Autologous Hematopoietic Stem Cell Transplant in Neuromyelitis Optica

NCT ID: NCT01339455

Last Updated: 2018-05-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2017-03-31

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.

Conditions

Neuromyelitis Optica

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AHSCT

All patients undergo autologous hematopoietic stem cell transplantation in a two stage process.

Group Type: EXPERIMENTAL

AHSCT

Intervention Type: PROCEDURE

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

Interventions

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

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Jodie Burton MD, MSc, FRCPC

Assistant Professor, University of Calgary

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jodie M Burton, MD,MSc,FRCPC

Role: PRINCIPAL_INVESTIGATOR

Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary

Jan Storek, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Medicine, University of Calgary

Locations

Foothills Medical Centre, University of Calgary

Calgary, Alberta, Canada

Countries

Canada

Other Identifiers

CHREB ID# 23282

Identifier Type: -

Identifier Source: org_study_id