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NCT00273364

Stem Cell Therapy for Patients With Multiple Sclerosis Failing Alternate Approved Therapy- A Randomized Study

Completed Phase 2 Results posted Last updated 12 August 2020
What this trial tests

Phase 2 trial testing Hematopoietic Stem Cell Therapy in Multiple Sclerosis in 110 participants. Completed in 30 August 2019.

Timeline
16 November 2005
Primary endpoint
5 January 2017
30 August 2019

Quick facts

Lead sponsorNorthwestern University
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment110
Start date16 November 2005
Primary completion5 January 2017
Estimated completion30 August 2019
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Northwestern University

Who can join

Adults 18 to 55, any sex, with Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Expanded Disability Status Scale (EDSS) Improvement Primary · Pre Treatment, 6 and 12 months Post Treatment

The EDSS scale ranges from 0 to 10 in 0.5 increments that represent higher levels of disability. Improvement in EDSS is defined by both a 0.5 or 1.0 points sustained for more than 6 months.

Pre Treatment
GroupValue95% CI
Hematopoietic Stem Cell Transplantation3.4± 1.2
Standard Therapy for MS3.3± 1.0
6 Months Post Treatment
GroupValue95% CI
Hematopoietic Stem Cell Transplantation2.5± 1.4
Standard Therapy for MS3.7± 1.5
12 Months Post Treatment
GroupValue95% CI
Hematopoietic Stem Cell Transplantation2.4± 1.4
Standard Therapy for MS4± 1.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected during transplant and at 1 year post Treatment. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Hematopoietic Stem Cell Transplantation
Serious: 0/52 (0%)
Deaths: 0/52
Standard Therapy for MS
Serious: 0/55 (0%)
Deaths: 0/55
Other adverse events (4 terms — click to expand)

ReactionSystemHematopoietic Stem Cell Tr…Standard Therapy for MS
HypophosphatemiaMetabolism and nutrition disorders
Febrile Neutropenia (culture negative)General disorders
HypokalemiaMetabolism and nutrition disorders
HypergylcemiaMetabolism and nutrition disorders

Data from ClinicalTrials.gov NCT00273364 adverse events section.

Sponsor's own description

Multiple sclerosis (MS) is at onset an immune-mediated demyelinating disease. In most cases, it starts as a relapsing-remitting disease with distinct attacks and no symptoms between flares. Over years or decades, virtually all cases transition into a progressive disease in which insidious and slow neurologic deterioration occurs with or without acute flares. Relapsing-remitting disease is often responsive to immune suppressive or modulating therapies, while immune based therapies are generally ineffective in patients with a progressive clinical course. This clinical course and response to immune suppression, as well as neuropathology and neuroimaging studies, suggest that disease progression is associated with axonal atrophy. Disability correlates better with measures of axonal atrophy than immune mediated demyelination. Therefore, immune based therapies, in order to be effective, need to be started early in the disease course while MS is predominately an immune-mediated and inflammatory disease. While current immune based therapies delay disability, no intervention has been proven to prevent progressive disability. We propose, as a randomized study, autologous unmanipulated PBSCT using a conditioning regimen of cyclophosphamide and rabbit antithymocyte globulin (rATG) versus FDA approved standard of care (i.e. interferon, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, or tecfidera) in patients with inflammatory (relapsing) MS despite treatment with alternate approved therapy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial.
    Burt RK, Balabanov R, Burman J, Sharrack B, et al · · 2019 · cited 208× · PMID 30644983 · DOI 10.1001/jama.2018.18743
  2. Updates and advances in multiple sclerosis neurotherapeutics.
    Amin M, Hersh CM. · · 2023 · cited 89× · PMID 36314777 · DOI 10.2217/nmt-2021-0058
  3. Advances in the Treatment of Multiple Sclerosis.
    Goldschmidt C, McGinley MP. · · 2021 · cited 44× · PMID 33223085 · DOI 10.1016/j.ncl.2020.09.002
  4. The Use of Stem Cells as a Potential Treatment Method for Selected Neurodegenerative Diseases: Review.
    Cecerska-Heryć E, Pękała M, Serwin N, Gliźniewicz M, et al · · 2023 · cited 39× · PMID 37027074 · DOI 10.1007/s10571-023-01344-6
  5. Hematopoietic stem cell transplantation for multiple sclerosis: collaboration of the CIBMTR and EBMT to facilitate international clinical studies.
    Pasquini MC, Griffith LM, Arnold DL, Atkins HL, et al · · 2010 · cited 34× · PMID 20304084 · DOI 10.1016/j.bbmt.2010.03.012
  6. Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases - a guide for the generalist.
    Snowden JA, Sharrack B, Akil M, Kiely DG, et al · · 2018 · cited 31× · PMID 30072560 · DOI 10.7861/clinmedicine.18-4-329
  7. Autologous hematopoietic stem cell transplantation for autoimmune disease--is it now ready for prime time?
    Atkins HL, Muraro PA, van Laar JM, Pavletic SZ. · · 2012 · cited 25× · PMID 22226104 · DOI 10.1016/j.bbmt.2011.11.020
  8. Autologous Haematopoietic Stem Cell Transplantation in Multiple Sclerosis: a Review of Current Literature and Future Directions for Transplant Haematologists and Oncologists.
    Das J, Sharrack B, Snowden JA. · · 2019 · cited 23× · PMID 30828772 · DOI 10.1007/s11899-019-00505-z

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