• Objective response rate as measured by percentage after pentostatin, cyclophosphamide, and rituximab (PCR) and Campath at 6 months and 12 months [ Designated as safety issue: No ]
  
• Level of residual disease as measured by bone marrow and imaging studies at 6 months and 12 months [ Designated as safety issue: No ]
  

• Toxicity as measured by CTCAE criteria every month [ Designated as safety issue: Yes ]
  
• Overall survival and progression-free survival as measured by Kaplan-Meier method during study treatment [ Designated as safety issue: No ]
  
• Conversion rate of complete remission after Campath therapy in partial remission patients as measured by the percent improvement rate after Campath [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the objective response rate (complete remission, partial remission [PR], or nodular PR) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab (PCR) followed by alemtuzumab.
• Determine the presence of minimal residual disease in patients treated with this regimen.

Secondary

• Determine the toxicity of this regimen in these patients.
• Determine the overall and progression-free survival of patients treated with this regimen.
• Determine the number of patients who, after PCR, only achieve PR, stable disease, or progressive disease and subsequently convert to a higher response category after alemtuzumab.
• Correlate V_H gene mutation status and CD38 expression of the CLL B-cell clones with clinical outcome in patients treated with this regimen.
• Correlate the differential expression of genes in the leukemic cells with clinical outcome in patients treated with this regimen.
• Correlate surface phenotype and genetic defects of the CLL B-cell clones with clinical outcome and gene expression patterns in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Pentostatin, cyclophosphamide, and rituximab (PCR)* therapy: Patients receive pentostatin IV over 10-30 minutes, cyclophosphamide IV over 30-60 minutes, and rituximab** IV on day 1. Patients also receive filgrastim (G-CSF) or pegfilgrastim subcutaneously (SC) beginning on day 3 and continuing until blood counts recover. Treatment repeats every 28 days for a total of 6 courses in the absence of unacceptable toxicity.

NOTE: *Patients demonstrating progression while receiving PCR must have completed 2 courses of PCR prior to proceeding to alemtuzumab therapy

NOTE: **Patients receive rituximab IV on days 1, 3, and 5 for course 1 only; for courses 2-6, patients receive rituximab on day 1 only

Alemtuzumab therapy: Twelve weeks after completion of PCR therapy, patients receive alemtuzumab SC on days 1, 3, and 5. In the absence of disease progression or unacceptable toxicity, treatment repeats weekly for 4 weeks for patients with complete remission or nodular partial remission (PR) after PCR OR for 18 weeks for patients with PR, stable disease, or progressive disease after PCR.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 26-110 patients will be accrued for this study within 1.5 years.