Clinical trial NCT01099930: Autologous Stem Cell Transplant for Multiple Sclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: immunoablation
stem cell transplantation
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Multiple Sclerosis Scientific Research Foundation
First posted: 2010-04-08
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 3 year MS activity free survival
timeFrame: 3 year follow-up post transplant
Secondary outcomes:
measure: Transplant related morbidity
timeFrame: 3 year follow-up post transplant
measure: Transplant related mortality
timeFrame: 3 years
measure: Time to MS treatment failure
timeFrame: 3 years
measure: rate of immune reconstitution following treatment
timeFrame: 3 years
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Harold L Atkins, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Hospital Research Institute
name: Mark S Freedman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Atkins HL, Bowman M, Allan D, Anstee G, Arnold DL, Bar-Or A, Bence-Bruckler I, Birch P, Bredeson C, Chen J, Fergusson D, Halpenny M, Hamelin L, Huebsch L, Hutton B, Laneuville P, Lapierre Y, Lee H, Martin L, McDiarmid S, O'Connor P, Ramsay T, Sabloff M, Walker L, Freedman MS. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet. 2016 Aug 6;388(10044):576-85. doi: 10.1016/S0140-6736(16)30169-6. Epub 2016 Jun 9.
citation: Bose G, Atkins HL, Bowman M, Freedman MS. Autologous hematopoietic stem cell transplantation improves fatigue in multiple sclerosis. Mult Scler. 2019 Nov;25(13):1764-1772. doi: 10.1177/1352458518802544. Epub 2018 Sep 25.
citation: Darlington PJ, Stopnicki B, Touil T, Doucet JS, Fawaz L, Roberts ME, Boivin MN, Arbour N, Freedman MS, Atkins HL, Bar-Or A. Natural Killer Cells Regulate Th17 Cells After Autologous Hematopoietic Stem Cell Transplantation for Relapsing Remitting Multiple Sclerosis. Front Immunol. 2018 May 7;9:834. doi: 10.3389/fimmu.2018.00834. eCollection 2018.