A Phase II Trial to Evaluate the Efficacy and Safety of Subcutaneously Administered Alemtuzumab (CAMPATH®, MabCampath®) in Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia

Inclusion Criteria:

- A diagnosis of B-cell chronic lymphocytic leukemia (B-CLL); according to the National
Cancer Institute Working Group (NCI WG) Criteria.

- World Health Organization (WHO) performance status of 0, 1, or 2.

- Life expectancy ≥ 12 weeks.

- Previous therapy with at least one but no more than 5 regimens (single agent or
combination regimen). One therapy regimen is defined as consecutive, contiguous
cycles of the same drug(s) with no treatment interruptions lasting > 3 months.

- Patient requires treatment for CLL per the following criteria: -Rai stage III or IV;
-Rai stage 0-II with at least one of the following - evidence of progressive marrow
failure as manifested by the development of, or worsening of, anemia and/or
thrombocytopenia; Massive (i.e. greater than 6 cm below the left costal margin) or
progressive splenomegaly; Progressive lymphocytosis with an increase of greater than
50% over a 2-month period or an anticipated doubling time of less than 6 months;
Lymphocyte count > 100*10^9/L; B symptoms.

- More than 3 weeks since prior chemotherapy. Patient must have recovered from the
acute side effects incurred as a result of previous therapy.

- More than 3 weeks since using investigational agents. Patient must have recovered
from the acute side effects incurred as a result of previous therapy.

- Serum creatinine and conjugated (direct) bilirubin less than or equal to 2 times the
institutional upper limit of normal (ULN) unless secondary to direct infiltration of
the liver with CLL.

- Female patients with childbearing potential must have a negative pregnancy test
(serum or urine) within 2 weeks of first dose of study drug(s). All patients must
agree to use an effective contraceptive method while on study treatment, if
appropriate, and for a minimum of 6 months following study therapy.

- Signed, written informed consent (in the US, includes The Health Insurance
Portability and Accountability Act of 1996 (HIPAA) authorization)

Exclusion Criteria:

- Positive Coombs test and evidence of active hemolysis.

- Platelet count less than 50*10^9/L without splenomegaly.

- History of anaphylaxis following exposure to rat or mouse derived CDR-grafted
humanized monoclonal antibodies.

- Previously treated with CAMPATH.

- Previous bone marrow transplant.

- Known central nervous system (CNS) involvement with B-CLL

- Active infection, including human immunodeficiency virus (HIV) positive.

- Active second malignancy.

- Recent documented history (within 2 years) of active tuberculosis (TB), current
active TB infection, currently receiving anti-tuberculous medication (e.g., INH,
rifampin, streptomycin, pyrazinamide, or others).

- Active hepatitis or a history of prior viral hepatitis B or hepatitis C, or positive
hepatitis B serologies. Patients with a positive hepatitis B surface antibody
(HBsAb) test with a documented history of prior hepatitis B immunization are eligible
as long as other criteria are met (i.e. negative tests for: hepatitis B surface
antigen (HBsAg), hepatitis B core antibody (HBcAb) and hepatitis C virus antibody
(HCVAb)).

- Other severe, concurrent diseases (e.g., cardiac or pulmonary disease), mental
disorders, or major organ malfunction (liver, kidney) that could interfere with the
patient ability to participate in the study.

- Pregnant or nursing women.

- Cytomegalovirus (CMV) positive by polymerase chain reaction (PCR) (above the level of
detection). A patient that is PCR positive will require treatment to reduce the
viral load to a non-detectable level; but such a patient may be considered for study
entry once the infection has been treated.

- Medical condition requiring chronic use of oral corticosteroids at a dose higher than
physiologic replacement.