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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04064060




Registration number
NCT04064060
Ethics application status
Date submitted
9/08/2019
Date registered
21/08/2019
Date last updated
29/10/2024

Titles & IDs
Public title
A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials
Scientific 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
Secondary ID [1] 0 0
U1111-1235-8123
Secondary ID [2] 0 0
ACE-536-LTFU-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes (MDS) 0 0
Beta-thalassemia 0 0
Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Luspatercept

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.


Treatment: Drugs: 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-ß (TGF-ß) superfamily. Members of the TGF-ß 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events (AEs)
Timepoint [1] 0 0
From enrollment until at least 42 Day Safety Follow-up Phase
Primary outcome [2] 0 0
Number of participants progressing to high/very high risk MDS or AML.
Timepoint [2] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Primary outcome [3] 0 0
Percentage of participants progressing to high/very high risk MDS or AML
Timepoint [3] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Primary outcome [4] 0 0
Number of participants developing other malignancies/pre-malignancies
Timepoint [4] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Primary outcome [5] 0 0
Percentage of participants developing other malignancies/pre-malignancies
Timepoint [5] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Secondary outcome [2] 0 0
Number of participants developing treatment emergent extramedullary hematopoiesis (EMH) masses
Timepoint [2] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Secondary outcome [3] 0 0
Percentage of participants developing treatment emergent EMH masses
Timepoint [3] 0 0
Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
12/05/2028
Actual
Sample size
Target
665
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - 100 - South Brisbane
Recruitment hospital [2] 0 0
Local Institution - 103 - Adelaide
Recruitment hospital [3] 0 0
Local Institution - 102 - Clayton
Recruitment hospital [4] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Florida
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Illinois
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Massachusetts
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Michigan
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Ohio
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Pennsylvania
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Tennessee
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Texas
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Belgium
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Brasschaat
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Belgium
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Brugge
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Belgium
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Ghent
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Belgium
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Leuven
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Bulgaria
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Sofia
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Bulgaria
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Plovdiv
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Canada
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Ontario
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China
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Beijing
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China
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Guangdong
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China
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Shanghai
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China
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Tianjin
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China
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Zhejiang
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Angers
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Creteil
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La Tronche
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Lille
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Marseille Cedex 9
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Paris
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Pessac Cedex
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France
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Pierre Benite cedex
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Strasbourg
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France
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Toulouse Cedex 9
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Tours
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Germany
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Berlin
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Dresden
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Duesseldorf
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Halle
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Hamburg
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Hannover
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Germany
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Leipzig
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Mainz
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Germany
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München
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Greece
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Athens
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Greece
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Rio Patras
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Greece
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Thessaloniki
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Israel
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Afula
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Haifa
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Israel
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Jerusalem
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Israel
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Nahariya
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Israel
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Petah Tikva
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Toscana
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Allessandria
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Bologna
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Brindisi
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Ferrara
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Genoa
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Lecce
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Modena
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Napoli
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Pavia
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Reggio Di Calabria
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Roma
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Rozzano
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Varese
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Verona
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Japan
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Aichi
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Chiba
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Ehime
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Gifu
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Hyogo
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Ibaraki
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Tokyo
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Kamakura
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Osaka
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Lebanon
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Hazmieh
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Malaysia
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Johor
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Kedah
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Perak
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Malaysia
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Sabah
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Malaysia
State/province [88] 0 0
Sarawak
Country [89] 0 0
Malaysia
State/province [89] 0 0
Wilayah Persekutuan Kuala Lumpur
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Netherlands
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Amsterdam
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Spain
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Barakaldo
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Oviedo
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Spain
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Salamanca
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Spain
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Seville
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Spain
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Valencia
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Sweden
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Goteborg
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Sweden
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Lund
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Sweden
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Stockholm
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Taiwan
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Kaohsiung, San Ming Dist.
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Taiwan
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Taichung
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Taiwan
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Taipei
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Thailand
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Bangkok
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Thailand
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Chiang Mai
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Tunisia
State/province [106] 0 0
Sousse
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Tunisia
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Tunis
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Turkey
State/province [108] 0 0
Adana
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Turkey
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Ankara
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Mersin
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United Kingdom
State/province [113] 0 0
Aberdeen
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United Kingdom
State/province [114] 0 0
Leeds
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United Kingdom
State/province [115] 0 0
London
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United Kingdom
State/province [116] 0 0
Oxford
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Sutton in Ashfield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04064060
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BMS Study Connect Contact Center www.BMSStudyConnect.com
Address 0 0
Country 0 0
Phone 0 0
855-907-3286
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04064060