Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia

This multicenter phase 2 trial investigated safety and efficacy of a new immunochemotherapeutic regimen combining rituximab (9) and fludarabine (F) in patients with fludarabine- and anthracycline-naive chronic lymphocytic leukemia (CLL). The rationale for using R + F includes single-agent efficacy of both drugs, in vitro synergistin of R and F, and no apparent overlapping toxicity. Of 31 eligible patients with B-CLL enrolled, 20 were previously untreated and 11 relapsed. Treatment consisted of. fludarabine administered at standard doses (25 mg/m(2)/d; days 1-5, 29-33, 57-61, and 85-89) and rituximab (375 mg/m(2)/d) given on days 57, 85, 113,. and 151. Side effects such as fever, chills, and exanthema were generally mild (National Cancer Institute Common Toxicity Criteria [NCl-CTC] grade 1/2 in 48% and grade 3 and/or 4 in 3% of patients). Fever and chills, were mainly associated with the first rituximab infusion. Hematologic toxicity included neutropenia (grade 1 and/or 2 in 26%, grade 3 and/or 4 in 42%) and thrombocytopenia (grade 1 and/or 2 in 16%, grade 3 and/or, 4 in 9%). One patient,died of cerebral bleeding during prolonged thrombocytopenia after the second cycle of fludarabine. There were a total of 32 infections in 16 patients, none of which was fatal. The overall response rate (complete remission [CR] and partial remission. [OR]) was 87% (27 of 31. evaluable patients). In 20 previously untreated patients, 17 (85%) responded. Ten of 31 patients achieved CR (5 of 20 untreated; 5 of 11 pretreated; 9 of 21 Binet stage B, 1 of 10 Binet stage C). The median duration of response was 75 weeks. We conclude that the combination of rituximab and fludarabine is feasible and effective in patients with B-CLL. (C) 2002 by The American Society of Hematology.