Back to resultsAutologous Hematopoietic Stem Cell Transplant in Neuromyelitis Optica (SCT-NMO)
Primary Purpose
Neuromyelitis Optica
Status
Terminated
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
AHSCT
Sponsored by
About this trial
This is an interventional treatment trial for Neuromyelitis Optica focused on measuring Neuromyelitis Optica, NMO, Devic's Disease, Stem Cell Transplant
Eligibility 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
Sites / Locations
- Foothills Medical Centre, University of Calgary
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AHSCT
Arm Description
All patients undergo autologous hematopoietic stem cell transplantation in a two stage process.
Outcomes
Primary Outcome Measures
Proportion relapse-free at three years
The proportion of surviving patients who are relapse-free at three years after transplant
Secondary Outcome Measures
Proportion relapse-free at five years
The proportion of surviving patients relapse-free at year five
Relapse count
Number of NMO relapse events
Disability progression
Time to progression of EDSS by one step
Retinal nerve fiber layer (RFNL) status
Change in RNFL by optical coherence tomography over trial
25 foot timed walk test
Change in 25 ft timed walk test over trial
PASAT
Annual and change from baseline to end of trial in Paced Auditory Serial Addition Test to assess cognitive function.
Hospitalization
Number of hospitalizations, days in hospital over trial period
Overall survival
Survival over trial period
Time to next relapse
Time to next relapse after transplant
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01339455
Brief Title
Autologous Hematopoietic Stem Cell Transplant in Neuromyelitis Optica
Acronym
SCT-NMO
Official Title
Autologous Hematopoietic Stem Cell Transplant in Patients With Neuromyelitis Optica
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Terminated
Why Stopped
recruitment failure
Study Start Date
March 2011 (undefined)
Primary Completion Date
March 2017 (Actual)
Study Completion Date
March 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Calgary
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuromyelitis Optica
Keywords
Neuromyelitis Optica, NMO, Devic's Disease, Stem Cell Transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AHSCT
Arm Type
Experimental
Arm Description
All patients undergo autologous hematopoietic stem cell transplantation in a two stage process.
Intervention Type
Procedure
Intervention Name(s)
AHSCT
Intervention Description
AHSCT Procedure:
Mobilization and Harvesting:
Cyclophosphamide
Rituximab
GSCF
Dexamethasone
Apheresis
Conditioning and Infusion (3-4 weeks after Mobilization and Harvesting):
Cyclophosphamide
MESNA
Rabbit ATG
Rituximab
Methylprednisolone
Stem Cell infusion
GSCF
Primary Outcome Measure Information:
Title
Proportion relapse-free at three years
Description
The proportion of surviving patients who are relapse-free at three years after transplant
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Proportion relapse-free at five years
Description
The proportion of surviving patients relapse-free at year five
Time Frame
5 years
Title
Relapse count
Description
Number of NMO relapse events
Time Frame
Annually over 5 years
Title
Disability progression
Description
Time to progression of EDSS by one step
Time Frame
Over 5 years
Title
Retinal nerve fiber layer (RFNL) status
Description
Change in RNFL by optical coherence tomography over trial
Time Frame
5 years
Title
25 foot timed walk test
Description
Change in 25 ft timed walk test over trial
Time Frame
5 years
Title
PASAT
Description
Annual and change from baseline to end of trial in Paced Auditory Serial Addition Test to assess cognitive function.
Time Frame
Annually over 5 years
Title
Hospitalization
Description
Number of hospitalizations, days in hospital over trial period
Time Frame
Over 5 years
Title
Overall survival
Description
Survival over trial period
Time Frame
Over 5 years
Title
Time to next relapse
Description
Time to next relapse after transplant
Time Frame
Over 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jodie M Burton, MD,MSc,FRCPC
Organizational Affiliation
Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jan Storek, MD,PhD
Organizational Affiliation
Department of Medicine, University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
Foothills Medical Centre, University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 2T9
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Autologous Hematopoietic Stem Cell Transplant in Neuromyelitis Optica
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