Randomized Comparison of Cladribine with Cyclophosphamide and Fludarabine with Cyclophosphamide in Previously Untreated Progressive and Symptomatic Chronic Lymphocytic Leukemia: The Interim Analysis of PALG CLL3 Trial.

The efficacy and toxicity of cladribine (2-CdA) + cyclophsphamide (CY) - CC versus fludarabine (FA) + CY - FC were compared in previously untreated chronic lymphocytic leukemia (CLL) patients. The study was started in January 2004. Eligible patients were asigned to either 2-CdA 0,12mg/kg/d and CY 250mg/m²/d for 3 consecutive days or FA 25mg/m2/d and CY 250mg/m²/d also for 3 days. Courses were repeated at 28 days intervals or longer if myelosupression and/or infection developes for a maximum 6 courses. The response and toxicity criteria were those recommended by NCI SWG. Minimal residual disease (MRD) was evaluated by flow cytometry if complete response (CR) was achieved. As shown in the table, there were no significant differences in the rates of overall response (OR), CR, grade 3/4 thrombocytopenia, neutropenia and infections between the programmes. MRD negativity was obtained in 4 patients in CC arm and in 6 patients in FC arm (p=0.69). The death rate was similar in both groups, 2 (3.2%) and 6 (8.2%), respectively (p=0.19). The therapy related mortality was not observed. In conclusion, CC and FC programmes seem to have similar efficacy and toxicity in previously untreated CLL patients. The results of the interim analysis of PALG CLL3 trial justify continuation of this study.