We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04064060
Recruitment Status : Recruiting
First Posted : August 21, 2019
Last Update Posted : March 16, 2023
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE August 9, 2019
First Posted Date  ICMJE August 21, 2019
Last Update Posted Date March 16, 2023
Actual Study Start Date  ICMJE August 12, 2019
Estimated Primary Completion Date March 25, 2030   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 26, 2022)
  • 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
  • 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).
  • 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)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: August 19, 2019)
  • 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
  • Number of subjects 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).
  • Percentage of subjects 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)
  • Number of subjects developing other malignancies/pre-malignancies [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    Development of other malignancies/pre-malignancies
  • Percentage of subjects developing other malignancies/pre-malignancies [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    Development of other malignancies/pre-malignancies
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2022)
  • 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
  • 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 19, 2019)
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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Myelodysplastic Syndromes (MDS)
  • Beta-thalassemia
  • Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis
Intervention  ICMJE 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
Other Name: ACE-536
Study Arms  ICMJE 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.
Intervention: Drug: Luspatercept
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 19, 2019)
665
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 25, 2030
Estimated Primary Completion Date March 25, 2030   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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).
  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) and 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. 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:

  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com 855-907-3286 Clinical.Trials@bms.com
Listed Location Countries  ICMJE Australia,   Belgium,   Bulgaria,   Canada,   France,   Germany,   Greece,   Israel,   Italy,   Japan,   Lebanon,   Malaysia,   Netherlands,   Spain,   Sweden,   Taiwan,   Thailand,   Tunisia,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04064060
Other Study ID Numbers  ICMJE ACE-536-LTFU-001
U1111-1235-8123 ( Registry Identifier: WHO )
2018-002915-93 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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
Current Responsible Party Celgene
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Celgene
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Celgene
Verification Date March 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP