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

  • Clinicaltrials.gov identifier

    NCT04064060

  • Recruitment Status

    Recruiting

  • First Posted

    August 21, 2019

  • Last update posted

    September 23, 2022

Study Description

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 rollover study will be terminated, and relevant participants will discontinue from the study when all participants fulfill at least 5 years from the first dose of luspatercept in the parent protocol, or 3 years of post-treatment from last dose, whichever occurs later.

  • Condition or Disease:Myelodysplastic Syndromes (MDS)
    Beta-thalassemia
    Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis
  • Intervention/Treatment: Drug: Luspatercept
  • Phase: Phase 3

Detailed Description

N/A

Study Design

  • Study Type: Interventional
  • Estimated Enrollment: 665 participants
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials
  • Actual Study Start Date: August 2019
  • Estimated Primary Completion Date: March 2030
  • Estimated Study Completion Date: March 2030

Arms and interventions

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

Outcome Measures

  • Primary Outcome Measures: 1. Adverse Events (AEs) [ Time Frame: From enrollment until at least 42 Day Safety Follow-up Phase or EOS (Approximately 5 years). ]
    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. [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    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 [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    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 [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    Development of other malignancies/pre-malignancies
  • 5. Percentage of participants developing other malignancies/pre-malignancies [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    Development of other malignancies/pre-malignancies
  • Secondary Outcome Measures: 1. Overall Survival [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    Time from date of randomization until death from any cause
  • 2. Number of participants developing treatment emergent extramedullary hematopoiesis (EMH) masses [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
  • 3. Percentage of participants developing treatment emergent EMH masses [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]

Eligibility Criteria

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

Criteria

Inclusion Criteria: 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 Long-term Post-treatment Follow-up 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) and 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. 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 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. 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 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: 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.

Contacts and Locations

Contacts

Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com 855-907-3286 Clinical.Trials@bms.com

Locations

Israel
Galilee Medical Center
Nahariya

Israel
HaEmek Medical Center
Afula

Israel
Rambam Health Corporation
Haifa

Israel
Local Institution - 422
Jerusalem

Israel
Shaare Zedek Medical Center
Jerusalem

Israel
Hadassah Medical Center
Jerusalem

Israel
Rabin Medical Center
Petah Tikva

United States, California
Childrens Hospital Los Angeles RHU
Los Angeles

United States, California
Childrens Hospital Los Angeles RHU
Los Angeles

United States, California
UCSF Benioff Children's Hospital Oakland
Oakland

United States, California
Local Institution - 978
Stanford

United States, California
Stanford Cancer Center
Stanford

United States, Florida
Local Institution - 975
Tampa

United States, Florida
Moffitt Cancer Center
Tampa

United States, Illinois
Ann & Robert H Lurie Children's Hospital of Chicago
Chicago

United States, Massachusetts
Boston Children's Hospital
Boston

United States, Michigan
Karmanos Cancer Institute
Detroit

United States, Michigan
Local Institution - 961
Detroit

United States, New York
Weill Cornell Medical College
New York

United States, Ohio
Cleveland Clinic
Cleveland

United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia

United States, Pennsylvania
Local Institution - 972
Philadelphia

United States, Tennessee
Vanderbilt - Ingram Cancer Center
Nashville

United States, Texas
The University of Texas - MD Anderson Cancer Center
Houston

Australia, Queensland
Mater Hospital Brisbane
South Brisbane

Australia, South Australia
Royal Adelaide Hospital
Adelaide

Australia, Victoria
Monash Medical Centre
Clayton

Australia
Royal Prince Alfred Hospital
Camperdown

Australia
Prince of Wales Hospital
Randwick

Belgium
Algemeen Ziekenhuis Klina
Brasschaat

Belgium
AZ Sint-Jan AV Brugge
Brugge

Belgium
Local Institution - 180
Brugge

Belgium
Local Institution - 183
Ghent

Belgium
Universitair Ziekenhuis Gent
Ghent

Belgium
UZ Leuven
Leuven

Bulgaria, Sofia
Local Institution - 220
Boulevard

Bulgaria
University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
Plovdiv

Bulgaria
Specialized Hospital for Active Treatment of Haematological Diseases - Sofia
Sofia

Bulgaria
Multiprofile Hospital for Active Treatment Sveta Marina EAD
Varna

Canada, Ontario
Local Institution - 262
Toronto

Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto

Canada, Ontario
University Health Network
Toronto

Canada, Ontario
Princess Margaret Cancer Centre
Toronto

France
CHU d'Angers
Angers

France
Local Institution - 305
Angers

France
Hopital Henri Mondor
Creteil

France
Centre Hospitalier Universitaire de Grenoble Hopital Albert Michallon
La Tronche

