pennsylvania, United States, 19104Vanderbilt - Ingram Cancer Center | Nashville Tennessee, United States, 37232-5505The University of Texas - MD Anderson Cancer Center | Houston Texas, United States, 77030Local Institution - 100 | South Brisbane Queensland, Australia, 4101Royal Adelaide Hospital | Adelaide South Australia, Australia, 5000Local Institution - 102 | Clayton Victoria, Australia, 3168Royal Prince Alfred Hospital | Camperdown , Australia, 2050Local Institution - 182 | Brasschaat , Belgium, 2930Local Institution - 180 | Bruges , Belgium, 8000Local Institution - 183 | Ghent , Belgium, 9000Local Institution - 184 | Leuven , Belgium, 3000Local Institution - 220 | Boulevard Sofia, Bulgaria, 1797Local Institution - 221 | Plovdiv , Bulgaria, 4002Local Institution - 262 | Toronto Ontario, Canada, M4N 3M5Local Institution - 260 | Toronto Ontario, Canada, M5G 2C4Local Institution - 263 | Toronto Ontario, Canada, M5G 2M9Local Institution - 131 | Beijing Beijing Municipality, China, 100730Local Institution - 135 | Guangzhou Guangdong, China, 510515Local Institution - 132 | Shanghai Shanghai Municipality, China, 200233Local Institution - 134 | Chengdu Sichuan, China, 610041Local Institution - 130 | Tianjin Tianjin Municipality, China, 300020Local Institution - 133 | Hangzhou Zhejiang, China, 310009Local Institution - 305 | Angers , France, 49033Local Institution - 300 | Créteil , France, 94010Local Institution - 310 | La Tronche , France, 38700Local Institution - 306 | Lille , France, 59037Local Institution - 301 | Marseille , France, 13385Local Institution - 302 | Paris , France, 75010Local Institution - 307 | Pessac , France, 33604Local Institution - 304 | Pierre-Bénite , France, 69495Local Institution - 308 | Strasbourg , France, 67091Local Institution - 309 | Toulouse , France, 31059Local Institution - 303 | Tours , France, 37044Local Institution - 341 | Berlin , Germany, 14195Local Institution - 348 | Dresden , Germany, 01307Local Institution - 345 | Düsseldorf , Germany, 40225Local Institution - 346 | Düsseldorf , Germany, 40479Local Institution - 343 | Halle , Germany, 06120Local Institution - 342 | Hamburg , Germany, 22081Local Institution - 344 | Hanover , Germany, 30625Local Institution - 349 | Leipzig , Germany, 04103Local Institution - 340 | Mainz , Germany, 55131Local Institution - 347 | München , Germany, 81675Aghia Sophia' Children's General Hospital of Athens | Athens , Greece, 115 27Laiko General Hospital of Athens - Center of Thalassemia | Athens , Greece, 115 27Local Institution - 384 | Athens , Greece, 11527Local Institution - 383 | Rio Patras , Greece, 26500Local Institution - 381 | Thessaloniki , Greece, 54642Local Institution - 425 | Afula , Israel, 1834111Local Institution - 420 | Haifa , Israel, 3109601Local Institution - 422 | Jerusalem , Israel, 91031Local Institution - 424 | Jerusalem , Israel, 91120Local Institution - 421 | Nahariya , Israel, 22100Local Institution - 423 | Petah Tikva , Israel, 49100Local Institution - 478 | Florence Tuscany, Italy, 50134Local Institution - 471 | Florence Tuscany, Italy, 50139Local Institution - 470 | Allessandria , Italy, 15100Local Institution - 464 | Bologna , Italy, 40138Local Institution - 466 | Brindisi , Italy, 72100Local Institution - 477 | Cagliari , Italy, 09121Local Institution - 462 | Ferrara , Italy, 44124Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite | Genoa , Italy, 16128Local Institution - 473 | Lecce , Italy, 73100Maggiore Polyclinic Hospital, IRCCS Ca' Granda | Milan , Italy, 20122Local Institution - 479 | Modena , Italy, 41124AORN A Cardarelli | Naples , Italy, 80131AOU dell'Universita degli Studi della Campania Luigi Vanvitelli | Naples , Italy, 80131Azienda Ospedaliero Universitaria S. Luigi Gonzaga | Orbassano , Italy, 10043Local Institution - 469 | Pavia , Italy, 27100Local Institution - 468 | Reggio Calabria , Italy, 89124Local Institution - 465 | Roma , Italy, 133Local Institution - 474 | Rozzano , Italy, 20089Local Institution - 472 | Varese , Italy, 21100Local Institution - 463 | Verona , Italy, 37134Local Institution - 610 | Nagoya Aichi-ken, Japan, 460-0001Local Institution - 601 | Kamogawa Chiba, Japan, 296-0041Matsuyama Red Cross Hospital | Matsuyama Ehime, Japan, 790-8524Ogaki Municipal Hospital | Ōgaki Gifu, Japan, 503-8502Japanese Red Cross Society Himeji Hospital | Himeji Hyōgo, Japan, 6708540Local Institution - 605 | Hitachi Ibaraki, Japan, 317-0077Kitasato University Hospital | Sagamihara Kanagawa, Japan, 252-0329Local Institution - 0979 | Sendai Miyagi, Japan, 980-8574Tohoku University Hospital | Sendai Miyagi, Japan, 980-8574Local Institution - 611 | Nagasaki Nagasaki, Japan, 8528511Japanese Red Cross Medical Center | Shibuya City Tokyo, Japan, 150-8935NTT Medical Center Tokyo | Shinagawa City Tokyo, Japan, 141-8625Local Institution - 612 | Chiba , Japan, 260-0852Shonan Kamakura General Hospital | Kamakura , Japan, 247-8533Osaka Metropolitan University Hospital | Osaka , Japan, 545-8586Local Institution - 604 | Osaka , Japan, 589-8511Chronic Care Center | Hazmiyeh , Lebanon, 00961Local Institution - 545 | Johor Bahru Johor, Malaysia, 80100Hospital Sultanah Bahiyah | Alor Star Kedah, Malaysia, 05460University Malaya Medical Centre | Kuala Lumpur Kuala Lumpur, Malaysia, 59100Hospital Raja Permaisuri Bainun | Ipoh Perak, Malaysia, 30990Queen Elizabeth Hospital | Kota Kinabalu Sabah, Malaysia, 88586Hospital Umum Sarawak | Kuching Sarawak, Malaysia, 93586Local Institution - 580 | Amsterdam , Netherlands, 1081 HVLocal Institution - 681 | Barakaldo , Spain, 48903Local Institution - 686 | Barcelona , Spain, 08908Local Institution - 685 | Barcelona , Spain, 8035Local Institution - 687 | Madrid , Spain, 28028Local Institution - 682 | Oviedo , Spain, 33011Local Institution - 684 | Salamanca , Spain, 37007Local Institution - 680 | Seville , Spain, 41013Local Institution - 683 | Valencia , Spain, 46026Local Institution - 720 | Gothenburg , Sweden, 413 45Local Institution - 722 | Lund , Sweden, SE-221 85Local Institution - 721 | Stockholm , Sweden, 141 86Local Institution - 760 | Kaohsiung, San Ming Dist. , Taiwan, 807China Medical University Hospital | Taichung , Taiwan, 40447Local Institution - 761 | Taipei , Taiwan, 100225Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital | Bangkok , Thailand, 10330Siriraj Hospital Mahidol University | Bangkok , Thailand, 10700Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital | Chiang Mai , Thailand, 50200University Hospital Farhat Hached | Sousse , Tunisia, 4031Bone Marrow Transplant Center | Tunis , Tunisia, 1006Aziza Othmana Hospital | Tunis , Tunisia, 1008Military Hospital of Tunis | Tunis , Tunisia, 1008Local Institution - 881 | Adana , Turkey (Türkiye), 01130Local Institution - 885 | Ankara , Turkey (Türkiye), 06590Local Institution - 882 | Istanbul , Turkey (Türkiye), 34093Local Institution - 884 | Istanbul , Turkey (Türkiye), 34098Local Institution - 880 | Izmir , Turkey (Türkiye), 35100Local Institution - 883 | Mersin , Turkey (Türkiye), 33343Local Institution - 925 | Aberdeen , United Kingdom, AB25 2ZNLocal Institution - 921 | Leeds , United Kingdom, LS9 7TFLocal Institution - 923 | London , United Kingdom, E1 1BBWhittington Hospital | London , United Kingdom, N19 5NFUniversity College London Hospitals NHS Foundation Trust - University College Hospital | London , United Kingdom, NW1 2BULocal Institution - 928 | London , United Kingdom, SE1 9RTLocal Institution - 924 | London , United Kingdom, SE5 9RSLocal Institution - 929 | Oxford , United Kingdom, OX3 7LELocal Institution - 926 | Sutton in Ashfield , United Kingdom, NG17 4JL
Investigators
Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb