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

April 30, 2018 updated by: Jodie Burton MD, MSc, FRCPC, University of Calgary

Autologous Hematopoietic Stem Cell Transplant in Patients With Neuromyelitis Optica

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Patients who are deemed eligible will be enrolled and undergo a two stage transplant process followed by neurological assessments every 6 months for the following 5 years assessing EDSS, visual metrics, MRI, AQP-4 antibodies, MSFC and SF36.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Foothills Medical Centre, University of Calgary

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AHSCT
All patients undergo autologous hematopoietic stem cell transplantation in a two stage process.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion relapse-free at three years
Time Frame: 3 years
The proportion of surviving patients who are relapse-free at three years after transplant
3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion relapse-free at five years
Time Frame: 5 years
The proportion of surviving patients relapse-free at year five
5 years
Relapse count
Time Frame: Annually over 5 years
Number of NMO relapse events
Annually over 5 years
Disability progression
Time Frame: Over 5 years
Time to progression of EDSS by one step
Over 5 years
Retinal nerve fiber layer (RFNL) status
Time Frame: 5 years
Change in RNFL by optical coherence tomography over trial
5 years
25 foot timed walk test
Time Frame: 5 years
Change in 25 ft timed walk test over trial
5 years
PASAT
Time Frame: Annually over 5 years
Annual and change from baseline to end of trial in Paced Auditory Serial Addition Test to assess cognitive function.
Annually over 5 years
Hospitalization
Time Frame: Over 5 years
Number of hospitalizations, days in hospital over trial period
Over 5 years
Overall survival
Time Frame: Over 5 years
Survival over trial period
Over 5 years
Time to next relapse
Time Frame: Over 5 years
Time to next relapse after transplant
Over 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Calgary

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 18, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 20, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 2, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CHREB ID# 23282

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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