SCT-NMO: Autologous Hematopoietic Stem Cell Transplant in Neuromyelitis Optica
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AHSCT All patients undergo autologous hematopoietic stem cell transplantation in a two stage process. |
Procedure: AHSCT
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
|
Outcome Measures
Primary Outcome Measures
- Proportion relapse-free at three years [3 years]
The proportion of surviving patients who are relapse-free at three years after transplant
Secondary Outcome Measures
- Proportion relapse-free at five years [5 years]
The proportion of surviving patients relapse-free at year five
- Relapse count [Annually over 5 years]
Number of NMO relapse events
- Disability progression [Over 5 years]
Time to progression of EDSS by one step
- Retinal nerve fiber layer (RFNL) status [5 years]
Change in RNFL by optical coherence tomography over trial
- 25 foot timed walk test [5 years]
Change in 25 ft timed walk test over trial
- PASAT [Annually over 5 years]
Annual and change from baseline to end of trial in Paced Auditory Serial Addition Test to assess cognitive function.
- Hospitalization [Over 5 years]
Number of hospitalizations, days in hospital over trial period
- Overall survival [Over 5 years]
Survival over trial period
- Time to next relapse [Over 5 years]
Time to next relapse after transplant
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Foothills Medical Centre, University of Calgary | 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CHREB ID# 23282