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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
665
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
Childrens Hospital Los Angeles RHU
Los Angeles, California, United States
RECRUITINGLocal Institution - 971
Oakland, California, United States
COMPLETEDLocal Institution - 978
Stanford, California, United States
COMPLETEDLocal Institution - 975
Tampa, Florida, United States
Adverse Events (AEs)
Type, frequency, severity of AEs, relationship of treatment emergent adverse events to luspatercept
Time frame: From enrollment until at least 42 Day Safety Follow-up Phase
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).
Time frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
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)
Time frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Number of participants developing other malignancies/pre-malignancies
Development of other malignancies/pre-malignancies
Time frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Percentage of participants developing other malignancies/pre-malignancies
Development of other malignancies/pre-malignancies
Time frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Overall Survival
Time from date of randomization until death from any cause
Time frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Number of participants developing treatment emergent extramedullary hematopoiesis (EMH) masses
Time frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Percentage of participants developing treatment emergent EMH masses
Time frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
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Local Institution - 970
Chicago, Illinois, United States
COMPLETEDLocal Institution - 973
Boston, Massachusetts, United States
COMPLETEDLocal Institution - 961
Detroit, Michigan, United States
COMPLETEDLocal Institution - 969
New York, New York, United States
COMPLETEDLocal Institution - 967
Cleveland, Ohio, United States
ACTIVE_NOT_RECRUITINGLocal Institution - 972
Philadelphia, Pennsylvania, United States
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