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.

• Age ≥ 15 years.
• Written informed consent.
• 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.
• The following histologies are included: B-cell CLL, B-cell PLL, 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).

• 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 either rituximab and/or Campath-

  1H on different protocols but not in combination are eligible for the study.

• Patients who have previously received either Rituximab and CAMPATH-1H in combination are excluded.
• ECOG performance status of </= 2.
• Serum creatinine </= 2mg/dL and total bilirubin of </= 2 mg/dL unless due to direct infiltration of the liver or kidney with malignant cells.
• Patients with a past history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanized monoclonal antibodies are excluded.
• 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).
• 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.
• Patients at high risk HBV infection and active HBV infection are excluded.