France
CHRU de Lille-Hopital Claude Huriez
Lille

France
Local Institution - 306
Lille

France
Hopitaux de La Timone
Marseille Cedex 9

France
Hopital Saint Louis
Paris

France
Local Institution - 302
Paris

France
Hopital Haut Leveque
Pessac Cedex

France
Centre Hospitalier Lyon Sud
Pierre Benite cedex

France
Hopital civil
Strasbourg

France
Institut Universitaire du Cancer de Toulouse - Oncopole
Toulouse Cedex 9

France
Hopital Bretonneau
Tours

Germany
Medizinisches Versorgungszentrum (MVZ) Onkologischer Schwerpunkt am Oskar-Helene-Heim
Berlin

Germany
Local Institution - 348
Dresden

Germany
Universitatsklinikum Carl Gustav Carus an der TU Dresden
Dresden

Germany
Universitaetsklinikum Duesseldorf
Duesseldorf

Germany
Marien Hospital
Dusseldorf

Germany
Universitatsklinikum Halle Saale
Halle

Germany
Local Institution - 342
Hamburg

Germany
OncoResearch Lerchenfeld GmbH
Hamburg

Germany
Medizinische Hochschule Hannover
Hannover

Germany
Universitatsklinikum Leipzig
Leipzig

Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz

Germany
Klinikum rechts der Isar der Technischen Universitaet Muenchen
München

Greece
Aghia Sophia' Children's General Hospital of Athens
Athens

Greece
Laiko General Hospital of Athens - Center of Thalassemia
Athens

Greece
General Hospital Georgios Gennimatas of Athens
Athens

Greece
University General Hospital of Patras
Rio Patras

Greece
General Hospital of Thessaloniki Hippokration
Thessaloniki

Greece
Local Institution - 381
Thessaloniki

Italy
Azienda Ospedaliera Santi Antonio Biagio E Cesare Arrigo
Allessandria

Italy
Local Institution - 470
Allessandria

Italy
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S.Orsola Malpighi
Bologna

Italy
Presidio Ospedaliero Antonio Perrino
Brindisi

Italy
Azienda Sanitaria Locale (ASL) Cagliari - Ospedale Regionale per le Microcitemie
Cagliari

Italy
Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna
Ferrara

Italy
Azienda Ospedaliera Universitaria Careggi
Firenze

Italy
Azienda Ospedaliera Universitaria Careggi
Firenze

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

Italy
Local Institution - 476
Genoa

Italy
Local Institution - 473
Lecce

Italy
Presidio Ospedaliero Vito Fazzi
Lecce

Italy
Maggiore Polyclinic Hospital, IRCCS Ca' Granda
Milano

Italy
Azienda Ospedaliero Universitaria Di Modena Policlinico
Modena

Italy
AORN A Cardarelli
Napoli

Italy
AOU dell'Università degli Studi della Campania Luigi Vanvitelli
Napoli

Italy
Azienda Ospedaliero Universitaria S. Luigi Gonzaga
Orbassano

Italy
IRCCS Policlinico San Matteo
Pavia

Italy
Azienda Ospedaliera Bianchi Melacrino Morelli
Reggio Di Calabria

Italy
Local Institution - 468
Reggio Di Calabria

Italy
Fondazione PTV Policlinico Tor Vergata
Roma

Italy
Istituto Clinico Humanitas
Rozzano

Italy
Ospedale di Circolo di Varese
Varese

Italy
Azienda Ospedaliera Universitaria Integrata Di Verona
Verona

Japan, Kanagawa
Local Institution - 603
Sagamihara

Japan, Miyagi
Local Institution - 0979
Sendai

Japan, Nagasaki
Local Institution - 611
Nagasaki-shi

Japan, Tokyo
Local Institution - 600
Shinagawa City

Lebanon
Chronic Care Center
Hazmieh

Malaysia, Johor
Hospital Sultanah Aminah
Johor Bahru

Malaysia, Kedah
Hospital Sultanah Bahiyah
Alor Setar

Malaysia, Perak
Hospital Raja Permaisuri Bainun
Ipoh

Malaysia, Sabah
Local Institution - 543
Kota Kinabalu

Malaysia, Sabah
Queen Elizabeth Hospital
Kota Kinabalu

Malaysia, Sarawak
Hospital Umum Sarawak
Kuching

Malaysia, Wilayah Persekutuan Kuala Lumpur
Local Institution - 544
Kuala Lumpur

Malaysia, Wilayah Persekutuan Kuala Lumpur
University Malaya Medical Centre
Kuala Lumpur

Netherlands
Vrije Universiteit Medisch Centrum (VUMC)
Amsterdam

Spain
Hospital Universitario Cruces
Barakaldo

Spain
Hospital Universitari Vall d'Hebron
Barcelona

Spain
Instituto Catalan de Oncologia-Hospital Duran i Reynals
Barcelona

Spain
Local Institution - 686
Barcelona

Spain
Hospital General Universitario Gregorio Marañon
Madrid

Spain
Hospital Universitario Central de Asturias
Oviedo

Spain
Universitario de Salamanca - Hospital Clinico
Salamanca

Spain
Hospital Universitario Virgen del Rocio
Seville

Spain
Hospital Universitari i Politecnic La Fe de Valencia
Valencia

Sweden
Sahlgrenska Universitetssjukhuset
Goteborg

Sweden
Local Institution - 722
Lund

Sweden
Skanes Universitetssjukhus Lund
Lund

Sweden
Karolinska Universitetssjukhuset - Huddinge
Stockholm

Taiwan
Kaohsiung Medical University Hospital
Kaohsiung, San Ming Dist.

Taiwan
China Medical University Hospital
Taichung

Taiwan
National Taiwan University Hospital
Taipei, Zhongzheng Dist.

Thailand
Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital
Bangkok

Thailand
Siriraj Hospital Mahidol University
Bangkok

Thailand
Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital
Chiang Mai

Tunisia
University Hospital Farhat Hached
Sousse

Tunisia
Bone Marrow Transplant Center
Tunis

Tunisia
Aziza Othmana Hospital
Tunis

Tunisia
Military Hospital of Tunis
Tunis

Turkey
Acibadem Adana Hospital
Adana

Turkey
Ankara University Medical Faculty Cebeci Hospital
Ankara

Turkey
Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
Istanbul

Turkey
Local Institution - 882
Istanbul

Turkey
Istanbul University Cerrahpasa Medical Faculty Hospital
Istanbul

Turkey
Ege Universitesi Tip Fakultesi Hastanesi
Izmir

Turkey
Mersin University Medical Faculty
Mersin

United Kingdom
Aberdeen Royal Infirmary
Aberdeen

United Kingdom
The Leeds Teaching Hospitals NHS Trust - St James's University Hospital
Leeds

United Kingdom
Barts Health NHS Trust - The Royal London Hospital
London

United Kingdom
Local Institution - 923
London

United Kingdom
Whittington Hospital
London

United Kingdom
University College London Hospitals NHS Foundation Trust - University College Hospital
London

United Kingdom
Kings College Hospital
London

United Kingdom
Oxford University Hospitals NHS Foundation Trust-Churchill Hospital-Cancer and Haematology Centre
Oxford

United Kingdom
Kings Mill Hospital
Sutton in Ashfield

Sponsors and Collaborators

Celgene

Investigators

Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

More Information

  • Responsible Party: Celgene
  • ClinicalTrials.gov Identifier: NCT04064060 History of Changes
  • Other Study ID Numbers: ACE-536-LTFU-001, U1111-1235-8123, 2018-002915-93
  • First Posted: August 21, 2019 Key Record Dates
  • Last Update Posted: September 23, 2022
  • Last Verified: September 2022
  • Individual Participant
    Data (IPD) Sharing
    Statement:

  • Plan to Share IPD: Yes
  • 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/disclosurecommitment.html
  • Supporting Materials: Study Protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)
  • Time Frame: See Plan Description
  • Access Criteria: See Plan Description
  • URL: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Celgene: ACE-536
    Luspatercept
    MDS
    Beta-thalassemia
    Myeloproliferative neoplasm (MPN)-associated myelofibrosis
  • Additional relevant MeSH terms: Preleukemia
    Myelodysplastic Syndromes
    Primary Myelofibrosis
    Thalassemia
    Myeloproliferative Disorders
    beta-Thalassemia
    Neoplasms
    Bone Marrow Diseases
    Hematologic Diseases
    Precancerous Conditions
    Anemia, Hemolytic, Congenital
    Anemia, Hemolytic
    Anemia
    Hemoglobinopathies
    Genetic Diseases, Inborn