A Randomised Phase III Trial Comparing Intermittent with Continuous Treatment Strategies in chronic lymphocytic leukaemia (CLL)

Design

A prospective, multicentre, open-label, randomised, controlled, 2-arm, parallel-group, non-inferiority study to comparing an intermittent treatment strategy (experimental arm) with continuous treatment (control arm) with ibrutinib (or other BTK inhibitor) for patients with CLL who have responded well to treatment with the BTK inhibitor. Participants will be randomised on a 1:1 basis to an intermittent treatment strategy or continuous treatment.

Setting 100 NHS cancer centres experienced in diagnosis and management of CLL. Health technology being assessed

An intermittent treatment strategy of ibrutinib (or other BTK inhibitor) will be compared with continuous treatment. Participants randomised to intermittent treatment will cease treatment immediately following randomisation, and restart when the restart criteria are met. When treatment restarts, participants restart treatment with the same BTK inhibitor as they received initially at the standard dose until the treatment stop criteria are met.

The stopping and starting criteria are assessed locally every 3 months at standard clinic visits. Participants can stop and restart treatment multiple times until either the treatment strategy fails, they withdraw from the strategy, or the trial ends. Measurement of costs and outcomes Primary: time to strategy failure

Secondary: overall survival, toxicity and tolerability, cost effectiveness, quality of life, length of time off treatment in the intermittent treatment arm, time to next treatment for CLL and response to next treatment for CLL. Sample size

800 patients will be randomised over a 6-year period. We expect to be able to recruit 45% of patients from our front-line CLL trial FLAIR and 55% from relapsed/refractory patients. Project timeline Set up: 1-12 months Recruitment: 13-84 months, including recruitment feasibility assessment months 18-30 and interim analysis months 73-75

Follow up: 85-120 months Analysis: 121-123 months Long term survival: month 195