rious infusion reactions. Patients should be carefully monitored during infusions and Campath discontinued if indicated. (See DOSAGE AND ADMINISTRATION.) Gradual escalation to the recommended maintenance dose is required at the initiation of therapy and after interruption of therapy for 7 or more days. · Infections, Opportunistic Infections: Serious, sometimes fatal bacterial, viral, fungal, and protozoan infections have been reported in patients receiving Campath therapy. Prophylaxis directed against Pneumocystis carinii pneumonia (PCP) and herpes virus infections has been shown to decrease, but not eliminate, the occurrence of these infections.
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Campath® (ALEMTUZUMAB)
DESCRIPTION
Campath® (Alemtuzumab) is a recombinant DNA-derived humanized monoclonal antibody (Campath-1H) that is directed against the 21-28 kD cell surface glycoprotein, CD52. CD52 is expressed on the surface of normal and malignant B and T lymphocytes, NK cells, monocytes, macrophages, and tissues of the male reproductive system. The Campath-1H antibody is an IgG1 kappa with human variable framework and constant regions, and complementarity-determining regions from a murine (rat) monoclonal antibody (Campath-1G). The Campath-1H antibody has an approximate molecular weight of 150 kD.
Campath is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin. Neomycin is not detectable in the final product. Campath is a sterile, clear, colorless, isotonic pH 6.8-7.4 solution for injection. Each single use ampoule of Campath contains 30 mg Alemtuzumab, 24.0 mg sodium chloride, 3.5 mg dibasic sodium phosphate, 0.6 mg potassium chloride, 0.6 mg monobasic potassium phosphate, 0.3 mg polysorbate 80, and 0.056 mg disodium edetate. No preservatives are added.
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CLINICAL PHARMACOLOGY
General:
Alemtuzumab binds to CD52, a non-modulating antigen that is present on the surface of essentially all B and T lymphocytes, a majority of monocytes, macrophages, and NK cells, and a subpopulation of granulocytes. Analysis of samples collected from multiple volunteers has not identified CD52 expression on erythrocytes or hematopoetic stem cells. The proposed mechanism of action is antibody-dependent lysis of leukemic cells following cell surface binding. Campath-1H Fab binding was observed in lymphoid tissues and the mononuclear phagocyte system. A proportion of bone marrow cells, including some CD34+ cells, express variable levels of CD52. Significant binding was also observed in the skin and male reproductive tract (epididymis, sperm, seminal vesicle). Mature spermatozoa stain for CD52, but neither spermatogenic cells nor immature spermatozoa show evidence of staining.
Human Pharmacokinetics:
The pharmacokinetic profile of Alemtuzumab was studied in a multicenter rising-dose trial in non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Campath was administered once weekly for a maximum of 12 weeks. Following intravenous infusions over a range of doses, the maximum serum concentration (Cmax) and the area under the curve (AUC) showed relative dose proportionality. The overall average half-life (t1/2) over the dosing interval was about 12 days. The pharmacokinetic profile of Campath administered as a 30 mg intravenous infusion three times per week was eva luated in CLL patients. Peak and trough levels of Campath rose durin |
