Humanized LL2IGG to Treat Systemic Lupus Erythematosus
This study will examine the safety of a new genetically engineered antibody called hLL2 (epratuzumab) in patients with systemic lupus erythematosus (SLE). It will also evaluate whether hLL2 can lessen overall disease activity in SLE or kidney damage in patients with lupus nephritis.
Patients 18 years of age and older with mild to moderately active SLE may be eligible for this study. Candidates will be screened with blood and urine tests, a chest X-ray, electrocardiogram (EKG), tuberculin skin test, and screening tests for certain cancers.
All participants will receive weekly infusions of hLL2 for 4 weeks. The drug is given through a catheter (small plastic tube) placed through a needle in an arm vein. Each infusion takes about 2 hours, after which the patient is observed in the clinic for 1 to 2 hours before being discharged from the clinic.
The first 3 patients in the study will receive the lowest of three different doses used in the study. If this dose is well tolerated, the next 5 patients will receive a higher dose. If the second dose is tolerated, the last 5 patients will be given the highest dose. If any serious problems are encountered at a dose, patients in the next group will receive either the same or lower dose before being advanced to the next level. Patients in the first group will continue taking prednisone at their regular dose. All other patients will have their prednisone tapered gradually, if their condition permits. Patients who have a disease flare may have their prednisone increased for up to 2 weeks, followed by a gradual taper. If the flare is severe or does not respond to the increased prednisone, the patient will be taken off the study and treated to control the disease.
Patients will be evaluated at various intervals for up to 8 weeks after the last dose. Several of the screening tests will be repeated throughout the study. No more than 500 ml of blood-the equivalent of a single blood donation-will be collected during a 2-month period. Participants may also be asked to undergo the following optional procedures before starting treatment, 1 week after the last dose and 8 weeks after the last treatment dose:
- Bone marrow aspiration - to collect cells from the bone marrow. The hip area is anesthetized and a special needle is used to draw bone marrow from the hipbone.
- Tonsil biopsy - The area to be biopsied is numbed with a local anesthetic and small pieces of tissue will be removed with a special type of forceps. (The procedure may be done under general anesthetic.)
- Magnetic resonance imaging (MRI) of the abdomen - The patient lies on a table within a metal cylinder (the MRI scanner) for about 30 to 40 minutes while images are obtained with the use of a strong magnetic field and radio waves.
|Study Design:||Endpoint Classification: Safety Study
Primary Purpose: Treatment
|Official Title:||A Phase I Clinical Trial of Immunotherapy With Humanized LL2 IgG (Epratuzumab) in Patients With Systemic Lupus Erythematosus|
|Study Start Date:||February 2001|
|Estimated Study Completion Date:||January 2003|
This is a pilot study to evaluate the safety and tolerance of hLL2 (epratuzumab), a humanized anti-CD22 monoclonal antibody, in patients with systemic lupus erythematosus (SLE).
B-lymphocytes play a major role in initiating and maintaining the underlying immunopathological mechanisms of SLE. In addition to producing autoantibodies, they also serve as antigen presenting cells and are able to disrupt peripheral T lymphocyte tolerance. Furthermore, B lymphocyte depletion ameliorates disease activity in animal models of SLE. Therefore, targeted depletion of B-lymphocytes may be of therapeutic benefit in human SLE.
hLL2 (epratuzumab) is a humanized monoclonal antibody that binds to CD22, a surface antigen expressed exclusively on B-lymphocytes. Clinical studies in patients with B cell lymphomas have shown that epratuzumab is safe and well tolerated across a wide range of doses. Although the exact mechanism is unknown, indirect evidence suggests that the antibody is depleting target B lymphocytes. Epratuzumab is made available by Immunomedics, Inc., and will be used under an investigator (NIH)-initiated IND.
In this open-label, Phase I study, up to 20 patients with moderately active SLE may be enrolled. Patients will be treated with weekly infusions of hLL2 in one of three different dosing groups [(240 mg/m(2), 360 mg/m(2), 480 mg/m(2)] for 4 weeks, and followed for 8 weeks after the last dose.
The primary objective is to determine the safety and tolerability of hLL2 in patients with SLE. In addition to safety data, clinical and laboratory data will also be collected for preliminary evaluation of the effectiveness of hLL2 in SLE and to assess the effect of hLL2 on B and T lymphocytes in the lymphoid organs and the peripheral blood. If the treatment is safe and there is preliminary evidence of efficacy, this regimen could be used in controlled trials in the future.
|United States, Maryland|
|National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)|
|Bethesda, Maryland, United States, 20892|