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A Phase II Study of Fludarabine, Cyclophosphamide and Rituximab as Initial Therapy in Chronic Lymphocytic Leukaemia

Phase 2
64 Years
Open (Enrolling)

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Trial Information

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.

Inclusion Criteria


- Diagnosis of chronic lymphocytic leukemia

- Stage I-IV disease (Binet stage progressive A, B, C)

- CD5 and CD23 positive

- Untreated OR relapsed/resistant disease after combination chemotherapy or

- No 17p deletion


- WHO performance status 0-2

- Life expectancy > 1 year

- Creatinine clearance ≥ 50 mL/min

- HIV negative

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other concurrent malignancy except for noninvasive cervical cancer or localized
nonmelanomatous skin cancer

- No history of anaphylaxis to mouse-derived humanized monoclonal antibody

- No other severe concurrent (e.g., cardiac or pulmonary) diseases or mental disorders
that could interfere with ability to participate in the study


- See Disease Characteristics

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete remission rate by NCI response criteria and minimal residual disease (MRD) analysis

Outcome 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.

Safety Issue:


Principal Investigator

Elisabeth Vandenberghe, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

St. James's Hospital, Ireland


Ireland: Irish Medicines Board

Study ID:




Start Date:

August 2008

Completion Date:

Related Keywords:

  • Leukemia
  • 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
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid