R2W: Randomised phase 2 trial in Waldenstrom macroglobulinaemia
Research type
Research Study
Full title
Subcutaneous Bortezomib, Cyclophosphamide and Rituximab (BCR) versus Fludarabine, Cyclophosphamide and Rituximab (FCR) for initial therapy of Waldenstrom macroglobulinaemia: a randomised phase II study.
IRAS ID
94789
Contact name
Rebecca Auer
Sponsor organisation
University College London
Eudract number
2011-005156-34
Clinicaltrials.gov Identifier
Research summary
Waldenstrom macroglobulinaemia (WM) is a low grade non-Hodgkin lymphoma characterised by bone marrow infiltration and the presence of an abnormal protein in the blood (IgM paraprotein) which contributes to the symptoms of WM by increasing the blood??s viscosity (hyperviscosity). WM is rare with an estimated 600 new cases per year in the UK. Very few randomised trials have been performed in WM partly due to the low incidence. Most patients require treatment at presentation but there is no agreed standard of first line therapy. Current treatment is unsatisfactory with responses often incomplete and slow to attain, while recurrence is inevitable. Median survival is approximately 5 years. R2W is a randomised, non-comparative phase II trial of subcutaneous bortezomib, cyclophosphamide, rituximab (BCR - experimental arm) versufluarabine, cyclophosphamide, rituximab (FCR - control arm) for initial therapy of WM. The overall aim of the study is to examine the safety and efficacy of the proposed BCR regimen and to determine whether it warrants further investigation in a randomised phase III setting. This is a two stage trial. Six patients will be treated initially with BCR to assess safety. If BCR is considered tolerable, a further 50 patients will be randomised between BCR and FCR (2:1) in the second stage of the trial. Patients will receive 3 cycles of treatment and then be reassessed. Those with evidence of progression will stop trial treatment. All other patients will continue with a further 3 cycles (to a total of 6) unless there is a clear clinical contra-indication to further treatment. Integral to this trial is to determine whether response assessment can be improved. Detailed response assessment will be performed after each cycle using peripheral blood samples to investigate whether responses can be predicted early without the need for repeated bone marrow samples.
REC name
London - City & East Research Ethics Committee
REC reference
12/LO/1168
Date of REC Opinion
9 Aug 2012
REC opinion
Favourable Opinion