Autologous Hematopoietic Stem Cell Transplant in Neuromyelitis Optica

Neuromyelitis Optica Clinical Trial

— SCT-NMO  

Official title:

Autologous Hematopoietic Stem Cell Transplant in Patients With Neuromyelitis Optica

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01339455
• Other study ID #: CHREB ID# 23282
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 2011
• Est. completion date: March 2017

Study information

• Verified date: April 2018
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: March 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Neuromyelitis Optica

Intervention

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

Locations

Country	Name	City	State
Canada	Foothills Medical Centre, University of Calgary	Calgary	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Calgary

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion relapse-free at three years	The proportion of surviving patients who are relapse-free at three years after transplant	3 years
Secondary	Proportion relapse-free at five years	The proportion of surviving patients relapse-free at year five	5 years
Secondary	Relapse count	Number of NMO relapse events	Annually over 5 years
Secondary	Disability progression	Time to progression of EDSS by one step	Over 5 years
Secondary	Retinal nerve fiber layer (RFNL) status	Change in RNFL by optical coherence tomography over trial	5 years
Secondary	25 foot timed walk test	Change in 25 ft timed walk test over trial	5 years
Secondary	PASAT	Annual and change from baseline to end of trial in Paced Auditory Serial Addition Test to assess cognitive function.	Annually over 5 years
Secondary	Hospitalization	Number of hospitalizations, days in hospital over trial period	Over 5 years
Secondary	Overall survival	Survival over trial period	Over 5 years
Secondary	Time to next relapse	Time to next relapse after transplant	Over 5 years