Anti-CD20 in Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and effectiveness of rituximab (anti-CD20) in treating systemic lupus erythematosus (SLE). White blood cells in the body called B cells give off substances that are active in promoting SLE disease. Researchers have found that anti-CD20 can block production of these substances in another disease. This study explores whether anti-CD20 will also be safe in people with SLE and whether it may be effective in treating SLE.

Detailed Description
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B cells clearly play an essential role in the pathogenesis of SLE since they produce autoantibodies. Clinical observations support the contention that intervening in the production of autoantibodies by the B lymphocyte will be effective therapy. Current approved therapy for B-cell non-Hodgkin's lymphoma includes anti-CD20. The results of anti-CD20 administration in SLE are anticipated to be similar to those in lymphoma patients. The current proposal explores the mechanisms and applicability of B-cell depletion as a potential treatment for SLE. Participants receive 4 weekly infusions of study medication. Each participant is enrolled in the study for a total of 1 year with protocol visits weekly for the first 3 months, then every other week for the next 2 months, every month for the next 4 months, and every other month for the remaining 5 months of the study (Weeks 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 13, 15, 19, 23, 27, 31, 39, 47, and 55). Responses to exogenous antigens are measured; assessments for clinical response with SLE-disease activity score (SLEDEI) and systemic lupus activity measure (SLAM) score are performed. Participants complete a health questionnaire and a health survey and laboratory parameters are evaluated.

Official Title
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An Open-Label Safety and Efficacy Study of an Anti-CD20 Antibody (Rituximab, Rituxan®) for Anti-B Cell Therapy in the Treatment of Systemic Lupus Erythematosus

Conditions
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Lupus Erythematosus, Systemic

Intervention / Treatment
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* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria People may be eligible for this study if they: Are 18 to 70 years of age Agree to use a reliable method of birth control during treatment and for 6 months after treatment ends Have SLE (by the American College of Rheumatology criteria) Have had SLE for at least 6 months prior to screening Have active SLE disease at the screening visit Have organ disease (lung, stomach, intestinal, blood, kidney, and/or heart) Have failed standard therapy, including at least 1 immunosuppressive agent, or have experienced side effects from an immunosuppressive agent that required discontinuation of treatment Meet blood, liver, and kidney laboratory values set by the protocol Have not taken an immunosuppressive agent for 2 weeks prior to the first treatment Have been on a stable dose of oral corticosteroids, if taking them, for 4 weeks before the first week's visit. Oral corticosteroids may be altered as medically necessary after enrollment. Have at least 1 elevated autoantibody level at screening visit. Exclusion Criteria People will not be eligible for this study if they: Are pregnant or breast-feeding Have heart, lung, nervous system, kidney, liver, stomach, intestinal, or other diseases that may place the patient at risk if participating in the trial Have cranial neuropathy (a condition affecting the head region) Are on blood-thinning agents to prevent blood clotting Have a serious skin disease Have a certain class of heart disease Have had cancer, unless surgically cured basal cell carcinoma or cervical dysplasia Have a long term serious infectious disease such as tuberculosis or a fungal infection that is now active, or active within 2 years of the baseline visit Have had HIV infection or another immunosuppressive state (chemotherapy or radiation therapy) Have received any experimental drug within 30 days of baseline visit Have received any monoclonal antibody or similar medication within 3 months of the baseline visit Received any intravenous, joint, or muscle injection of corticosteroids within 4 weeks of the baseline visit Abuse alcohol or drugs Are unwilling or unable to follow the protocol Have poor veins for receiving injections.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rituximab<br>375 mg/m^2 administered intravenously | Drug: Rituximab<br>* Subjects received four weekly infusions of rituximab at a dose of 375 mg/m^2<br>* Other names: Rituxan®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Autoantibodies |  | Baseline, Week 4, Week 12, Week 24, Week 36 and Week 56 | 
| Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) |  | Baseline, Week 4, Week 7, Week 11, Week 15, Week 19, Week 27, Week 39 and Week 55 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C3 and C4 complement levels |  |  | 
| Systemic Lupus Activity Measure (SLAM) |  | Baseline, Week 4, Week 7, Week 11, Week 15, Week 19, Week 27, Week 39 and Week 55 | 
| Erythrocyte Sedimentation Rate (ESR) |  |  | 
| Prednisone Dose |  | Baseline, Week 4, Week 12, Week 24, Week 36 and Week 56 | 
| Renal Function | Measured by creatinine clearance and total protein. |  | 
| Modified Health Assessment Questionnaire (HAQ) |  |  | 
| Short Form-36 Health Survey (SF-36) |  |  | 
| Physician Global Assessment (VAS) |  |  | 
| Patient Global Assessment (VAS) |  |  | 
| Systemic Lupus Erythematosus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index for SLE |  |  | 
| Adverse Events |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus, SLE, B-Lymphocytes, anti-CD20, rituximab