A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials
- Conditions
- Myelodysplastic Syndromes (MDS)Beta-thalassemiaMyeloproliferative Neoplasm(MPN)-Associated Myelofibrosis
- Interventions
- Registration Number
- NCT04064060
- Lead Sponsor
- Celgene
- 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 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 665
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 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:
- 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.
- 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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ACE-536 Luspatercept 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.
- Primary Outcome Measures
Name Time Method Percentage of participants developing other malignancies/pre-malignancies Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) Development of other malignancies/pre-malignancies
Adverse Events (AEs) From enrollment until at least 42 Day Safety Follow-up Phase Type, frequency, severity of AEs, relationship of treatment emergent adverse events to luspatercept
Number of participants progressing to high/very high risk MDS or AML. 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).
Percentage of participants progressing to high/very high risk MDS or AML 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)
Number of participants developing other malignancies/pre-malignancies Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) Development of other malignancies/pre-malignancies
- Secondary Outcome Measures
Name Time Method 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) Overall Survival Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) Time from date of randomization until death from any cause
Trial Locations
- Locations (143)
Local Institution - 349
🇩🇪Leipzig, Germany
Local Institution - 340
🇩🇪Mainz, Germany
Local Institution - 424
🇮🇱Jerusalem, Israel
Local Institution - 421
🇮🇱Nahariya, Israel
Local Institution - 423
🇮🇱Petah Tikva, Israel
Local Institution - 477
🇮🇹Cagliari, Italy
Local Institution - 308
🇫🇷Strasbourg, France
Local Institution - 474
🇮🇹Rozzano, Italy
Local Institution - 883
🇹🇷Mersin, Turkey
Local Institution - 462
🇮🇹Ferrara, Italy
Local Institution - 306
🇫🇷Lille, France
Local Institution - 341
🇩🇪Berlin, Germany
Local Institution - 343
🇩🇪Halle, Germany
Local Institution - 342
🇩🇪Hamburg, Germany
Local Institution - 344
🇩🇪Hannover, Germany
Local Institution - 972
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 304
🇫🇷Pierre Benite cedex, France
Local Institution - 468
🇮🇹Reggio Di Calabria, Italy
Childrens Hospital Los Angeles RHU
🇺🇸Los Angeles, California, United States
Local Institution - 971
🇺🇸Oakland, California, United States
Local Institution - 978
🇺🇸Stanford, California, United States
Local Institution - 975
🇺🇸Tampa, Florida, United States
Ann & Robert H Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Local Institution - 961
🇺🇸Detroit, Michigan, United States
Local Institution - 969
🇺🇸New York, New York, United States
Local Institution - 967
🇺🇸Cleveland, Ohio, United States
Vanderbilt - Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
The University of Texas - MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Local Institution - 100
🇦🇺South Brisbane, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Local Institution - 102
🇦🇺Clayton, Victoria, Australia
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
Local Institution - 182
🇧🇪Brasschaat, Belgium
Local Institution - 180
🇧🇪Brugge, Belgium
Local Institution - 183
🇧🇪Ghent, Belgium
Local Institution - 184
🇧🇪Leuven, Belgium
Local Institution - 220
🇧🇬Boulevard, Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
🇧🇬Plovdiv, Bulgaria
Local Institution - 262
🇨🇦Toronto, Ontario, Canada
University Health Network
🇨🇦Toronto, Ontario, Canada
Local Institution - 263
🇨🇦Toronto, Ontario, Canada
Local Institution - 131
🇨🇳Beijing, Beijing, China
Local Institution - 135
🇨🇳Guangzhou, Guangdong, China
Local Institution - 132
🇨🇳Shanghai, Shanghai, China
Local Institution - 134
🇨🇳Chengdu, Sichuan, China
Local Institution - 130
🇨🇳Tianjin, Tianjin, China
Local Institution - 133
🇨🇳Hangzhou, Zhejiang, China
Local Institution - 305
🇫🇷Angers, France
Local Institution - 300
🇫🇷Creteil, France
Local Institution - 310
🇫🇷La Tronche, France
Local Institution - 301
🇫🇷Marseille Cedex 9, France
Local Institution - 302
🇫🇷Paris, France
Local Institution - 307
🇫🇷Pessac Cedex, France
Local Institution - 309
🇫🇷Toulouse Cedex 9, France
Local Institution - 303
🇫🇷Tours, France
Universitatsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪Dresden, Germany
Local Institution - 345
🇩🇪Duesseldorf, Germany
Local Institution - 346
🇩🇪Dusseldorf, Germany
Klinikum Rechts der Isar der Technischen Universitaet Muenchen
🇩🇪München, Germany
Aghia Sophia' Children's General Hospital of Athens
🇬🇷Athens, Greece
Laiko General Hospital of Athens - Center of Thalassemia
🇬🇷Athens, Greece
Local Institution - 384
🇬🇷Athens, Greece
Local Institution - 383
🇬🇷Rio Patras, Greece
General Hospital of Thessaloniki Hippokration
🇬🇷Thessaloniki, Greece
Local Institution - 425
🇮🇱Afula, Israel
Rambam Health Corporation
🇮🇱Haifa, Israel
Local Institution - 422
🇮🇱Jerusalem, Israel
Local Institution - 478
🇮🇹Firenze, Toscana, Italy
Local Institution - 471
🇮🇹Firenze, Toscana, Italy
Local Institution - 470
🇮🇹Allessandria, Italy
Local Institution - 464
🇮🇹Bologna, Italy
Local Institution - 466
🇮🇹Brindisi, Italy
Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite
🇮🇹Genoa, Italy
Local Institution - 473
🇮🇹Lecce, Italy
Maggiore Polyclinic Hospital, IRCCS Ca' Granda
🇮🇹Milano, Italy
Local Institution - 479
🇮🇹Modena, Italy
AORN A Cardarelli
🇮🇹Napoli, Italy
AOU dell'Universita degli Studi della Campania Luigi Vanvitelli
🇮🇹Napoli, Italy
Azienda Ospedaliero Universitaria S. Luigi Gonzaga
🇮🇹Orbassano, Italy
Local Institution - 469
🇮🇹Pavia, Italy
Local Institution - 465
🇮🇹Roma, Italy
Ospedale di Circolo di Varese
🇮🇹Varese, Italy
Local Institution - 463
🇮🇹Verona, Italy
Local Institution - 610
🇯🇵Nagoya, Aichi, Japan
Local Institution - 601
🇯🇵Kamogawa, Chiba, Japan
Matsuyama Red Cross Hospital
🇯🇵Matsuyama, Ehime, Japan
Ogaki Municipal Hospital
🇯🇵Ogaki, Gifu, Japan
Japanese Red Cross Society Himeji Hospital
🇯🇵Himeji, Hyogo, Japan
Local Institution - 605
🇯🇵Hitachi, Ibaraki, Japan
Kitasato University Hospital
🇯🇵Sagamihara, Kanagawa, Japan
Local Institution - 0979
🇯🇵Sendai, Miyagi, Japan
Tohoku University Hospital
🇯🇵Sendai, Miyagi, Japan
Local Institution - 611
🇯🇵Nagasaki-shi, Nagasaki, Japan
Japanese Red Cross Medical Center
🇯🇵Shibuya City, Tokyo, Japan
NTT Medical Center Tokyo
🇯🇵Shinagawa City, Tokyo, Japan
Local Institution - 612
🇯🇵Chiba, Japan
Shonan Kamakura General Hospital
🇯🇵Kamakura, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka, Japan
Local Institution - 604
🇯🇵Osaka, Japan
Chronic Care Center
🇱🇧Hazmieh, Lebanon
Hospital Sultanah Aminah
🇲🇾Johor Bahru, Johor, Malaysia
Hospital Sultanah Bahiyah
🇲🇾Alor Setar, Kedah, Malaysia
Hospital Raja Permaisuri Bainun
🇲🇾Ipoh, Perak, Malaysia
Queen Elizabeth Hospital
🇲🇾Kota Kinabalu, Sabah, Malaysia
Hospital Umum Sarawak
🇲🇾Kuching, Sarawak, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia
Local Institution - 580
🇳🇱Amsterdam, Netherlands
Local Institution - 681
🇪🇸Barakaldo, Spain
Local Institution - 686
🇪🇸Barcelona, Spain
Local Institution - 685
🇪🇸Barcelona, Spain
Local Institution - 687
🇪🇸Madrid, Spain
Local Institution - 682
🇪🇸Oviedo, Spain
Local Institution - 684
🇪🇸Salamanca, Spain
Local Institution - 680
🇪🇸Seville, Spain
Local Institution - 683
🇪🇸Valencia, Spain
Local Institution - 720
🇸🇪Goteborg, Sweden
Local Institution - 722
🇸🇪Lund, Sweden
Local Institution - 721
🇸🇪Stockholm, Sweden
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, San Ming Dist., Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Local Institution - 761
🇨🇳Taipei, Taiwan
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, Thailand
University Hospital Farhat Hached
🇹🇳Sousse, Tunisia
Bone Marrow Transplant Center
🇹🇳Tunis, Tunisia
Aziza Othmana Hospital
🇹🇳Tunis, Tunisia
Military Hospital of Tunis
🇹🇳Tunis, Tunisia
Acibadem Adana Hospital
🇹🇷Adana, Turkey
Local Institution - 885
🇹🇷Ankara, Turkey
Local Institution - 882
🇹🇷Istanbul, Turkey
Local Institution - 884
🇹🇷Istanbul, Turkey
Local Institution - 880
🇹🇷Izmir, Turkey
Local Institution - 925
🇬🇧Aberdeen, United Kingdom
Local Institution - 921
🇬🇧Leeds, 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
Local Institution - 928
🇬🇧London, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Local Institution - 929
🇬🇧Oxford, United Kingdom
Local Institution - 926
🇬🇧Sutton in Ashfield, United Kingdom