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

Multiple Sclerosis Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00014755
• Other study ID #: 199/15796
• Secondary ID: FHCRC-1164.00
• Status: Completed
• Phase: Phase 1
• First received: April 10, 2001
• Last updated: June 23, 2005
• Start date: December 1997

Study information

• Verified date: April 2001
• Source: Office of Rare Diseases (ORD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• anti-thymocyte globulin

• cyclophosphamide

• filgrastim

• prednisone

Procedure:
• peripheral blood stem cell transplantation

• irradiation

Locations

Country	Name	City	State
United States	University of Colorado Cancer Center	Denver	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Washington University Barnard Cancer Center	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center

Country where clinical trial is conducted

United States,