Clinical Trial: A Pilot Study of the Use of Rituximab in the Treatment of Chronic Focal Encephalitis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pilot Study of the Use of Rituximab in the Treatment of Chronic Focal Encephalitis

Brief Summary: The purpose of this study is to assess the safety, tolerability and effectiveness of rituximab in the treatment of chronic focal encephalitis.

Detailed Summary:

Chronic Focal Encephalitis (Rasmussen's Encephalitis) is a condition characterized by a progressive hemiparesis, cognitive decline (including loss of language skills if the language dominant hemisphere is involved) and epileptic seizures that are typically refractory to medical treatment (Rasmussen). Attempts to control the seizures with anticonvulsants are ineffective and the only effective treatment to date is a hemispherectomy (surgical removal of half of the brain). Children with CFE who undergo cortical resections or hemispherectomies demonstrate an inflammatory histopathology consisting of perivascular lymphocytic cuffing, gliosis, neuronal loss, microglial nodules and later laminar necrosis and spongy degeneration

Rituximab is a genetically engineered, chimeric; murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant pre-B and mature B cells. It was approved by the FDA in 1997 for the treatment of relapsed or refractory low grade or follicular, CD20+, B-cell non-Hodgkin's lymphoma (NHL). Rituximab binds specifically to the CD20 antigen expressed on the surface of both normal and malignant pre-B and mature B cells. In vitro mechanism of action studies have demonstrated that the Fc portion of Rituximab binds human complement and can lead to cell lysis of the targeted cell through complement-dependent cytotoxicity. Additionally, it has been demonstrated that Rituximab has significant activity in assays of antibody dependent cellular cytotoxicity (Reff et al. 1994). More recently, Rituximab has been shown to induce apoptosis in vitro in DHL-4, a human B cell lymphoma line (Maloney et al. 1997). The relative extent to which these individual mechanisms account for the observed depletion of normal and malignant B cells in vivo is unknown.

While CFE represents only a v
Sponsor: California Pacific Medical Center Research Institute

Current Primary Outcome:

  • To assess the safety and tolerability of Rituximab in the treatment of CFE. Adverse and serious adverse events during the study period, reasonably or probably related to Rituximab, will be assessed at each study visit up to 12 months. [ Time Frame: 12 months ]
  • The natural history of CFE is a progressive deterioration in cortical function; therefore, any evidence of stabilization or improvement in measures of motor function, cognition and/or seizure frequency will be evidence of efficacy and will be assessed at [ Time Frame: 12 months ]


Original Primary Outcome:

  • To assess the safety and tolerability of Rituximab in the treatment of CFE. Adverse and serious adverse events during the study period, reasonably or probably related to Rituximab, will be assessed at each study visit up to 12 months.
  • The natural history of CFE is a progressive deterioration in cortical function; therefore, any evidence of stabilization or improvement in measures of motor function, cognition and/or seizure frequency will be evidence of efficacy and will be assessed at


Current Secondary Outcome: The percentage of patients with a 50% reduction in seizure frequency (responder rate) at 6 months post treatment (as compared to the patient's baseline seizure frequency) will be determined. [ Time Frame: 12 months ]

Original Secondary Outcome:

  • The percentage of patients with a 50% reduction in seizure frequency (responder rate) at 6 months post treatment (as compared to the patient's baseline seizure frequency) will be determined.
  • Laboratory measures of safety will be compared at 3, 6, 9 and 12 months post treatment with baseline values.


Information By: California Pacific Medical Center Research Institute

Dates:
Date Received: November 29, 2005
Date Started: January 2005
Date Completion:
Last Updated: March 20, 2013
Last Verified: March 2008