Autologous Hematopoietic Stem Cell Transplant in Neuromyelitis Optica

NCT01339455 | Terminated Phase 1

• 1 other identifier: CHREB ID# 23282
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuromyelitis Optica

Keywords

Neuromyelitis Optica; NMO; Devic's Disease; Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• Proportion relapse-free at three years

  The proportion of surviving patients who are relapse-free at three years after transplant

  3 years

Secondary Outcomes (9)

• Proportion relapse-free at five years

  5 years

• Relapse count

  Annually over 5 years

• Disability progression

  Over 5 years

• Retinal nerve fiber layer (RFNL) status

  5 years

• 25 foot timed walk test

  5 years

Study Arms (1)

AHSCT

EXPERIMENTAL

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

Procedure: AHSCT

Interventions

AHSCT 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

AHSCT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

Foothills Medical Centre, University of Calgary

Calgary, Alberta, T2N 2T9, Canada

Location

MeSH Terms

Conditions

Neuromyelitis Optica

Condition Hierarchy (Ancestors)

Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, University of Calgary

Study Record Dates

• First Submitted: April 18, 2011
• First Posted: April 20, 2011
• Study Start: March 1, 2011
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: May 2, 2018

Record last verified: 2018-04

Locations

CA (1)