RATIONALE: Drugs used in chemotherapy, such as pentostatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as alemtuzumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving pentostatin together with alemtuzumab and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving pentostatin together with alemtuzumab and rituximab works in treating patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

OBJECTIVES:

Primary

• To assess the rate of complete and overall response in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma treated with pentostatin, alemtuzumab, and low-dose rituximab.
• To monitor and assess toxicity of this treatment regimen.

Secondary

• To determine the overall and progression-free survival, duration of response, and time to next treatment.
• To assess the correlation between individual prognostic markers (17p-, 11q-, unmutated VH gene, VH3-21, ZAP-70+, CD38+, CD49d, and β2 microglobulin, miRNA profiles, angiogenesis status, and karyotypes of CpG stimulated cells) and clinical outcome.

OUTLINE: This is a multicenter study.

• Course 1: Patients receive pentostatin IV on days 8 and 22; alemtuzumab subcutaneously (SC) on days 3-5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; and sargramostim (GM-CSF) SC on days 10-14 and 24-28. Patients then proceed to course 2.
• Courses 2 and 3: Patients receive pentostatin IV on days 1 and 15; alemtuzumab SC and rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; and GM-CSF SC on days 3-7 and 17-21. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).

Treatment continues in the absence of disease progression or unacceptable toxicity.

Blood is collected on days 1, 3, 8, and 10 of course 1 for monoclonal antibody studies. Samples are analyzed for serum concentration of alemtuzumab and rituximab by ELISA and PCR; CH50 assay; complement activation and cytokine levels by ELISA; NK cell activation; and NK cell phenotype by immunofluorescent staining and flow cytometry.

After completion of study treatment, patients are followed up monthly for 6 months, every 3 months for 6 months, and then every 6-12 months for up to 5 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) meeting the following criteria:

  • Minimum threshold peripheral blood lymphocyte count of 5 x 10^9/L (CLL variant) OR adenopathy > 1 cm or palpable splenomegaly (SLL variant)

  • Immunophenotypic demonstrations of a population of B lymphocytes (as defined by CD19+) that are monoclonal (by light chain exclusion) AND have ≥ 3 of the following characteristics:

    • CD5+
    • CD23+
    • Dim surface light chain expression
    • Dim surface CD20 expression
    • FISH analysis is negative for IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression

• Must have progressive disease as indicated by any of the following characteristics (based on standard criteria for treatment):

  • Symptomatic CLL characterized by any of the following:

    • Weight loss > 10% within the past 6 months
    • Extreme fatigue
    • Fevers > 38.5° C (not due to infection)
    • Drenching night sweats without evidence of infection

  • Evidence of progressive bone marrow failure with hemoglobin < 11 g/dL or platelet count < 100 x 10^9/L

  • Massive and progressive splenomegaly (> 6 cm below left costal margin)

  • Massive (> 10 cm) or rapidly progressive lymphadenopathy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3
• Creatinine ≤ 2 times upper limit of normal (ULN)
• Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 times ULN
• AST ≤ 3.0 times ULN (unless due to hemolysis or CLL)
• Willing to provide mandatory blood samples for research studies
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 12 months after completion of study treatment
• No other active primary malignancy that requires treatment or limits survival to ≤ 2 years
• No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
• No New York Heart Association class III or IV heart disease
• No myocardial infarction within the past month
• No uncontrolled infection
• No HIV infection or AIDS
• No active hepatitis B infection (i.e., HBsAg or HBeAg positivity) or hepatitis C infection by serology
• No other comorbid condition

PRIOR CONCURRENT THERAPY:

• No more than 3 prior treatment regimens for CLL that included purine analogue drugs (e.g., fludarabine, pentostatin, or cladribine) OR previously untreated CLL in patients with high-risk disease due to 17p13 deletion on FISH analysis
• More than 4 weeks since prior major surgery
• More than 2 months since prior alemtuzumab
• Prior corticosteroids allowed
• No concurrent continuous systemic corticosteroids