Autologous Stem Cell Transplant for Multiple Sclerosis

NCT ID: NCT01099930

Last Updated: 2016-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-08-31
• Study Completion Date: 2016-06-30

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Non-randomized control group

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

Group Type: ACTIVE_COMPARATOR

Standard Therapy

Intervention Type: OTHER

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

Stem Cell Transplantation

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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

Interventions

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

Intervention Type: OTHER

Standard Therapy

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

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Multiple Sclerosis Scientific Research Foundation

UNKNOWN

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Harold L Atkins, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Mark S Freedman, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Locations

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 27291994 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30251913 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29867923 (View on PubMed)

Other Identifiers

200037401H

Identifier Type: -

Identifier Source: org_study_id