Phase I Pilot Study of Total-Body Irradiation, Anti-Thymocyte Globulin and Cyclophosphamide Followed By Syngeneic or Autologous Peripheral Blood Stem Cell Transplantation in Patients With Multiple Sclerosis

Study Overview
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Brief Summary
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OBJECTIVES: I. Determine the toxicity of total-body irradiation, anti-thymocyte globulin, and cyclophosphamide followed by syngeneic or autologous peripheral blood stem cell (PBSC) transplantation in patients with multiple sclerosis. II. Determine the disease response of patients treated with this regimen. III. Determine the safety and efficacy of filgrastim (G-CSF) for PBSC mobilization in this patient population.

Detailed Description
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PROTOCOL OUTLINE: This is a multicenter study. Patients receive oral prednisone on days 0-10. Beginning on day 1, patients undergoing autologous peripheral blood stem cell (PBSC) transplantation receive filgrastim (G-CSF) subcutaneously daily until leukapheresis is completed. Leukapheresis begins on approximately day 4 and continues until adequate CD34+ PBSC are collected. PBSC are collected from syngeneic donors in a similar manner. Patients undergo total-body irradiation twice daily on days -5 and -4. Patients receive cyclophosphamide IV on days -3 and -2 and anti-thymocyte globulin IV on days -5, -3, -1, 1, 3, and 5. Patients undergo autologous or syngeneic PBSC transplantation on day 0. Following PBSC transplantation, patients receive oral prednisone on days 7-30 and G-CSF IV daily beginning on day 0 and continuing until blood counts recover. Patients are followed at 30, 80, and 90 days, monthly for 6 months, and then at 1 and 2 years.

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: anti-thymocyte globulin
* Drug: cyclophosphamide
* Drug: filgrastim
* Drug: prednisone
* Procedure: peripheral blood stem cell transplantation
* Procedure: irradiation


Participation Criteria
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Eligibility Criteria
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PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Diagnosis of rapidly progressive multiple sclerosis (MS) by Proser criteria and at high risk for a fatal outcome or severe disability with one of the following: Primary progressive disease Relapsing/remitting disease with 2 or more attacks in 2 years Secondary progressive disease Extended disability status scale (EDSS) between 5.0 and 8.0 with deterioration in the EDSS of 1 or more points over the past year More than 60 days since relapse of MS No evidence of myelodysplasia Sibling donor proven to be an identical twin by ABO typing, HLA typing, and VNTR analysis (for syngeneic transplantation) --Prior/Concurrent Therapy-- Radiotherapy: No prior total-lymphoid irradiation Other: No other concurrent investigational agents --Patient Characteristics-- Hepatic: No hepatic impairment that would preclude high-dose immunosuppressive therapy Renal: No renal impairment that would preclude high-dose immunosuppressive therapy Cardiovascular: No cardiac impairment that would preclude high-dose immunosuppressive therapy Pulmonary: No pulmonary impairment that would preclude high-dose immunosuppressive therapy Other: No neurologic impairment that would preclude high-dose immunosuppressive therapy No active uncontrolled infection No active malignancy No other illness that would severely limit life expectancy No medical or psychiatric conditions that would preclude study No history of hypersensitivity to murine proteins or E. coli-derived proteins No demonstrated lack of compliance with prior medical care Able to undergo an MRI scan HIV negative Not pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: anti-thymocyte globulin|nan|
|Drug: cyclophosphamide|nan|
|Drug: filgrastim|nan|
|Drug: prednisone|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Procedure: irradiation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple sclerosis, neurologic and psychiatric disorders, rare disease