CLL6 (Roche): a randomised, phase II trial of fludarabine, cyclophosphamide and rituximab (FCR) with or without mitoxantrone in previously untreated chronic lymphocytic leukaemia

INTERVENTION: This trial aims to recruit 218 patients over 18 months. Patients will be randomised to receive six cycles of either FCR or FCM‐R. Cycles of FCR and FCM‐R are reported every 28 days for a total of six courses. Each cycle is repeated every 28 days. However treatment is administered during each cycle as per the following schedule: Patients randomised to receive fludarabine, cyclophosphamide and rituximab (FCR) will receive: Fludarabine (oral): 24 mg/m^2/day on days 1 to 5 Cyclophosphamide (oral): 150 mg/m^2/day on days 1 to 5 Rituximab (IV): 375 mg/m^2 on day 1 (cycle 1) Rituximab (IV): 500 mg/m^2 on day 1 (cycle 2 to 6) Patients randomised to receive fludarabine, cyclophosphamide, rituximab and mitoxantrone (FCM‐R) will receive: Fludarabine (oral): 24 mg/m^2/day on days 1 to 5 Cyclophosphamide (oral): 150 mg/m^2/day on days 1 to 5 Rituximab (IV): 375 mg/m^2 on day 1 (cycle 1) Rituximab (IV): 500 mg/m^2 on day 1 (cycle 2 to 6) Mitoxantrone (IV): 6 mg/m^2/day on day 1 CONDITION: Chronic lymphocytic leukaemia (CLL) ; Cancer ; Lymphoid leukaemia PRIMARY OUTCOME: Proportion of patients achieving a complete response (CR) at three months post end‐of‐treatment as specified by the IWCLL criteria SECONDARY OUTCOME: 1. Proportion of patients with undetectable minimal residual disease, measured at three months post‐end‐of‐treatment; 2. Overall response rate defined as complete or partial remission by the IWCLL criteria, measured at three months post‐end‐of‐treatment ; 3. Progression free survival at two years ; 4. Overall survival at two years ; 5. Safety and toxicity, measured at two years after randomisation INCLUSION CRITERIA: 1. Both males and females, at least 18 years old 2. B‐cell chronic lymphocytic leukaemia (B‐CLL) with a characteristic immunophenotype 3. Binet's Stages B, C or Progressive A 4. Requirement for therapy as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria (must meet one of the following criteria: evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia) 5. Massive (i.e. 6 cm below the left costal margin) or progressive or symptomatic splenomegaly 6. Massive nodes (i.e. 10 cm in longest diameter) or progressive or sypmtomatic lymphodenopathy 7. Progressive lymphocytosis with an increase of more than 50% over a 2‐month period or lymphocyte doubling time (LDT) of less than 6 months as long as the lymphocyte count is over 30 x 10^9/L 8. A minimum of any one of the following disease‐related symptoms must be present: 8.1. Unitentional weight