Campath-1H Plus Rituximab for CD52- and CD20- Positive Refractory or Relapsed Chronic Lymphoid Disorders
Campath-1H Plus Rituximab for CD52- and CD20- Positive Refractory or Relapsed Chronic Lymphoid Disorders
The goal of this clinical research study is to learn if giving CAMPATH-1H with rituximab can
 shrink or slow the growth of the disease in patients with chronic lymphoid disorders that
 have either not responded or whose disease has returned after treatment with standard
 therapies.
Objectives:

 1. To determine the efficacy and response rates of Campath-1H when given as a continuous
 intravenous infusion followed by subcutaneous injection plus rituximab in the treatment
 of chronic lymphoid disorders that are refractory to conventional therapy, have
 relapsed, or have no established frontline therapy.

 2. To assess the safety of the combination of Campath-1H when given as a continuous
 intravenous infusion followed by subcutaneous injection plus rituximab in chronic
 lymphoid disorders that express both CD52 and CD20 cell surface antigens.

 3. To measure levels of soluble (s) CD20 and sCD52 as well as levels of Campath-1H,
 rituximab and antibody complexes of rituximab/CD20 and Campath-1H/CD52 in patients with
 chronic lymphoid disorders treated with Campath-1H plus rituximab.
Inclusion Criteria:

 1. Age >/=15 years.

 2. Written informed consent.

 3. Patients with chronic lymphoid malignancies that are either refractory to frontline
 therapy or have relapsed and that have a predicted probability of response of less
 than 20% with conventional therapy or allogeneic/autologous stem cell transplantation.

 4. The following histologies are included: B-cell chronic lymphocytic leukemia (B-CLL or
 B-cell CLL), B-cell prolymphocytic leukemia (PLL), chronic lymphoid leukemia
 (CLL/PLL), hairy cell leukemia and hairy cell variant, mantle cell leukemia/lymphoma,
 marginal zone lymphoma/leukemia, splenic lymphoma with villous lymphocytes, CLL with
 evidence of transformation (e.g., Richter's transformation), large granular
 lymphocytic leukemia (LGL and NK-cell type).

 5. Patients with above mentioned histologies whose malignant cell population have
 expressed both CD52 and CD20 in >/= 20% of cells as assessed by flow cytometry or
 immunohistochemistry. Expression of CD20 or CD52 < 20% is permitted if patients
 received rituximab or alemtuzumab, respectively, within 3 months prior to study start.

 Exclusion Criteria:

 1. Patients who have previously received Rituximab and CAMPATH-1H in combination are
 excluded.

 2. ECOG performance status of </= 2.

 3. Serum creatinine </= 2mg/dL and total bilirubin of £ 2 mg/dL unless due to direct
 infiltration of the liver or kidney with malignant cells.

 4. Patients with a past history of anaphylaxis following exposure to rat or mouse derived
 CDR-grafted humanized monoclonal antibodies are excluded <CDR = complementarity
 determining regions>.

 5. Negative pregnancy test (serum or urine) if female and of childbearing potential only
 (non-childbearing is defined as greater than one year post-menopausal or surgically
 sterilized).

 6. No prior chemotherapy, immunotherapy, or hormonal therapy within 2 weeks prior to
 study start. Hormonal replacement therapy is permitted. No prior therapy with
 monoclonal antibodies for at least 4 weeks prior to study start.

 7. Patients at high risk of hepatitis B virus (HBV) infection and active HBV infection
 are excluded.