An Open-label Phase II Study of the Efficacy and Safety of the Combination of Fludarabine, Cyclophosphamide and Rituximab in Patients With Chronic Lymphocytic Leukaemia Who Are Newly Diagnosed, Have Relapsed or Are Resistant to First-Line Treatment
Overview
- Phase
- Phase 2
- Intervention
- pegfilgrastim
- Conditions
- Leukemia
- Sponsor
- Cancer Trials Ireland
- Enrollment
- 52
- Locations
- 7
- Primary Endpoint
- Complete remission rate by NCI response criteria and minimal residual disease (MRD) analysis
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Fludarabine, Cylophosphamide and Rituximab
Intervention: pegfilgrastim
Fludarabine, Cylophosphamide and Rituximab
Intervention: rituximab
Fludarabine, Cylophosphamide and Rituximab
Intervention: cyclophosphamide
Fludarabine, Cylophosphamide and Rituximab
Intervention: fludarabine phosphate
Fludarabine, Cylophosphamide and Rituximab
Intervention: cytogenetic analysis
Fludarabine, Cylophosphamide and Rituximab
Intervention: fluorescence in situ hybridization
Fludarabine, Cylophosphamide and Rituximab
Intervention: gene expression analysis
Fludarabine, Cylophosphamide and Rituximab
Intervention: mutation analysis
Fludarabine, Cylophosphamide and Rituximab
Intervention: protein expression analysis
Fludarabine, Cylophosphamide and Rituximab
Intervention: flow cytometry
Fludarabine, Cylophosphamide and Rituximab
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Complete remission rate by NCI response criteria and minimal residual disease (MRD) analysis
Time Frame: 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.
Secondary Outcomes
- Overall survival(Until 10th January 2019)
- Time to treatment failure (TFF)(A clinical assessment of response will be made after 4 courses of therapy, Patients with evidence of progressive disease will stop therapy and will be deemed to have failed treatment.)
- Acute and chronic toxicity as assessed by NCI criteria(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.)
- Predictive value of immunophenotype, FISH, and hypermutation analysis in determining TTF and OS(See description)