Humanized LL2IGG to Treat Systemic Lupus Erythematosus

NCT00011908 | Completed Phase 1

• 2 other identifiers: 01010801-AR-0108
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Systemic Lupus Erythematosus

Keywords

Safety; B-Lymphocyte Depletion; Anti-CD22; Response; Efficacy; Lupus; Immunotherapy

Interventions

hLL2 (Epratuzumab) DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): lead

Study Sites (1)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22.

  PMID: 3334893 BACKGROUND

• Klimo P, Connors JM. Updated clinical experience with MACOP-B. Semin Hematol. 1987 Apr;24(2 Suppl 1):26-34.

  PMID: 2438779 BACKGROUND

• Dana BW, Dahlberg S, Miller TP, Hartsock RJ, Balcerzak S, Coltman CA, Carden JO, Hartley K, Fisher RI. m-BACOD treatment for intermediate- and high-grade malignant lymphomas: a Southwest Oncology Group phase II trial. J Clin Oncol. 1990 Jul;8(7):1155-62. doi: 10.1200/JCO.1990.8.7.1155.

  PMID: 1694233 BACKGROUND

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

epratuzumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 3, 2001
• First Posted: March 5, 2001
• Study Start: February 1, 2001
• Study Completion: January 1, 2003
• Last Updated: March 4, 2008

Record last verified: 2003-01

Locations

US (1)