STREAMS: A Phase 2 Clinical Trial Of Autologous Mesenchymal Stem Cells In Active Multiple Sclerosis (S23.005)

OBJECTIVE: To describe the design and progress of STREAMS (Stem Cells in Rapidly Evolving Active Multiple Sclerosis), the first Phase 2 randomized, double-blind trial of autologous mesenchymal stem cells (MSCs) in highly active MS. BACKGROUND: A number of clinical trials are attempting to exploit the potent immunomodulatory, neuroprotective and potentially reparative properties of MSCs but STREAMS is very distinctive in design, recruiting only patients with highly active MS to this double-blind randomized controlled trial. DESIGN/METHODS: 15 patients with highly active MS will be recruited to this randomized double-blind, crossover study in London, which is also part of the international consortium, MESEMS, recruiting 160 patients in total. Activity is characterized clinically by the presence of relapses and/or progression in the preceding 18 months and radiologically by the presence of a gadolinium enhancing lesion (GEL) on MRI brain within 3 months of the bone marrow harvest. The patient receives either MSCs (standardized at 2x10 6 cells/kg) or placebo at Week 0 and vice versa at Week 24, with clinical assessments and MRIs performed in the intervening weeks. The co-primary outcomes are safety and the number of GELs on sequential MRIs between treatment groups. Secondary outcomes include combined MRI activity, number of relapses, disease progression and changes in the Multiple Sclerosis Functional Composite (MSFC) score. Exploratory work includes an extensive fresh ex-vivo analysis of immune cell populations by 12-color flow-cytometry, mantoux tests, and novel in vitro mechanistic work to understand the immunomodulating action of MSCs. RESULTS: Culture duration has varied from 19-36 days. The mean yield of six harvests was 2.35x10 6 cells/kg with only one harvest below target (1.2x10 6 cells/kg). Five participants have been infused to date and another is in culture. No adverse events have been recorded to date. CONCLUSIONS: The initial results support the safety and feasibility of mesenchymal stem cell therapy. Study Supported by: The UK MS Society and UK Stem Cell Foundation Disclosure: Dr. Ali has nothing to disclose. Dr. Marley has nothing to disclose. Dr. Palanicawandar has nothing to disclose. Dr. Dazzi has nothing to disclose. Dr. Nicholas has received personal compensation for activities with Biogen Idec and Novartis as a consultant, and with Merck Serono and Teva Neuroscience. Dr. Muraro has nothing to disclose.