This is a phase III, multicentre, randomized, controlled, open, parallel group trial in patients with previously untreated CLL. A total of 754 participants will be randomized on a 1:1 basis to receive standard therapy with fludarabine, cyclophosphoamide and rituximab (FCR) or ibrutinib plus rituximab (IR)
Background: Chronic Lymphocytic Leukaemia (CLL) is the most common haematological malignancy in the UK. The most effective therapy for treating CLL is the combination of fludarabine, cyclophosphamide and rituximab (FCR). FCR is the standard therapy for patients who are fit for relatively intensive therapy however FCR is associated with significant early and late toxicity mainly with infections and bone marrow suppression. As knowledge of CLL increases new therapies are being developed to treat the disease and the most promising new approach uses therapies that target signalling through the Bcell
receptor (BCR) which is expressed on CLL cells and leads to CLL cell growth.
Bruton’s tyrosine kinase is a critical component of BCR signalling and inhibiting it by use of ibrutinib, a leading agent in the new class of therapies, leads to impressive response rates with minimal toxicity in patients with CLL who have not responded well to previous chemotherapy.
Aims: To assess whether fludarabine (F) and cyclophosphamide (C) in FCR therapy can be replaced by targeted therapy with ibrutinib (I) thereby improving response rates, duration of remission, progressionfree
and overall survival with reduced toxicity, in patients with previously untreated CLL.
The main aim of the study is to compare the effect on progressionfree
survival of IR with that of FCR.
Methods: This is a phase III, multicentre, randomised, controlled, open, parallel group trial in patients with previously untreated CLL comparing IR with the current standard treatment of FCR. The primary research question is to assess
whether IR is superior to FCR in terms of progressionfree survival. Secondary objectives are to assess overall survival, MRD negativity, response rates, safety and toxicity, quality of life and costeffectiveness.