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A Phase I Clinical Trial of Rituximab for Pediatric Opsoclonus-Myoclonus Syndrome

Phase 1/Phase 2
6 Months
19 Years
Not Enrolling
Opsoclonus-myoclonus Syndrome, Opsoclonus, Myoclonus, Ataxia

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Trial Information

A Phase I Clinical Trial of Rituximab for Pediatric Opsoclonus-Myoclonus Syndrome

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.

Inclusion Criteria:

- written consent from parents

- have symptomatic OMS

- have CSF B-cell expansion (>1% B-cells)

- adequate renal function as indicated by normal BUN [10-25 mg/dL] and creatinine
[0.4-1.2 mg/dL]

- adequate liver function, as indicated by up to 2x normal AST [0-35 U/L] and ALT [0-35

- men and women of reproductive potential must agree to use an acceptable method of
birth control during treatment and for twelve months after completion of treatment

Exclusion Criteria:

- treatment with any investigational agent within 4 weeks of screening or 5 half-lives
of the investigational drug (which ever is longer)

- receipt of a live vaccine within 4 weeks prior to enrollment

- previous treatment with Rituximab

- prior antibody therapy (does not include IVIg) within past 6 months

- history of severe allergic or anaphylactic reactions to humanized or murine
monoclonal antibodies

- history of HIV (patients considered high risk will be screened)

- history of hepatitis B and/or hepatitis C (patients considered high risk will be

- history of recurrent significant infection or history of recurrent bacterial

- known active bacterial, viral fungal mycobacterial, or other infection (including
tuberculosis or atypical mycobacterial disease, but excluding fungal infections of
nail beds) or any major episode of infection requiring hospitalization or treatment
with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks
prior to screening

- pregnancy (a negative serum pregnancy test should be performed for all women of
childbearing potential within 7 days of treatment)

- significant cardiac (symptomatic arrhythmias or symptomatic structural heart disease)
or pulmonary disease (including obstructive pulmonary disease)

- concomitant chemotherapy

- hemoglobin: >13.5 gm/dL or <10.0 gm/dL

- platelets: <100,000/mm or >500,000/mm K/cumm

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the effectiveness & selectivity of rituximab at depleting CSF B-cells in OMS with intrathecal B-cell expansion. This requires CSF & blood lympocyte immunophenotyping prior to the first infusion & intervals for 1 year after the final infusion.

Principal Investigator

Michael R Pranzatelli, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Pediatric Myoclonus Center


United States: Food and Drug Administration

Study ID:

IND #11,771



Start Date:

June 2005

Completion Date:

December 2007

Related Keywords:

  • Opsoclonus-myoclonus Syndrome
  • Opsoclonus
  • Myoclonus
  • Ataxia
  • opsoclonus
  • myoclonus
  • Ataxia
  • Myoclonus
  • Ocular Motility Disorders
  • Opsoclonus-Myoclonus Syndrome



National Pediatric Myoclonus Center, Department of Neurology, SIU School of Medicine, 751 N Rutledge St Springfield, Illinois  62794