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Autologous Hematopoietic Stem Cell Transplant in Neuromyelitis Optica (SCT-NMO)

This study is currently recruiting participants.
Verified April 2011 by University of Calgary
Sponsor:
Information provided by:
University of Calgary
ClinicalTrials.gov Identifier:
NCT01339455
First received: April 18, 2011
Last updated: May 2, 2011
Last verified: April 2011
History of Changes
  Purpose

Neuromyelitis Optica (NMO) is a demyelinating and degenerative disorder of the CNS affecting vision and spinal cord function. This disease is rare compared to Multiple Sclerosis (MS), but it is devastating and often leads to accumulating disability with a 5 year-mortality of approximately 30%. Survivors are typically left with severe morbidity secondary to blindness, quadriparesis and respiratory failure. No agent has been found to be highly effective in halting disease activity. Based on recent outcomes of stem cell transplant trials and reports in autoimmune diseases including MS, and based on the mechanisms of NMO, we anticipate that stem cell transplantation may provide lasting disease stability for NMO patients. The hypothesis of the present trial is that autologous hematopoetic stem cell transplantation in patients with NMO will provide lasting benefit in relapse prevention. Specifically, we anticipate a 50% reduction in the proportion of patients experiencing relapse over a three year period. We will be following patients for a total of five years after transplantation.


Condition Intervention Phase
Neuromyelitis Optica (NMO)
 Procedure: AHSCT
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Autologous Hematopoietic Stem Cell Transplant in Patients With Neuromyelitis Optica

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • Proportion relapse-free at three years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    The proportion of surviving patients who are relapse-free at three years after transplant


Secondary Outcome Measures:
  • Proportion relapse-free at five years [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    The proportion of surviving patients relapse-free at year five

  • Relapse count [ Time Frame: Annually over 5 years ] [ Designated as safety issue: No ]
    Number of NMO relapse events

  • Disability progression [ Time Frame: Over 5 years ] [ Designated as safety issue: No ]
    Time to progression of EDSS by one step

  • Retinal nerve fiber layer (RFNL) status [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Change in RNFL by optical coherence tomography over trial

  • 25 foot timed walk test [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Change in 25 ft timed walk test over trial

  • PASAT [ Time Frame: Annually over 5 years ] [ Designated as safety issue: No ]
    Annual and change from baseline to end of trial in Paced Auditory Serial Addition Test to assess cognitive function.

  • Hospitalization [ Time Frame: Over 5 years ] [ Designated as safety issue: Yes ]
    Number of hospitalizations, days in hospital over trial period

  • Overall survival [ Time Frame: Over 5 years ] [ Designated as safety issue: Yes ]
    Survival over trial period

  • Time to next relapse [ Time Frame: Over 5 years ] [ Designated as safety issue: No ]
    Time to next relapse after transplant


Estimated Enrollment: 10
Study Start Date: March 2011
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AHSCT Procedure: AHSCT

AHSCT Procedure:

  1. Mobilization and Harvesting:

    • Cyclophosphamide
    • Rituximab
    • GSCF
    • Dexamethasone
    • Apheresis

  2. Conditioning and Infusion (3-4 weeks after Mobilization and Harvesting):

    • Cyclophosphamide
    • MESNA
    • Rabbit ATG
    • Rituximab
    • Methylprednisolone
    • Stem Cell infusion
    • GSCF

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18-65, inclusive
  • Diagnosis of NMO using Wingerchuk 2006 NMO Criteria
  • EDSS 0-6.5
  • Treatment with a minimum of one NMO therapy in past 12 months
  • One objective and documented relapse in the past 12 months and two relapse events in the past 24 months despite medical therapy
  • ECOG performance status 0-3
  • Platelets ≥100 x 109/L
  • ALT ≤3 x ULN
  • Total bilirubin ≤2.0 x ULN, except in patients with Gilbert syndrome or in patients in whom the bilirubin rise is of non-hepatic origin
  • Serum creatinine <1.5 x ULN or creatinine clearance ≥50 cc/min
  • Patients must reside in Alberta, Canada for the duration of the transplant period of the trial

Exclusion Criteria:

  • Any illness that would jeopardize the ability of the patient to complete study protocol
  • Prior malignancy unless non-melanoma skin cancer, carcinoma in-situ of the cervix (CIN) or breast, or malignancy treated more than 5 years previously with no evidence of recurrent disease since initial treatment
  • Pregnant or lactating females. Women of childbearing potential must have a negative serum or urine β-hCG pregnancy test at screening
  • Inability or unwillingness to pursue effective means of birth control
  • FEV1/FVC < 50% of predicted
  • DLCO < 50% of predicted
  • Resting LVEF < 50 %
  • Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins, or to iron compounds/medications
  • Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams
  • Unable or unwilling to provide written informed consent for participation
  • Active infection except asymptomatic bacteriuria
  • Any use of investigational therapies within 4 weeks prior to initiation of study treatment
  • Patients dependent on prednisone who cannot be successfully tapered to a maximum of 0.5mg/kg/d prior to mobilization therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01339455

Contacts
Contact: Jodie M Burton, MD, MSc, FRCPC 403 210-6614 jodie.burton@albertahealthservices.ca
Contact: Miles Webb, CCRP 403 944-2589 miles.webb@albertahealthservices.ca

Locations
Canada, Alberta
Foothills Medical Centre, University of Calgary Recruiting
Calgary, Alberta, Canada, T2N 2T9
Sponsors and Collaborators
University of Calgary
Investigators
Principal Investigator: Jodie M Burton, MD, MSc, FRCPC Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Principal Investigator: Jan Storek, MD, PhD Department of Medicine, University of Calgary
  More Information

No publications provided

Responsible Party: Dr. Jodie M. Burton, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
ClinicalTrials.gov Identifier: NCT01339455     History of Changes
Other Study ID Numbers: CHREB ID# 23282
Study First Received: April 18, 2011
Last Updated: May 2, 2011
Health Authority: Canada: Health Canada

Keywords provided by University of Calgary:
Neuromyelitis Optica
NMO
Devic's Disease
Stem Cell Transplant

Additional relevant MeSH terms:
Neuromyelitis Optica
Multiple Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Myelitis, Transverse
Optic Neuritis
 Optic Nerve Diseases
Cranial Nerve Diseases
Demyelinating Diseases
Eye Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on May 16, 2013