Anti-CD20 in Systemic Lupus Erythematosus

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.

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.