Ignite Creation Date:
2024-05-05 @ 12:09 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00259805
Status:
COMPLETED
Last Update Posted:
2013-03-22
First Post:
2005-11-29
Brief Title:
A Pilot Study of the Use of Rituximab in the Treatment of Chronic Focal Encephalitis
Sponsor:
California Pacific Medical Center Research Institute
Organization:
California Pacific Medical Center Research Institute
Study Overview
Official Title:
A Pilot Study of the Use of Rituximab in the Treatment of Chronic Focal Encephalitis
Status:
COMPLETED
Status Verified Date:
2008-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 Description:
Chronic Focal Encephalitis Rasmussens 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 murinehuman 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-Hodgkins 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 very small percentage of patients with epilepsy the devastating progressive nature of the disease with out any adequate treatments relegates these children to the relentless loss of cognitive and motor skills and continuing seizures Recent evidence suggests this condition is immune mediated and includes the development of antibodies directed against various brain components including glutamate receptors GluR3 Rogers Brain samples from patients with CFE have demonstrated immunoreactivity for IgG C4 C8 and MAC Andrews and Whitney and involvement of both B and T-lymphocytes Evidence supporting a role for clonally expanded B lymphocytes was found by Baranzini By analyzing the T-cell receptor expression in brain lesions using PCR these investigators also demonstrated the local immune response in CFE included restricted T-cell populations probably expanding from a few precursor T-cells responding to discrete antigenic epitopes Li Following demonstration of antibodies directed against brain elements in CFE a patient was treated with plasma exchange which produced a significant improvement in seizure frequency cognition and hemiparesis lending support to the hypothesis that circulating antibodies contribute to the disease pathogenesis Subsequently attempts to modify this disease by immune modification plasmaphoresis steroids gamma globulin have demonstrated modest improvements but the improvements have been short-lived and have not affected the natural progression of this disease This pilot study proposes to directly attack the cells B-cells thought to be instrumental in the development of this condition Should this approach to treating CFE be successful it will have a major impact on these childrens lives
Rituximab is a genetically engineered chimeric murinehuman 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-Hodgkins 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 very small percentage of patients with epilepsy the devastating progressive nature of the disease with out any adequate treatments relegates these children to the relentless loss of cognitive and motor skills and continuing seizures Recent evidence suggests this condition is immune mediated and includes the development of antibodies directed against various brain components including glutamate receptors GluR3 Rogers Brain samples from patients with CFE have demonstrated immunoreactivity for IgG C4 C8 and MAC Andrews and Whitney and involvement of both B and T-lymphocytes Evidence supporting a role for clonally expanded B lymphocytes was found by Baranzini By analyzing the T-cell receptor expression in brain lesions using PCR these investigators also demonstrated the local immune response in CFE included restricted T-cell populations probably expanding from a few precursor T-cells responding to discrete antigenic epitopes Li Following demonstration of antibodies directed against brain elements in CFE a patient was treated with plasma exchange which produced a significant improvement in seizure frequency cognition and hemiparesis lending support to the hypothesis that circulating antibodies contribute to the disease pathogenesis Subsequently attempts to modify this disease by immune modification plasmaphoresis steroids gamma globulin have demonstrated modest improvements but the improvements have been short-lived and have not affected the natural progression of this disease This pilot study proposes to directly attack the cells B-cells thought to be instrumental in the development of this condition Should this approach to treating CFE be successful it will have a major impact on these childrens lives
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| Genentech CFE-001 | None | None | None |