RESPeCT: Revlimid Early Stage Poor Prognosis Chronic Lymphocytic Leukaemia (CLL) Trial
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Single Arm Phase II Study to Investigate the Use of Lenalidomide in the Treatment of Patients With Early Stage CLL Associated With Poor Prognostic Factors|
- Complete Remission with clearance of Minimal Residual Disease (MRD) [ Time Frame: 6 months (or earlier if clinically indicated) ] [ Designated as safety issue: No ]
- Event free survival [ Time Frame: Treatment/ progression/ death details collected at all visits (6 visits per month in dose escalation, 1 visit per month in dose maintenance, annual in long-term follow-up) ] [ Designated as safety issue: No ]Defined as interval from the first treatment day to the first sign of disease progression, treatment for relapse or death (whichever occurs first).
- Safety & tolerability of treatment (occurrence of adverse events) [ Time Frame: Assessed at all visits (6 visits per month in dose escalation, 1 visit per month in dose maintenance, annual in long-term follow-up) ] [ Designated as safety issue: Yes ]Adverse events will be monitored according to NCI CTCAE v3 from screening until 1 month after treatment discontinuation/ trial closure. Adverse event data will be captured at all visits (6 visits per month in dose escalation, 1 visit per month in dose maintenance). Adverse event data will be assessed by blood tests, physical exam/ vital signs and pregnancy testing.
- Time to next treatment [ Time Frame: Treatment details collected at all visits (6 visits per month in dose escalation, 1 visit per month in dose maintenance, annual in long-term follow-up) ] [ Designated as safety issue: No ]Defined as interval between first treatment day on the study protocol to the first day of the next course of CLL therapy following disease progression.
|Study Start Date:||May 2010|
|Study Completion Date:||December 2011|
|Experimental: Lenalidomide for early stage poor prognosis CLL||
Daily oral lenalidomide. Starting dose of 2.5mg daily, escalating to target dose of 10mg daily.
|The Royal Bournemouth Hospital|
|Bournemouth, Dorset, United Kingdom, BH7 7DW|
|Heart of England NHS Foundation Trust|
|Birmingham, United Kingdom, B9 5SS|
|Cambridge, United Kingdom, CB2 0QQ|
|University Hospital of Wales|
|Cardiff, United Kingdom, CF14 4XW|
|St James's University Hospital|
|Leeds, United Kingdom, LS9 7TF|
|The Royal Liverpool and Broadgreen University Hospital|
|Liverpool, United Kingdom, L7 8XP|
|King's College Hospital|
|London, United Kingdom, SE5 9RS|
|The Christie NHS Foundation Trust|
|Manchester, United Kingdom, M20 4BX|
|Mid Yorkshire Hospitals NHS Trust|
|Wakefield, United Kingdom, WF1 4DG|
|Principal Investigator:||Adrian Bloor||The Christie NHS Foundation Trust|