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

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: Terminated
• Conditions: Neuromyelitis Optica
• Intervention / Treatment: Procedure: AHSCT

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: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / 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:CyclophosphamideRituximabGSCFDexamethasoneApheresis; Conditioning and Infusion (3-4 weeks after Mobilization and Harvesting):CyclophosphamideMESNARabbit ATGRituximabMethylprednisoloneStem Cell infusionGSCF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion relapse-free at three years	The proportion of surviving patients who are relapse-free at three years after transplant	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion relapse-free at five years	The proportion of surviving patients relapse-free at year five	5 years
Relapse count	Number of NMO relapse events	Annually over 5 years
Disability progression	Time to progression of EDSS by one step	Over 5 years
Retinal nerve fiber layer (RFNL) status	Change in RNFL by optical coherence tomography over trial	5 years
25 foot timed walk test	Change in 25 ft timed walk test over trial	5 years
PASAT	Annual and change from baseline to end of trial in Paced Auditory Serial Addition Test to assess cognitive function.	Annually over 5 years
Hospitalization	Number of hospitalizations, days in hospital over trial period	Over 5 years
Overall survival	Survival over trial period	Over 5 years
Time to next relapse	Time to next relapse after transplant	Over 5 years

Collaborators and Investigators

• Sponsor: 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 record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: April 18, 2011
• First Submitted That Met QC Criteria: April 19, 2011
• First Posted (Estimate): April 20, 2011

Study Record Updates

• Last Update Posted (Actual): May 2, 2018
• Last Update Submitted That Met QC Criteria: April 30, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Stem Cell Transplant; NMO; Neuromyelitis Optica; Devic's Disease
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Eye Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Myelitis, Transverse; Optic Neuritis; Neuromyelitis Optica
• Other Study ID Numbers: CHREB ID# 23282