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Autologous Stem Cell Transplant for Multiple Sclerosis (MS/BMT)

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT),
Standard Therapy
Sponsored by
Ottawa Hospital Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring immunoablation, stem cell transplantation

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Ottawa Hospital Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Non-randomized control group

Stem Cell Transplantation

Arm Description

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

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

Outcomes

Primary Outcome Measures

3 year MS activity free survival

Secondary Outcome Measures

Transplant related morbidity
Transplant related mortality
Time to MS treatment failure
rate of immune reconstitution following treatment

Full Information

First Posted
March 1, 2010
Last Updated
September 27, 2016
Sponsor
Ottawa Hospital Research Institute
Collaborators
Multiple Sclerosis Scientific Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01099930
Brief Title
Autologous Stem Cell Transplant for Multiple Sclerosis
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
August 2001 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
Collaborators
Multiple Sclerosis Scientific Research Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
immunoablation, stem cell transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Non-randomized control group
Arm Type
Active Comparator
Arm Description
Patients meeting inclusion/exclusion criteria not consenting to treatment will be requested to consent to control group and followed while receiving standard of care.
Arm Title
Stem Cell Transplantation
Arm Type
Experimental
Arm Description
Patients will undergo stem cell transplantation for the treatment of Multiple Sclerosis
Intervention Type
Other
Intervention Name(s)
immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT),
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Standard Therapy
Intervention Description
Patient will receive standard therapy as decided upon by their treating neurologist.
Primary Outcome Measure Information:
Title
3 year MS activity free survival
Time Frame
3 year follow-up post transplant
Secondary Outcome Measure Information:
Title
Transplant related morbidity
Time Frame
3 year follow-up post transplant
Title
Transplant related mortality
Time Frame
3 years
Title
Time to MS treatment failure
Time Frame
3 years
Title
rate of immune reconstitution following treatment
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harold L Atkins, MD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mark S Freedman, MD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
27291994
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.
Results Reference
background
PubMed Identifier
30251913
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.
Results Reference
derived
PubMed Identifier
29867923
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.
Results Reference
derived

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Autologous Stem Cell Transplant for Multiple Sclerosis

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