Autologous Stem Cell Transplant for Multiple Sclerosis - Full Text View

Sponsor:	Ottawa Hospital Research Institute
Collaborator:	Multiple Sclerosis Scientific Research Foundation
Information provided by:	Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:	NCT01099930

Purpose

Multiple sclerosis is an autoimmune disease. We are studying whether high dose chemotherapy and autologous stem cell transplant can replace the autoreactive immune system and if this reduces clinical inflammatory disease in the central nervous system (CNS). A second goal is to examine whether there is long-term stabilization or improvement in disability scores if the inflammatory disease is controlled.

Condition	Intervention	Phase
Multiple Sclerosis	Other: immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT), Other: Standard Therapy	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Targeting Multiple Sclerosis as an Autoimmune Disease With Intensive Immunoablative Therapy and Immunological Reconstitution: A Potential Curative Therapy for Patients With a Predicted Poor Prognosis

Resource links provided by NLM:

MedlinePlus related topics: Autoimmune Diseases Multiple Sclerosis

U.S. FDA Resources

Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:

3 year MS activity free survival [ Time Frame: 3 year follow-up post transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Transplant related morbidity [ Time Frame: 3 year follow-up post transplant ] [ Designated as safety issue: Yes ]
Transplant related mortality [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Time to MS treatment failure [ Time Frame: 3 years ] [ Designated as safety issue: No ]
rate of immune reconstitution following treatment [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	August 2001
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Non-randomized control group Patients meeting inclusion/exclusion criteria not consenting to treatment will be requested to consent to control group and followed while receiving standard of care.	Other: Standard Therapy Patient will receive standard therapy as decided upon by their treating neurologist.
Experimental: Stem Cell Transplantation Patients will undergo stem cell transplantation for the treatment of Multiple Sclerosis	Other: immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT), Stem Cell Mobilization with Cyclophosphamide 4.5 gm/m2 and rhGCSF 10 ug/kg/d x 10 day. Stem Cell Collection with Cobe Spectra Stem Cell Purification with Miltenyi CliniMACS Stem Cell Transplant Conditioning with Busulphan 9.6 mg/kg iv, Cyclophosphamide 200 mg/kg iv, rabbit ATG 5 mg/kg iv followed by CD34 selected autologous hematopoietic stem cell transplant

Arms

Assigned Interventions

Active Comparator: Non-randomized control group

Patients meeting inclusion/exclusion criteria not consenting to treatment will be requested to consent to control group and followed while receiving standard of care.

Other: Standard Therapy

Patient will receive standard therapy as decided upon by their treating neurologist.

Experimental: Stem Cell Transplantation

Patients will undergo stem cell transplantation for the treatment of Multiple Sclerosis

Other: immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT),

Stem Cell Mobilization with Cyclophosphamide 4.5 gm/m2 and rhGCSF 10 ug/kg/d x 10 day.

Stem Cell Collection with Cobe Spectra Stem Cell Purification with Miltenyi CliniMACS Stem Cell Transplant Conditioning with Busulphan 9.6 mg/kg iv, Cyclophosphamide 200 mg/kg iv, rabbit ATG 5 mg/kg iv followed by CD34 selected autologous hematopoietic stem cell transplant

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age between 18 and 50 years
The diagnosis of active multiple sclerosis with relapses or progression and sustained accumulated impairment, made by a neurologist expert in the field
Patient considered at high risk of progression
EDSS Cerebellar Functional score greater than or equal to 3 OR EDSS Pyramidal Functional score greater than or equal to 3
EDSS between greater than or equal to 3 and less than or equal to 6
Evidence of current disease activity
Evidence of progression or continued relapses or worsening MRI after at least one year of therapy with interferon-B1, glatiramer acetate, Mitoxantrone, or other conventional dose immunosuppressive drug therapy
If a patient has previously received a cytotoxic agent (Mitoxantrone, Cyclophosphamide etc.) they must have normal bone marrow morphology and cytogenetics before being considered eligible for this study
MRI brain scan that satisfies the MRI criteria of Paty or Fazekas for the diagnosis of multiple sclerosis
No evidence of hepatic inflammation or fibrosis

Exclusion Criteria:

Patients with primary progressive multiple sclerosis
Patients with cardiac, renal, pulmonary, hepatic or other organ impairment that would limit their ability to receive dose intensive immunosuppressive therapy including high dose chemotherapy and ASCT
Patient with any active or chronic infection
Patients who are seropositive for HIV1, HIV2, Hepatitis B Surface Antigen, and Hepatitis C
Patients with a previous history of a malignancy other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year
Patients whose life expectancy is severely limited by another co-morbid illness
Patients with evidence of myelodysplasia or other non-autoimmune cytopenia
Patients having received a cytotoxic agent within one month of enrolling in this study
Pregnancy or risk of pregnancy. This includes patients that are unwilling to practice active contraception during the time of chemotherapy
Patients with hypersensitivity to rabbit proteins
Patients unable to give written informed consent in accordance with research ethics board guidelines
Patients having previous exposure to natalizumab or alemtuzumab.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01099930

Locations

Canada, Ontario
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada, K1H 8L6

Sponsors and Collaborators

Ottawa Hospital Research Institute

Multiple Sclerosis Scientific Research Foundation

Investigators

Principal Investigator:	Harold L Atkins, MD	Ottawa Hospital Research Institute
Principal Investigator:	Mark S Freedman, MD	Ottawa Hospital Research Institute

More Information

No publications provided

Responsible Party:	Drs. Harold Atkins and Mark Freedman, Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:	NCT01099930 History of Changes
Other Study ID Numbers:	200037401H
Study First Received:	March 1, 2010
Last Updated:	April 6, 2010
Health Authority:	Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:

immunoablation
stem cell transplantation

Additional relevant MeSH terms:

Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases

Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 23, 2012