Study of Subcutaneous Campath-1H in Patients With B-Cell CLL and Residual Disease After Chemotherapy

A Clinical Research Consortium (CRC) Phase II Study of Subcutaneous Campath-1H in Patients With B-Cell Chronic Lymphocytic Leukemia and Residual Disease After Chemotherapy

To evaluate whether CAMPATH-1H given to patients with CLL after maximum response to chemotherapy will: a) eliminate minimal residual disease (documented by flow cytometry) in patients who have achieved a complete remission (CR) or b) convert partial remission to complete remission.

To evaluate the time-to-progression of patients according to pretreatment characteristics and response status at study entry.

To evaluate whether CAMPATH-1H given to patients with CLL after maximum response to chemotherapy will eliminate minimal residual disease as determined by real-time quantitative PCR.

Approximately 95% of cases involve the clonal proliferation of B cells. Paraproteins, often of the IgM class, can be detected in the serum and/or urine of most patients with CLL. Unique cell surface markers are increasingly being used to diagnose the disease, and in approximately 40% of patients, cytogenetic abnormalities (for example, trisomy 12) can be found. Patients commonly present with lymphocytosis, lymphadenopathy, splenomegaly and symptoms of fatigue, weight loss, and malaise. In more advanced cases anemia and thrombocytopenia can also occur. The clinical course of CLL is unpredictable, with survival from initial diagnosis varying from 1 to 20 years (2). In addition, there is a subset of patients with indolent CLL whose absolute lymphocyte count is less than 30 x 109/L and who rarely die from the disease.

CLL is commonly staged according to the 5-point system proposed by Rai (Appendix B) and co-workers. While Rai staging is a relatively good predictor of overall survival, it cannot predict the prognosis in individual patients.

Inclusion Criteria:

• Male or female, at least 18 years old.
• Signed informed consent.
• Zubrod performance status of 0, 1, or 2 (Appendix C).
• Patients with CLL, CLL/PLL or PLL (prolymphocytic) who have achieved a clinical complete remission by NCI-WG criteria with chemotherapy, eg., alkylating agents, fludarabine or chemoimmunotherapy but have documentation of residual disease by immunophenotyping showing: (a) a residual population of CD5 and CD19 positive cells that comprise ≥ 10% of the marrow mononuclear cell population; or (b) a residual population of CD5 and CD19 positive cells that comprise <10% of the marrow mononuclear cells and have a Kappa/Lambda ratio >6 or <.33.
• Patients with CLL who have achieved a partial remission (PR) or nodular partial remission (nPR) by NCI-WG criteria after chemotherapy.
• Creatinine, bilirubin, AST or ALT and alkaline phosphatase ≤2 x the upper limit of normal.

Exclusion Criteria:

• Active infection.
• Past history of anaphylaxis, following exposure to rat or mouse derived CDR-grafted humanized monoclonal antibodies.
• Less than 2 months since prior chemotherapy.
• Previous treatment with CAMPATH-1H.
• Pregnant or nursing women.
• Patients on corticosteroids.
• Uncontrolled autoimmune hemolytic anemia.