Autologous Stem Cell Transplant for Multiple Sclerosis

Multiple Sclerosis Clinical Trial

— MS/BMT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01099930
• Other study ID #: 200037401H
• Status: Completed
• Phase: Phase 2
• First received: March 1, 2010
• Last updated: September 27, 2016
• Start date: August 2001
• Est. completion date: June 2016

Study information

• Verified date: September 2016
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2016
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

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

Locations

Country	Name	City	State
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	Multiple Sclerosis Scientific Research Foundation

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3 year MS activity free survival		3 year follow-up post transplant	No
Secondary	Transplant related morbidity		3 year follow-up post transplant	Yes
Secondary	Transplant related mortality		3 years	Yes
Secondary	Time to MS treatment failure		3 years	No
Secondary	rate of immune reconstitution following treatment		3 years	No