Multiple SclerosisPhase 2MS/BMTNCT01099930
Autologous Stem Cell Transplant for Multiple Sclerosis
A Phase 2 study testing immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT), and Standard Therapy in people with Multiple Sclerosis, run by Ottawa Hospital Research Institute at 1 site in Canada.
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). Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT), and Standard Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2001to Jun 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT),, Standard Therapy
- Keywords
- immunoablation, stem cell transplantation
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
Standard TherapyOther
Patient will receive standard therapy as decided upon by their treating neurologist.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Standard Therapy |
| Stem Cell Transplantation | Experimental | Patients will undergo stem cell transplantation for the treatment of Multiple Sclerosis Receives: Other: immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT), |
What is being measured
The primary outcome is the main question the study is designed to answer.
3 year MS activity free survival
Measured: 3 year follow-up post transplant
Secondary outcomes (4)
Transplant related morbidity
Measured: 3 year follow-up post transplant
Transplant related mortality
Measured: 3 years
Time to MS treatment failure
Measured: 3 years
rate of immune reconstitution following treatment
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2010 (estimated)
- Study startAug 2001
- Primary completionNov 2012
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Multiple Sclerosis Scientific Research Foundation
- Responsible party
- Sponsor
- Investigators
- Harold L Atkins, MD, Principal investigator, Ottawa Hospital Research InstituteMark S Freedman, MD, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01099930
- Sponsor's protocol ID
- 200037401H
- Acronym
- MS/BMT
- Status last verified
- Sep 2016
- First submitted
- 1 Mar 2010
- Last updated
- 28 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 27291994Bose 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.
PubMed 30251913Darlington 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.
PubMed 29867923
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01099930
- Acronym / sponsor ID
- MS/BMT / 200037401H
- Conditions
- Multiple Sclerosis
- Keywords
- immunoablation, stem cell transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Multiple Sclerosis Scientific Research Foundation
- Study start
- Aug 2001
- Primary completion
- Nov 2012 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 8 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-randomized control group | Active comparator | Other: Standard TherapyPatients meeting inclusion/exclusion criteria not consenting to treatment will be requested to consent to control group and followed while receiving standard of care. |
| Stem Cell Transplantation | Experimental | Other: immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT),Patients will undergo stem cell transplantation for the treatment of Multiple Sclerosis |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Other | Stem Cell Transplantation |
| Standard TherapyPatient will receive standard therapy as decided upon by their treating neurologist. | Other | Non-randomized control group |
Primary outcome
3 year MS activity free survival
Time frame: 3 year follow-up post transplant
4 secondary outcomes
Transplant related morbidity
Time frame: 3 year follow-up post transplant
Transplant related mortality
Time frame: 3 years
Time to MS treatment failure
Time frame: 3 years
rate of immune reconstitution following treatment
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2016.
- Background: PubMed 27291994Atkins 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.
- Derived from this study: PubMed 30251913Bose 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.
- Derived from this study: PubMed 29867923Darlington 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Harold L Atkins, MD principal investigator
Ottawa Hospital Research Institute
Mark S Freedman, MD principal investigator
Ottawa Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT), and Standard Therapy in people with Multiple Sclerosis, run by Ottawa Hospital Research Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3 year MS activity free survival (time frame: 3 year follow-up post transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01099930, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2016.