A Phase II Study of Fludarabine, Cyclophosphamide and Rituximab as Initial Therapy in Chronic Lymphocytic Leukaemia
- Evaluate the efficacy, in terms of complete remission rate, of fludarabine phosphate,
cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia.
- Determine the time to treatment failure (TTF) in these patients.
- Determine the overall survival of these patients at 10 years.
- 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 for 5 years.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete remission rate by NCI response criteria and minimal residual disease (MRD) analysis
A formal assessment of response by NCI Criteria (Appendix 3) with the addition of assessment of minimal residual disease in the marrow and if relevant assessment of bulky disease by CT scanning will be made after 4 +/-6 courses of therapy.
Elisabeth Vandenberghe, MD
St. James's Hospital, Ireland
Ireland: Irish Medicines Board