Study Description

Brief summary:

A Phase 3b, open-label, single-arm, rollover study to evaluate the long-term safety of luspatercept, to the following subjects: Subjects 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 in the opinion of the investigator from continuing treatment with luspatercept. Placebo arm subjects from parent protocol (at the time of unblinding or in follow-up) crossing over to luspatercept treatment (provided subjects have met all requirements for entering the rollover study as per the parent protocol). Subjects 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 (unless they meet requirements as per parent protocol to cross-over to luspatercept treatment). The study design is divided into the Transition Phase, Treatment Phase and Follow-up Phase. Subjects 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 (Screening): up to 21 days prior to enrollment Treatment Phase: For subjects 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. For placebo arm subjects from parent protocol (at the time of unblinding or in follow-up) crossing over to luspatercept treatment (provided subjects have met all requirements for entering the rollover study as per the parent protocol) will start at a luspatercept dose of 1.0 mg/kg every 3 weeks (Q3W). This does not apply to subjects that are in long-term follow-up from the parent protocol. Follow-up Phase: 42 Day Safety Follow-up Phase: subjects 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: All subjects who are continuing in the LTPTFU Phase, will continue to be followed for 5 years from Dose 1 of the parent protocol, or 3 years of post-treatment from last dose of the parent protocol, whichever occurs later. Subjects will be followed every 6 months until death, withdrawal of consent, study termination, or until a subject is lost to follow-up. Subjects 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. Subjects 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 subjects will discontinue from the study when all subjects fulfill 5 years from Dose 1 of the parent protocol, or 3 years of post-treatment from last dose of the parent protocol, whichever occurs later. The shift to commercial drug is an alternative way to stop the study.

• Condition or Disease:Myelodysplastic Syndromes (MDS)
  Beta-thalassemia
  Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis
• Intervention/Treatment: Drug: Luspatercept
• Phase: Phase 3

Detailed Description

N/A

Study Design

Arms and interventions

Outcome Measures

• Primary Outcome Measures: 1. 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
• Primary Outcome Measures: 2. 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).
• Primary Outcome Measures: 3. 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)
• Primary Outcome Measures: 4. 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
• Primary Outcome Measures: 5. 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
• Secondary Outcome Measures: 1. 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

Eligibility Criteria

Information from the National Library of Medicine

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• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

More Information

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT04064060 History of Changes
• Other Study ID Numbers: ACE-536-LTFU-001, U1111-1235-8123, 2018-002915-93
• First Posted: August 21, 2019 Key Record Dates
• Last Update Posted: December 1, 2020
• Last Verified: November 2020

• Individual Participant
  Data (IPD) Sharing
  Statement:

• Plan to Share IPD: Yes
• Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
• Supporting Materials: Study Protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF), Clinical Study Report (CSR), Analytic Code
• Time Frame: See Plan Description
• Access Criteria: See Plan Description
• URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Celgene: ACE-536
  Luspatercept
  MDS Beta-thalassemia
  Myeloproliferative neoplasm (MPN)-associated myelofibrosis
• Additional relevant MeSH terms: Preleukemia
  Myelodysplastic Syndromes
  Primary Myelofibrosis
  Thalassemia
  Myeloproliferative Disorders
  beta-Thalassemia
  Neoplasms
  Bone Marrow Diseases Hematologic Diseases
  Precancerous Conditions
  Anemia, Hemolytic, Congenital
  Anemia, Hemolytic
  Anemia
  Hemoglobinopathies
  Genetic Diseases, Inborn