The goal of this clinical research study is to learn if giving CAMPATH-1H first as an injection into a vein, then as an injection under the skin can shrink or slow the growth of the disease in patients with chronic lymphocytic leukemia (CLL) who have already received standard therapy. Another goal is to learn if the side effects related to CAMPATH-1H treatment are less severe by giving the drug first as an injection into a vein then as an injection under the skin.

The purposes of this trial are:

1. To evaluate the response rate (CR+PR) to CAMPATH-1H given as continuous infusion followed by subcutaneous injection in patients with previously treated CLL who have failed fludarabine therapy.
2. To evaluate whether CAMPATH-1H, given as a continuous infusion followed by subcutaneous injections to patients with previously treated CLL will improve tolerability of the agent and permit higher doses to be delivered through that route.
3. To evaluate the pharmacokinetics of CAMPATH-1H when given as a 24 hour continuous infusion followed by a subcutaneous injection.

Inclusion Criteria:

• Age >= 18 years (CLL does not occur in the pediatric population).
• Signed informed consent.
• World Health Organization (WHO) performance status of 0, 1, or 2.
• Patients with B-CLL who have received fludarabine and are either refractory to frontline therapy or have relapsed within six months from receiving fludarabine-based therapy. Patients previously treated with Campath-1H are eligible.
• Serum creatinine <= 2mg/dL, total bilirubin <= 2mg/dL, and SGPT <= 3x upper limit of normal (ULN) unless due to direct infiltration of the liver or kidney with malignant cells.

Exclusion Criteria:

• Past history of anaphylaxis, following exposure to rat or mouse derived CDR-grafted humanized monoclonal antibodies.
• Prior chemotherapy, immunotherapy, or hormonal therapy within 2 weeks prior to study start. Hormonal replacement therapy is permitted. Prior therapy with monoclonal antibodies for at least 4 weeks prior to study start.
• Pregnant or nursing women or any patient of childbearing age unwilling to practice an acceptable form of contraception.
• Patients with history of HIV positivity.
• Active secondary malignancy.
• Active uncontrolled infection or any major systemic or other illness that would, in the opinion of the investigator, interfere with the patient's ability to comply with the protocol, compromise patient safety or interfere with the interpretation of study results.