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.

Condition	Treatment or Intervention	Phase
Lupus Erythematosus, Systemic	Drug: Rituximab	Phase I

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.

Ages Eligible for Study:  18 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

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.

Jan Stansberry, RN, MSN      215-662-4658    stansber@mail.med.upenn.edu

Pennsylvania
      Jan Stansberry, RN, MSN, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting

Study ID Numbers:  DAIT AC002; SACCC #ASL02; UPenn #U1131s; ACE Study #AC002
Record last reviewed:  September 2003
Record first received:  May 10, 2002
ClinicalTrials.gov Identifier:  NCT00036491
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-08