Randomized Comparison of Cladribine Plus Cyclophsophamide with Fludarabine Plus Cyclophosphamide in Progressive Chronic Lymphocytic Leukemia: An Updated Report of Prospective PALG-CLL3 Study.

Purine analogues, Cladribine (2-CdA) and Fludarabine (FA), are highly effective in treatment of chronic lymphocytic leukemia (CLL). This prospective randomized phase 3 trial was designed to compare the efficacy and toxicity of 2-CdA and cyclophsophamide (CC regimen) with FA and cyclophsophamide (FC regimen) in previously untreated progressive CLL. The primary end points of the study were complete response (CR) and overall response (OR) after completion of the therapy. The secondary end points were progression free survival (PFS), overall survival (OS) and treatment related toxicity. Eligible patients were assigned to receive 6 courses of either 2-CdA 0.12 mg/kg/d i.v. with cyclophosphamide 250 mg/m²/d i.v. for 3 consecutive days or FA 25 mg/m²/d i.v. with cyclophosphamide 250 mg/m²/d i.v. for 3 consecutive days administered at 28 day intervals. The treatment response and toxicity were evaluated according to NCI-SWOG guidelines. The study started in January 2004, and here we present updated results from the interim analysis of 227 evaluated patients performed in July 2006. As shown in the table, there were no significant differences in the rates of CR and OR between the treatment groups. Moreover, the treatment related toxicity, including grade ¾ thrombocytopenia, neutroepenia and infections was similar in patients receiving FC or CC regimens. Median time of progression free survival did not differ between both groups (11.0 months in CC arm and 11.2 months in FC arm, p=0.41). There were 5 deaths (3.2%) observed in CC arm and 15 (8.1%) in FC arm. In conclusion, the preliminary results of our study indicate that CC and FC protocols have similar activity and toxicity in previously untreated patients with CLL.