Multiple sclerosis (MS) affects 350,000 people in the USA and is a worldwide problem. This immune-mediated disease results in lesions of demyelination and impairment of neurological function. The pathogenesis of MS has not been fully defined, although T cell-mediated immune destruction of myelin is thought to be an important element. Current approved therapy (eg. beta-interferon, glatiramer acetate, mitoxantrone) reduces the frequency of relapses but is not curative and does not prevent loss of neurological function or progression to secondary progressive MS.
High-dose immunosuppressive therapy (HDIT) with autologous stem cell transplantation may be effective for the control of severe autoimmune diseases because a preparative regimen can be used that will profoundly suppress the host immune system and may result in immunomodulation for years following treatment. Studies to date have been conducted in patients with secondary progressive MS at which time considerable loss of neurological function had already occurred (EDSS >5.0). Also in secondary progressive MS, it was less clear what immune-mediated events were contributing to loss of neurological function. Therefore, this clinical trial is being conducted in poor-prognosis patients with relapsing-remitting MS who have less advanced (EDSS 3.0-5.5) but active disease and have failed other MS therapies.
The study hypothesis is that intensive immunosuppressive therapy supported by autologous hematopoietic cell infusion will arrest disease activity in patients with poor-prognosis relapsing-remitting MS, as measured by clinical indicators and imaging studies. The primary objective is to determine the 5-year durability of disease stabilization in MS patients after HDIT and autologous HCT. The secondary objectives of the study are to evaluate the safety and efficacy of autologous HCT, immune reconstitution, and mechanisms of disease following autologous HCT for MS through a number of specific endpoints. The tertiary objectives of the study are to evaluate myelin content and axonal integrity using magnetic resonance imaging (MRI) approaches in MS patients undergoing autologous HCT. This study is a prospective, multicenter Phase II clinical trial evaluating high-dose immunosuppressive therapy (HDIT) using Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) plus Thymoglobulin (rATG) with autologous transplantation of CD34+ HCT for the treatment of poor risk multiple sclerosis.