The majority of patients with CLL are diagnosed with early stage disease (Binet stage A or
Rai stage 0/I). Standard management of such patients is observation, and with median age at
diagnosis of 72 and median time to progression of >5-10 years, many will never require
treatment. In contrast, a proportion of patients have more aggressive disease, and over the
last decade, a number of molecular factors have been identified that may be used to identify
patients with poor prognosis disease . Each is associated with shortened time to treatment
(typically less than 3 years in patients with 2 of more factors), reduced survival, with in
the case of p53/ATM inactivation, resistance to treatment. Whether it is possible to improve
the outcome of patients with CLL and adverse prognostic factors by early intervention with
treatment is unknown. Several trials in the 1980's demonstrated that treatment of stage A CLL
with conventional chemotherapy (chlorambucil) did not alter the natural history of the
disease, although none of these studies stratified patients according to risk. The choice of
alternative potential therapeutic agents is limited; they should be effective in patients
with adverse prognostic factors, have acceptable toxicity, be able to overcome the drug
resistance associated with p53/ATM inactivation and ideally be orally administered. Two
recent phase II trials have demonstrated that Lenalidomide is effective in the treatment of
relapsed/refractory disease. Importantly, both studies included a high proportion of patients
with adverse prognostic factors including p53 inactivation. The principle objective of this
study is to investigate the efficacy of Lenalidomide in achieving disease response (complete
remission and clearance of minimal residual disease) in patients with poor risk early stage
disease, together with assessment of safety and tolerability.