Autologous Stem Cell Transplant for Multiple Sclerosis

NCT01099930 | Completed Phase 2 DMC

• 1 other identifier: 200037401H
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Keywords

immunoablation; stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• 3 year MS activity free survival

  3 year follow-up post transplant

Secondary Outcomes (4)

• 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

Study Arms (2)

Non-randomized control group

ACTIVE COMPARATOR

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

Stem Cell Transplantation

EXPERIMENTAL

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

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

Interventions

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

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

Stem Cell Transplantation

Standard Therapy OTHER

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

Non-randomized control group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Multiple Sclerosis Scientific Research Foundation: collaborator

Study Sites (1)

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Related Publications (3)

• 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.

  PMID: 27291994 BACKGROUND

• 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.

  PMID: 30251913 DERIVED

• 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.

  PMID: 29867923 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Harold L Atkins, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Mark S Freedman, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2010
• First Posted: April 8, 2010
• Study Start: August 1, 2001
• Primary Completion: November 1, 2012
• Study Completion: June 1, 2016
• Last Updated: September 28, 2016

Record last verified: 2016-09

Locations

CA (1)