Rituximab, Alemtuzumab, and GM-CSF As First-Line Therapy in Treating Patients With Early-Stage Chronic Lymphocytic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Alemtuzumab; Rituximab; Sargramostim
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Week 1 (dose escalation):
Day 3: 3mg subcutaneously; Day 4: 10mg subcutaneously; Day 5 30mg subcutaneously
Weeks 2-5:
30mg subcutaneously three times a week.; Weeks 2-5:
375 mg/m^2 by IV once weekly; Week 1-6:
250 mcg subcutaneously three time as week
Other intervention name(s): GM-CSF
Intervention MeSH terms: Rituximab; Alemtuzumab; Sargramostim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage 0 chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia