Multiple Sclerosis
Conditions
Keywords
immunoablation, stem cell transplantation
Brief summary
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.
Interventions
OTHERimmuno-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
OTHERStandard Therapy
Patient will receive standard therapy as decided upon by their treating neurologist.
Sponsors
Multiple Sclerosis Scientific Research Foundation
Ottawa Hospital Research Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 3 year MS activity free survival | 3 year follow-up post transplant |
Secondary
| Measure | Time frame |
|---|---|
| Transplant related morbidity | 3 year follow-up post transplant |
| Transplant related mortality | 3 years |
| Time to MS treatment failure | 3 years |
| rate of immune reconstitution following treatment | 3 years |
Countries
Canada
Outcome results
None listed