CLL Trials in the United Kingdom the Medical Research Council CLL Trials 1, 2 and 3

Abstract

The MRC has conducted randomised trials in CLL sine 1978: CLL 1 (1978–84), 660 patients; CLL 2 (1984–90), 640 patients; CLL 3 (from June 1990), 90 patients. Centralised morphological diagnosis and membrane marker studies have allowed the exclusion of non-CLL disorders. Some of the treatment questions were repeated in more than one trial. Chlorambucil (chl) given intermittently was compared with the combination COP in CLL 1: no differences in survival or response were observed although the response rate (CR + PR) of COP rose from 53% to 73% when the dose of cyclophosphamide was doubled; CR + PR with chl was 62%. Chlorambucil was used with or without prednisolone (pred) in CLL 2 (stages B and C) and no differences were observed in either response rate (chl 74%; chl + pred 80%) or survival. Comparing all cases which in both trials were allocated to receive a combination including pred (241) or chl alone (248), no advantage in survival could be detected with the addition of pred to alkylating agents. Splenic irradiation (SI) (116 patients) was compared to Chlorambucil (136 patients) in both trials. Although a survival advantage for SI was suggested in CLL 1, this was not confirmed in CLL 2. A new trial, CLL 3, will be testing the addition of an anthracycline, epirubicin, to chl in stages B and C. The effect of early therapy with chl was compared with deferred (or no) treatment in CLL 1 (stages I and II static) and CLL 2 (Stage A). The combined results in 306 patients show a survival advantage for the deferred treatment group (2p = 0.05) when allowance was made for age, stage and sex. Analysis of causes of death indicates that the main difference between the randomised groups is the number of deaths attributed to CLL itself. There was no significant difference in the incidence of cancer between the two groups.