RATIONALE: Monoclonal antibodies, such as rituximab and alemtuzumab, 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. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving monoclonal antibody therapy together with GM-CSF may be an effective treatment for early-stage chronic lymphocytic leukemia.

PURPOSE: This phase II trial is studying the side effects of giving rituximab and alemtuzumab together with GM-CSF and to see how well it works in treating patients with early-stage chronic lymphocytic leukemia.

OBJECTIVES:

Primary

• To assess the rate of complete and overall response in patients with high-risk, early-stage, chronic lymphocytic leukemia (CLL) treated with alemtuzumab, rituximab, and sargramostim (GM-CSF).
• To monitor and assess toxicity of this regimen in these patients through clinical evaluation and serial monitoring of cytomegalovirus antigenemia by polymerase chain reaction (PCR).

Secondary

• To determine the overall and progression-free survival, time to response, time to next treatment, and duration of response in patients treated with this regimen.
• To assess the correlation between individual prognostic markers (i.e., 17p-, 11q-, unmutated VH gene, use of VH3-21, ZAP70+, CD38+) and clinical outcome.

Correlative Studies

• To assess response in these patients using an expanded definition of response, including minimal residual disease (MRD) by sensitive flow cytometry in patients in complete clinical remission.
• To assess MRD status of responding patients using sensitive flow cytometry and molecular assays (i.e., spectral karyotype analysis of CLL cells) before treatment and at relapse to identify subpopulations that could contribute to disease resistance and relapse.
• To detail the in vivo effect of this regimen on critical aspects of the immune system in CLL.
• To determine if GM-CSF, β-glucan, and CpG7909 can increase antibody dependent cellular cytotoxicity to improve efficacy against CLL cells and clinical response to treatment.

OUTLINE: Patients receive rituximab IV over 30 minutes on day 3 of weeks 2-5, alemtuzumab subcutaneously (SC) on days 3, 4, and 5 in week 1 and on days 1, 3, and 5 in weeks 2-5, and sargramostim SC on days 1, 3, and 5 in weeks 1-6. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection for measurement of serum cytomegalovirus DNA copy number by polymerase chain reaction at baseline, weekly during treatment, and monthly for the 6 months after completion of treatment. Patients also undergo bone marrow biopsy and aspirate at two months and then again at 12 months (if in complete remission). Blood samples are collected periodically during study for evaluation of prognostic biomarkers (i.e., 11q-, 17p-, unmutated IgVH gene, VH3-21 gene segment use, and CD38 and ZAP-70 expression) by fluorescent in situ hybridization (FISH) and for immunophenotyping by flow cytometry. Blood samples are collected from patients at the Mayo Clinic Rochester site at baseline and periodically during study for immunological and other correlative studies, including minimal residual disease (in responding patients only).

After completion of study therapy, patients are followed periodically for up to 5 years.

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL) meeting the following criteria:

  • Minimum threshold peripheral blood lymphocyte count 5 x 10^9/L

  • Monoclonality (light chain exclusion) of B lymphocytes detected by immunophenotyping (CD19-positive), demonstrating ≥ 3 of the following characteristics:

    • CD5-positive
    • CD23-positive
    • Dim surface light chain expression
    • Dim surface CD20 expression

  • Negative for IGH/CCND1 translocation AND/OR immunostaining is negative for cyclin D1 expression by fluorescent in-situ hybridization (FISH) analysis

  • Rai stage 0, I, or II disease that does not meet standard NCI-Working Group criteria for treatment of CLL

• Poor prognosis as defined by ≥ 1 of the following factors:

  • Unmutated IgVH mutation status AND CD38 expression (i.e., ≥ 30% cells positive on flow cytometry)
  • Unmutated IgVH mutation status AND ZAP-70 expression (i.e., ≥ 20% cells positive on flow cytometry)
  • VH3-21 gene segment use irrespective of mutation status AND CD38 expression (≥ 30% cells positive on flow cytometry)
  • VH3-21 gene segment use irrespective of mutation status AND ZAP-70 expression (≥ 20% cells positive on flow cytometry)
  • 11q-negative*
  • 17p-negative* NOTE: *Determination of IgVH mutation status is not required in patients whose eligibility is based on 17p13- or 11q22- deletions

PATIENT CHARACTERISTICS:

• ECOG performance status 0- 2

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 ULN

• AST ≤ 3.0 times ULN (unless due to hemolysis or CLL)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must practice effective contraception

• Willing to provide mandatory blood samples (for patients at the Mayo Clinic in Rochester only) for research studies as required by the protocol

• No comorbid conditions, including any of the following:

  • New York Heart Association Class III or IV heart disease
  • Myocardial infarction within the past month
  • Uncontrolled infection
  • HIV infection or AIDS
  • Serological evidence of active hepatitis B infection (i.e., serum antigen or e-antigen positivity) or positive hepatitis C serology

• No other active primary malignancy requiring treatment or limiting survival to ≤ 2 years

• No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior major surgery
• No prior chemotherapy or monoclonal antibody treatment for CLL
• No concurrent corticosteroids