1. Randomised phase 2 trial in Waldenstrőm's macroglobulinaemia
R2W
Randomised phase 2 trial in Waldenstrőm's macroglobulinaemia
Subcutaneous Bortezomib, Cyclophosphamide and Rituximab (BCR) versus Fludarabine, Cyclophosphamide and Rituximab (FCR) for initial therapy of Waldenstrőm’s macroglobulinaemia (WM): a randomized phase II trial
OFF TRIAL
SAMPLE SIZE:
Stage I: 6 patients
Stage II: 50 (33 BCR; 17 FCR)
Total: patients
Assess response after 3 cycles
3 more cycles (total of 6)
unless clinical contraindication to further treatment exist
CR/VGPR/
PR/MR/SD
Progression
Follow-up
Response/progression assessed every 3 months for 5 years
Arm B: BCR (experimental)
Bortezomib 1.6mg/m2 s.c d1,8,15
Cyclophosphamide 250mg/m2 po d1,8,15
Rituximab (c2&5) 375mg/m2 d 1/8/15/22
Cycle repeated every 28 days
Arm A: FCR (control)
Fludarabine mg/m2 po d1-3
Cyclophosphamide 250mg/m2 po d1-3
No excess toxicity observed
Stage I: Safety run-in with BCR
Previously untreated patients with symptomatic WM with measurable IgM paraprotein
First 6 patients treated with BCR at 4 sites
Bortezomib 1.6mg/m2 s.c days 1, 8, 15
Cyclophosphamide 250mg/m2 po days 1, 8, 15
Rituximab (c2 & c5) 375mg/m2 iv days 1/8/15/22
Regular safety data monitoring
IDMC review after 6th patient reached C2 D1
Stage II: Randomisation BCR versus FCR 2:1
PATIENT ELIGIBILITY
Trial endpoints
MAIN INCLUSION CRITERIA
Age ≥ 18 years
WM with measurable IgM paraprotein
Previously untreated disease requiring therapy
Suggested criteria for initiating treatment include:
haematological suppression to Hb <10 g/dl, or neutrophils <1.5x109/l or platelets <150x109/l
clinical evidence of hyperviscosity
bulky lymphadenopathy and/or bulky splenomegaly
presence of B symptoms
No previous chemotherapy
Performance status grade 0 - 2
Life expectancy of greater than 6 months
MAIN EXCLUSION CRITERIA
Lymphoplasmacytic lymphoma with no detectable IgM
Severe pre-existing neuropathy (> grade 2)
Autoimmune cytopenias
Renal failure (creatinine clearance <30 ml/min)
Severe impairment of liver function: alkaline phosphatase/bilirubin >2.5xULN, ALT/AST >2.5xULN not related to lymphoma
Active systemic infection requiring treatment
Severe or life-threatening cardiac, pulmonary, neurological, psychiatric or metabolic disease
Please check protocol for further details
Overall response rate
Toxicity
Complete response rate
Speed and duration of response
Time to next treatment
Progression free survival
Overall survival
Quality of life
Samples requirements
during treatment & follow up
Serum for SFLC & Hevylite assays sent for analysis to a Central Lab
Peripheral blood for flow cytometry analysis at HMDS, Leeds
Bone marrow aspirate and trephine for analysis at HMDS, Leeds
Limited number of Sites for 1st safety stage:
Barts Health NHS Trust, London
Heart of England NHS Trust, Birmingham
Leeds Teaching Hospitals NHS Trust
University College London Hospitals NHS Trust
Chief investigator
Dr Rebecca Auer, St Barts
SITE ELIGIBILITY
Site registration form
R&D approval
Signed Clinical Trial Site Agreement
Delegation log
PI CV/GCP 
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R2W - Haematology Trials Group CR UK & UCL Cancer Trials Centre 90 Tottenham Court Rd, London, W1T 4TJ