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