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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

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
cyclophosphamide
filgrastim
prednisone
peripheral blood stem cell transplantation
irradiation
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring multiple sclerosis, neurologic and psychiatric disorders, rare disease

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope National Medical Center
  • University of Colorado Cancer Center
  • Washington University Barnard Cancer Center
  • University of Nebraska Medical Center
  • Duke University Medical Center
  • Fred Hutchinson Cancer Research Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
April 10, 2001
Last Updated
June 23, 2005
Sponsor
Fred Hutchinson Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00014755
Brief Title
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 Type
Interventional

2. Study Status

Record Verification Date
April 2001
Overall Recruitment Status
Completed
Study Start Date
December 1997 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Center

4. Oversight

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
multiple sclerosis, neurologic and psychiatric disorders, rare disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
35 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
anti-thymocyte globulin
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
irradiation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Nash
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of Colorado Cancer Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Washington University Barnard Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-3330
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22056644
Citation
Bowen JD, Kraft GH, Wundes A, Guan Q, Maravilla KR, Gooley TA, McSweeney PA, Pavletic SZ, Openshaw H, Storb R, Wener M, McLaughlin BA, Henstorf GR, Nash RA. Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results. Bone Marrow Transplant. 2012 Jul;47(7):946-51. doi: 10.1038/bmt.2011.208. Epub 2011 Nov 7.
Results Reference
derived

Learn more about this trial

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

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