CLL-Irl Study. CTRIAL-IE (ICORG) 07-01, V7
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, 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 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 fludarabine
      together with cyclophosphamide and rituximab may kill more cancer cells.

      PURPOSE: This phase II trial is studying giving fludarabine together with cyclophosphamide
      and rituximab to see how well it works in treating patients with chronic lymphocytic
      leukemia.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Evaluate the efficacy, in terms of complete remission rate, of fludarabine phosphate,
           cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia.

      Secondary

        -  Determine the time to treatment failure (TTF) in these patients.

        -  Determine the overall survival of these patients until 10th January 2019.

        -  Assess the predictive value of immunophenotype, hypermutation analysis, and FISH in
           determining TTF and OS in these patients.

        -  Determine the safety profile of this regimen.

      OUTLINE: This is a multicenter study.

      Patients receive fludarabine IV over 30 minutes or orally and cyclophosphamide IV or orally
      on days 1-3 and pegfilgrastim subcutaneously on day 4. Starting on course 2, patients receive
      rituximab IV on day 1. Treatment repeats every 28 days for up to 6* courses in the absence of
      disease progression or unacceptable toxicity.

      NOTE: *Patients achieving negative minimal residual disease receive 4 courses of treatment.

      Blood samples are collected periodically for biomarker analysis. Samples are analyzed for
      protein expression (i.e., CD38, CD20, and ZAP70) by flow cytometry; quantitative
      immunoglobulins, β2-microglobulin, and T-cell subsets by electrophoresis; IgVH mutation
      status; and cytogenetics (i.e., +12, del 13q, del 11q, and del 17p) by FISH.

      After completion of study therapy, patients are followed every 6 months for 5 years and then
      annually until 10th January 2019.
    

Intervention name(s): pegfilgrastim; rituximab; cyclophosphamide; fludarabine phosphate; cytogenetic analysis; fluorescence in situ hybridization; gene expression analysis; mutation analysis; protein expression analysis; flow cytometry; laboratory biomarker analysis
Intervention type(s): Biological; Biological; Drug; Drug; Genetic; Genetic; Genetic; Genetic; Genetic; Other; Other
Intervention MeSH terms: Cyclophosphamide; Rituximab; Fludarabine; Fludarabine phosphate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: B-cell chronic lymphocytic leukemia; refractory chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia