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NCT04064060
Recruiting
August 21, 2019
September 23, 2022
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.
N/A
| 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 |
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.
Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com 855-907-3286 Clinical.Trials@bms.com
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
Celgene
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb