Presented at:
22nd Meeting of the Consortium of Multiple Sclerosis Centers
Denver, CO, May 28-31, 2007
A Phase II Study of High-Dose Immunosuppressive Therapy (HDIT) Using Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) + Thymoglobulin, and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT) for the Treatment of Poor Prognosis Multiple Sclerosis: HALT_MS
Nash RA, Openshaw H, Bowen JD, Forman SJ, Stuve O, Hutton G, Popat U, Kraft G
University of Washington, Seattle; City of Hope, Duarte, CA; Evergreen MS Clinic, Seattle, WA; University of Texas Southwwestern, Dallas, TX; Baylor University, Houston, TX
In vivo depletion of lymphoid effector cells using high-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplantation (HCT) may "reset" the immune system and provide sustained remission of multiple sclerosis (MS). The HALT MS protocol is a Phase II, single arm study of HDIT and autologous HCT for poor prognosis MS. We propose to enroll patients with frequent relapses who have failed conventional treatment, but without advanced disease (EDSS 3.0- 5.5). A HDIT regimen consisting of BEAM and Thymoglobulin will be used followed by infusion of autologous lymphocyte-depleted (CD34-selected) hematopoietic stem cells. This regimen was chosen to provide intensive immunosuppression prior to hematopoietic reconstitution from a lymphocyte‑depleted stem cell population. Durability of disease stabilization as determined by both clinical and diagnostic MRI assessments is the primary objective. Secondary objectives evaluate the safety and efficacy of autologous HCT and immune reconstitution. Tertiary objectives assess central nervous system (CNS) response to treatment using investigative magnetic resonance imaging (MRI), including magnetization transfer ratio (MTR) and magnetic resonance spectroscopy (MRS), and neuroimmunologic studies. Thirty subjects will be enrolled over 2 years at three sites. Subjects will be followed for 5 years after HDIT. The study is now open to enrollment.