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

NCT00259805 | Completed Phase 1

• 2 other identifiers: CPMC-IRB25.102Genentech CFE-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Chronic Focal Encephalitis; Rasmussen's Encephalitis

Keywords

encephalitis; epilepsy; Rasmussens; rituximab; autoimmune

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  12 months

Secondary Outcomes (1)

• 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.

  12 months

Study Arms (1)

IV Infusion

EXPERIMENTAL

Drug: Rituximab

Interventions

Rituximab DRUG

375 mg/m2 given as an IV infusion once weekly for four doses

IV Infusion

Eligibility Criteria

• Age: 5 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of chronic focal encephalitis
• IgG \& IgM levels within normal limits
• Adequate renal function
• Stable anticonvulsant drug regimen

You may not qualify if:

• Evidence of significant ongoing medical condition or progressive neurologic condition (other than CFE)
• Previous treatment with rituximab
• History of significant recurrent infections, or ongoing active infection
• Receipt of a live vaccine within 4 weeks prior to treatment
• History of severe allergic reactions to humanized or murine monoclonal antibodies
• History of drug, alcohol or chemical abuse within 6 months
• Concomitant malignancies or previous malignancy
• Use of steroids or immunoglobulins during the 4 weeks prior to treatment
• Hemoglobin \<8.5 gm/dL, Platelets \< 100,00/mm, AST or ALT \>2.5 ULN
• Positive Hepatitis B or C serology
• History of positive HIV

Sponsors & Collaborators

• California Pacific Medical Center Research Institute: lead
• Genentech, Inc.: collaborator

Study Sites (1)

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Related Publications (8)

• Baranzini SE, Laxer K, Bollen A, Oksenberg JR. Gene expression analysis reveals altered brain transcription of glutamate receptors and inflammatory genes in a patient with chronic focal (Rasmussen's) encephalitis. J Neuroimmunol. 2002 Jul;128(1-2):9-15. doi: 10.1016/s0165-5728(02)00109-1.

  PMID: 12098505 BACKGROUND

• Prayson RA, Frater JL. Rasmussen encephalitis: a clinicopathologic and immunohistochemical study of seven patients. Am J Clin Pathol. 2002 May;117(5):776-82. doi: 10.1309/AD8R-560C-4V11-C5E2.

  PMID: 12090428 BACKGROUND

• Baranzini SE, Laxer K, Saketkhoo R, Elkins MK, Parent JM, Mantegazza R, Oksenberg JR. Analysis of antibody gene rearrangement, usage, and specificity in chronic focal encephalitis. Neurology. 2002 Mar 12;58(5):709-16. doi: 10.1212/wnl.58.5.709.

  PMID: 11889232 BACKGROUND

• Whitney KD, Andrews PI, McNamara JO. Immunoglobulin G and complement immunoreactivity in the cerebral cortex of patients with Rasmussen's encephalitis. Neurology. 1999 Sep 11;53(4):699-708. doi: 10.1212/wnl.53.4.699.

  PMID: 10489029 BACKGROUND

• Prayson RA, Bingaman W, Frater JL, Wyllie E. Histopathologic findings in 37 cases of functional hemispherectomy. Ann Diagn Pathol. 1999 Aug;3(4):205-12. doi: 10.1016/s1092-9134(99)80052-5.

  PMID: 10459046 BACKGROUND

• Li Y, Uccelli A, Laxer KD, Jeong MC, Vinters HV, Tourtellotte WW, Hauser SL, Oksenberg JR. Local-clonal expansion of infiltrating T lymphocytes in chronic encephalitis of Rasmussen. J Immunol. 1997 Feb 1;158(3):1428-37.

  PMID: 9013988 BACKGROUND

• Hart YM, Cortez M, Andermann F, Hwang P, Fish DR, Dulac O, Silver K, Fejerman N, Cross H, Sherwin A, et al. Medical treatment of Rasmussen's syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients. Neurology. 1994 Jun;44(6):1030-6. doi: 10.1212/wnl.44.6.1030.

  PMID: 8208394 BACKGROUND

• Rasmussen T. Further observations on the syndrome of chronic encephalitis and epilepsy. Appl Neurophysiol. 1978;41(1-4):1-12. doi: 10.1159/000102395.

  PMID: 103497 BACKGROUND

MeSH Terms

Conditions

Encephalitis; Epilepsy

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kenneth D Laxer, M.D.

  California Pacific Medical Center

  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: Medical Doctor

Study Record Dates

• First Submitted: November 29, 2005
• First Posted: December 1, 2005
• Study Start: January 1, 2005
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: March 22, 2013

Record last verified: 2008-03

Locations

US (1)