Randomised Trial in Waldenstrom's Macroglobulinaemia

Waldenstrom macroglobulinaemia (WM) is a low grade nonHodgkin lymphoma characterised by bone marrow infiltration and the presence of an abnormal protein in the blood (IgM paraprotein. 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. The aim of this study is to find out whether a new combination of Bortezomib (Velcade®), Cyclophosphamide and Rituximab (MabThera), is well tolerated and effective for patients with WM. R2W is a randomised, noncomparative, phase II trial of subcutaneous bortezomib, cyclophosphamide, rituximab (BCR, experimental arm) versus fludarabine, cyclophosphamide, rituximab (FCR, control arm) for initial therapy of WM. This is a two stage trial where six patients will be treated initially with BCR to assess tolerability. 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 contraindication to further treatment.