Effectiveness of Rituximab in Pediatric OMS Patients.
Condition: Opsoclonus-myoclonus Syndrome; Opsoclonus; Myoclonus; Ataxia
MeSH terms: Opsoclonus-Myoclonus Syndrome; Myoclonus; Ocular Motility Disorders; Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to reduce the symptoms of OMS by testing rituximab (Rituxan®),
      to remove B lymphocytes that make antibodies and trigger brain inflammation. Evidence
      suggests that autoimmune brain inflammation causes the symptoms of OMS. This study of blood
      and spinal fluid intends to find out what effect rituximab has on OMS and on the spinal fluid
      B-cells.

      Rituximab targets and destroys B-cells, which make antibodies that can attack the brain and
      cause may OMS. It is infused through a vein over a period of several hours. Rituximab has
      been used widely and studied extensively since its approval in 1997 by the U.S. Food and Drug
      Administration (FDA) for non-Hodgkin's B-cell Lymphoma (NHL). Today, more than 300,000
      patients have received rituximab, and it is part of more than 200 completed, ongoing, or
      planned clinical trials. Rituximab is not FDA-approved for OMS.
    

Detailed description: 
      Opsoclonus-myoclonus syndrome (OMS) is a rare but pervasive, paraneoplastic neurological
      disorder, purported to be autoantibody-mediated. We demonstrated expansion of B-cells in
      cerebrospinal fluid (CSF) despite tumor resection, chemotherapy, or conventional
      immunotherapy. Whether B-cells can be purged from the CSF compartment with benefit to the
      patient is unknown. Targeting of CSF B lymphocytes represents a novel and valuable paradigm
      shift in the therapy of centrally-mediated paraneoplastic disorders. The objective of this
      preliminary study is to determine if rituximab, a monoclonal antibody against CD20+ B-cells,
      reduces or eliminates CSF B-cells in OMS and whether the reduction results in clinical
      improvement. B lymphocyte subsets and relevant T-cell subsets will be immunophenotyped in the
      CSF and peripheral blood of children with OMS by four-color dual-laser flow cytometry.
      Sixteen children with an increased percentage of CSF B-cells will be treated with rituximab
      375 mg/m2 IV once weekly for four consecutive weeks and CSF testing will be repeated at six
      months with more frequent clinical evaluations and blood testing out to 12 months. Clinical
      outcome will be rated blindly from videotapes by an experienced observer using a validated
      12-item motor evaluation scale and quantifiable parameters of sleep, behavior and motor
      function. Immunological outcome variables will include percentages of B-cell subsets and
      quantitative immunoglobulins. Post-treatment results will be compared to pre-treatment values
      statistically. If rituximab proves to be an efficacious and safe method of treating CSF
      B-cell expansion and the neurological syndrome, this study will lead to a phase II trial with
      the eventual aim of gaining FDA approval of rituximab for this indication.
    

Intervention name(s): rituximab
Intervention type(s): Drug
Intervention MeSH terms: Rituximab
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: opsoclonus; myoclonus