The Commands Trial
Research type
Research Study
Full title
A Phase 3, Open -label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) versus Epoetin alfa for the Treatment of Anemia due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes (MDS) in ESA Naïve Subjects who require Red Blood Cell Transfusions.
IRAS ID
246762
Contact name
Ciro Rinaldi
Contact email
Sponsor organisation
Celgene Corporation
Eudract number
2017-003190-34
Duration of Study in the UK
8 years, 3 months, 2 days
Research summary
This is a Phase 3, open-label, randomized study to compare the effectiveness and safety of luspatercept against the standard treatment for anaemia due to very low, low or intermediate-risk myelodysplastic syndromes (MDS) in patients who need red blood cell (RBC) transfusions. MDS are a group of disorders that generally affect older adults, in which immature blood cells do not develop into healthy blood cells in the bone marrow. This causes RBC transfusion-dependent anaemia, increased risk of infection, and/or haemorrhage, as well as the risk of developing acute myeloid leukemia. RBC transfusion dependence is associated with poor cardiovascular outcomes and increased mortality in patients.
The use of erythropoiesis stimulating agents (ESAs) is standard of care in lower risk MDS patients. Recent studies with Epoetin alfa have demonstrated clinical effectiveness, but this is limited in size. Therefore, a new treatment option that would increase the frequency of response as well as the duration of RBC-transfusion independence would provide an important clinical benefit in this patient population.
Luspatercept is an RBC-maturing agent that has a mechanism of action distinct from ESAs, and may be more beneficial in the treatment of anaemia in lower-risk MDS patients, particularly those that are ESA-naïve and need RBC transfusions. Early clinical results for luspatercept are promising for RBC response, transfusion independence, and duration of response.
Up to 350 patients will be randomized into one of two treatment arms; Luspatercept, or Epoetin alfa. The study will last approximately 8 years, including two years of enrolment, an additional year of treatment and a 5-year follow-up period.
Safety assessments will include haematology and serum chemistry, adverse events collection, physical examination, vital signs, and electrocardiograms. Efficacy assessments will include collection of transfusion data, assessment of haematological parameters and review of bone marrow aspirate and peripheral blood for MDS disease assessment.
REC name
East Midlands - Nottingham 2 Research Ethics Committee
REC reference
18/EM/0303
Date of REC Opinion
2 Jan 2019
REC opinion
Further Information Favourable Opinion