Campath-1H Plus Rituximab for CD52- and CD20- Positive Refractory or Relapsed Chronic Lymphoid Disorders

Objectives:

• 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.
• 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.
• 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

• 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 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).
• 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

• Patients who have previously received 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 <CDR = complementarity determining regions>.
• 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 of hepatitis B virus (HBV) infection and active HBV infection are excluded.