A Phase I Clinical Trial of Immunotherapy With Humanized LL2 IgG (Epratuzumab) in Patients With Systemic Lupus Erythematosus

Inclusion Criteria

INCLUSION/EXCLUSION CRITERIA

Patients must be at least 18 years of age at entry.

Patients must give written informed consent prior to entry in the protocol.

Patients must fulfill at least 4 criteria for SLE as defined by the American College of
Rheumatology.

Patients with active lupus not requiring immediate immunosuppressive therapy other than
oral prednisone less than or equal to 0.3 mg/kg/day (or its equivalent) are eligible.
Active lupus is defined by any of these three (a-c) sets of criteria:

a. Chronic proliferative glomerulonephritis with partial or no response to at least 6
months of adequate immunosuppressive therapy (with pulse methylprednisolone,
cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil or high dose daily
corticosteriods), and

i. less than 50% increase in creatinine compared from lowest level during treatment

ii. proteinuria less than or equal to 1.5 times the baseline before treatment

iii less than or equal to 2+ cellular casts in the urinary sediment (on a scale of 0-4),

b. Newly diagnosed proliferative glomerulonephritis with

i. a biopsy showing crescents and/or necrosis in less than 25% of the glomeruli and
minimal or no interstitial fibrosis

ii. proteinuria less than or equal to 3.5 gm/day and albumin greater than or equal to 3.0
gm/dL

iii. creatinine less than or equal to 1.5 mg/dL,

c. Patients with moderately active extra-renal lupus defined as a SLEDAI score between
3-10.

Patients who have renal and extrarenal disease will be included in the study if they
fulfill any of the above inclusion criteria. Their SLEDAI score will be determined based
on the extrarenal features of their disease (non-renal SLEDAI).

Patients must have serum dsDNA level greater than 2 times the upper limit of normal or IgG
anticardiolipin antibody levels greater than or equal to 20 GPL.

Patients must have stable doses of prednisone less than or equal to 0.3 mg/kg/day (or its
equivalent) for at least 2 weeks before the first treatment.

Pregnant or lactating women are not eligible.

Women of childbearing potential and fertile men who are not practicing or who are
unwilling to practice birth control during and for a period of three months after the
completion of the study are excluded from the study.

Patients who have had any therapy with human or murine antibodies or any experimental
therapy within 3 months are not eligible.

Patients who have had therapy with cyclophosphamide, pulse methylprednisolone or IVIg
within 4 weeks or azathioprine, mycophenolate mofetil, cyclosporine or methotrexate within
2 weeks of first study treatment are not eligible.

Patients who have an initiation or a change in the dose of an ACE-inhibitor within 2 weeks
of first study treatment are not eligible.

Patients must not have an allergy to murine or human antibodies.

Patients with serum creatinine greater than 2.5 mg/dL are excluded.

Patients with 24 hour proteinuria greater than 5.5 gm/day are excluded.

Patients who have active severe CNS lupus (encephalopathy, cerebrovascular accident,
transverse myelitis, severe depression, psychosis) are not eligible.

Patient who have a history of thrombosis or recurrent 2nd trimester abortions (3 or more)
and elevated levels of anti-cardiolipin antibodies or lupus anticoagulant unless the
patient is on anticoagulation are not eligible.

Patients who have a history of malignancy with the exception of basal cell carcinoma of
the skin are not eligible.

Patients who have a serious active infection are not eligible.

Patients who have active hepatitis B, hepatitis C or HIV infection are not eligible.

Patients who have a CD4+ lymphocyte count less than 200 are not eligible.

Patients with WBC less than 2000 or ANC less than 1500 or Hgb less than 8.0 or platelets
less than 50,000/microliters or transaminases greater than 2 times the upper limit of
normal or alkaline phosphatase greater than 2 times the upper limit of normal are not
eligible.

Patients must not have a significant concurrent medical condition that, in the opinion of
the principal investigator, could affect the patient's ability to tolerate or complete the
study.