Randomised phase 2 trial in WM - Subcutaneous Bortezomib, Clycophosphamide and Rituximab (BCR versus Fludarabine, Cyclophosphamide and Rituximab (FCR) for initial therapy of Waldenstr?m’s macroglobulinaemia (WM): a randomised phase II trial
Description
Design:
R2W is a randomised (2:1), non-comparative, multicentre, phase II trial of bortezomib, cyclophosphamide and rituximab (BCR – experimental) versus fludarabine, cyclophosphamide and rituximab (FCR – control) for initial therapy in patients with symptomatic untreated Waldenstrom’s macroglobulinaemia (WM); using a three-outcome design for the experimental arm.
Treatment:
Patients are treated with BCR or FCR (in accordance with the arm to which they are randomised) for 3 cycles when response to treatment is assessed. Those with evidence of progression stop trial treatment. All other patients continue with further 3 cycles (to a total of 6) unless a clear clinical contraindication to further treatment exists.
Key inclusion/exclusion criteria:
Inclusion
- Age ≥18 years
- Performance status 0-2
- Life expectancy >6 months
- Confirmed diagnosis of WM with measurable IgM paraprotein
- Previously untreated disease at any stage requiring therapy at the discretion of the treating physician
- No previous chemotherapy
Exclusion
- Lymphoplasmacytic lymphoma with no detectable serum IgM paraprotein
- Severe pre-existing neuropathy (> grade 2)
- Autoimmune cytopenias
- Evidence of active Hepatitis B or C infection, or HIV
- Pregnant or lactating women
- Life expectancy severely limited by other illness
- Inadequate renal and liver function
- History of allergic reaction to compounds containing boron or mannitol
- Known hypersensitivity to murine compounds
- Diagnosed or treated for a malignancy other than WM within 5 years (with exceptions)
- Active systemic infection requiring treatment
- Concurrent treatment with another investigational agent
- Severe or life-threatening cardiac, pulmonary, neurological, psychiatric or metabolic disease
Duration of recruitment:
3 years
Aim
The primary objective of the study is to make a preliminary examination of the efficacy and safety of the proposed Bortezomib, Cyclophosphamide and Rituximab regimen for previously untreated patients with Waldenstrom’s macroglobulinaemia and to determine whether this regimen warrants further investigation in the randomised phase III setting.