DRUG STUDY AND INFORMATION FORM Generic Name: Alemtuzumab Trade Name: Campath Drug Class: Monoclonal Antibody

(Unarmed) Structure/Chemistry: Humanized IgG- monoclonal antibody composed of a rat antigen-binding region with human constant regions and variable framework.

Pharmacodynamics

Mechanism of Action: Binds to CD52 antigen present on the surface of a subset of normal neutrophils and on all B and T lymphocytes, on testicular elements and sperm, and on most Band T-cell lymphomas (highly expressed).

Pharmacologic Effects: Induces tumor cell death by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity

Drug Resistance or Tolerance:

Pharmacokinetics

Absorption: Given IV in dosages of 30 mg/day three times per week. Premedication with diphenhydramine (50 mg) and acetaminophen (650 mg) should precede drug infusion. Drug doses gradually increased to reduce the likelihood of hypersensitivity reactions. Distribution:

Elimination: initial t1/2 of 1 hour but after multiple doses t1/2 extends to 12 hours

Metabolism:

Adverse Side Effects/Toxicity: Most concerning toxicities are an acute infusion reaction and depletion of normal neutrophils and T cells. Serious myelosuppression with depletion of all blood lineages may represent bone marrow toxicity or auto-immune responses. Immunosuppression may lead to opportunistic infections, particularly in patients receiving purine analogs. CD4+ counts may remain profoundly depleted (<200 cells/ L) for up to a year. Patients should receive antibiotic prophylaxis against Pneumocystis carinii and herpes virus during treatment and for two months afterward. Patients should be monitored for viremia, hepatitis, and pneumonia. Drug Interactions: Alemtuzumab does not combine well with chemotherapy in standard regimens due to significant infectious complications.

Therapeutic uses: B- and T-cell low-grade lymphomas and CLL (chronic lymphocytic leukemia)

Miscellaneous: Monoclonal antibodies with names ending in ximab have chimeric (mouse/human) antibodies while those with names ending in umab have fully humanized antibodies.