Trial Information

Single-agent Rituximab as Maintenance Treatment Versus Observation After Combined Induction Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab (FCR) in Patients Older Than 65 Years With Previously Untreated B-cell Chronic Lymphocytic Leukemia (B-CLL): a Phase III Intergroup Trial of the GOELAMS and the FCGCLL/WM Groups

OBJECTIVES:

Primary

- To demonstrate superiority, in terms of 3-year progression-free survival (PFS), of
rituximab maintenance over observation in patients who are in complete or partial
response (CR or PR) after induction therapy comprising fludarabine phosphate,
cyclophosphamide, and rituximab.

Secondary

- To determine event-free survival, disease-free survival, overall survival, and time to
next treatment, all from time of randomization.

- To determine overall response rate (CR and PR) according to NCI criteria.

- To assess the rate of phenotypic response (minimal residual disease).

- To assess duration of phenotypic and NCI clinical responses.

- To determine response rates and time-related parameters in biological subgroups.

- To determine rates of treatment-related adverse events.

- To evaluate of CD4/CD8 counts, immunoglobulin levels, and incidence of Coombs-positive
hemolytic anemia.

- To study pharmacokinetics of rituximab during induction and maintenance.

- To evaluate the prognostic impact of the immunoglobulin FcγRIIIA genotype.

- To assess quality of life.

- To study pharmacoeconomics.

OUTLINE: This is a multicenter study. Patients are stratified according to response to
induction therapy (complete response [CR] vs partial response [PR]), IgV_H mutational
status, and 11q deletion.

Patients receive rituximab IV on days 1 and 14 of courses 1-2 and on day 1 of courses 3 and
4. Patients also receive oral fludarabine phosphate and oral cyclophosphamide once daily on
days 2-4 of course 1 and on days 1-3 of courses 2-4. Courses repeat every 28 days. Patients
achieving CR or PR are randomized to 1 of 2 maintenance arms once they have recovered from
toxicities.

- Arm A: Patients receive rituximab IV on day 1. Treatment repeats every 2 months in the
absence of disease progression for a maximum duration of 24 months (12 infusions).

- Arm B: Patients undergo observation only. Patients undergo lymphocyte sample collection
for biological studies including diagnostic immunophenotyping, Matutes score (with
CD38, CD20, and CD43) , ZAP-70 analysis, standard karyotyping, cytogenetic screening by
FISH (17p13 deletion, 11q22 deletion, 13q14 deletion, and trisomy 12), IgV_H mutational
status, serum thymidine kinase, FcγRIIIA genotyping, and pharmacokinetic study. Samples
are frozen and stored for later studies.

After completion of study therapy, patients are followed every 3 months for 1 year and then
every 6 months for up to 4 years.