Randomised Trial in Waldenstrom's Macroglobulinaemia
R2W
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
1 other identifier
interventional
60
1 country
30
Brief Summary
The purpose of this trial is to assess tolerability and efficacy of the Bortezomib, Cyclophosphamide and Rituximab combination as initial therapy for previously untreated patients with symptomatic Waldenstrom's macroglobulinaemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jan 2013
Longer than P75 for phase_2
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 3, 2012
CompletedFirst Posted
Study publicly available on registry
May 7, 2012
CompletedStudy Start
First participant enrolled
January 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
August 2, 2020
CompletedJune 18, 2021
June 1, 2021
4.2 years
May 3, 2012
June 17, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Disease response
Number and percentage of patients who achieve disease response
6 months (end of treatment)
Secondary Outcomes (4)
Toxicity of grade 3 or higher adverse event
Up to 6 months after treatment start
Progression free survival
up to 5 years after treatment start
Overall survival
up to 5 years after treatment start
Quality of life (EQ-5D score)
at 3 and 6 months after treatment start
Study Arms (2)
bortezomib, cyclophosphamide, rituximab
EXPERIMENTALBortezomib:1.6 mg/m2 s.c; days 1, 8, 15 of each cycle. Cyclophosphamide:250 mg/m2 oral; days 1, 8, 15 of each cycle. Rituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only. Cycle repeated every 28 days. After 3 cycles of treatment, patients are reassessed and 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 contradiction to further treatment exist.
fludarabine, cyclophosphamide, rituximab
ACTIVE COMPARATORFludarabine:40 mg/sq m, oral, days 1,2 and 3 of each cycle. Cyclophosphamide:250 mg/sq m; oral, days 1, 2 and 3 of each cycle. Rituximab: 375 mg/sq m i.v. infusion days 1, 8, 15 and 22 of cycles 2 and 5 only. Cycle repeated every 28 days.After 3 cycles of treatment, patients are reassessed and 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 contradiction to further treatment exist.
Interventions
1.6 mg/m2 subcutaneous bortezomib on days1, 8 and 15 of 28 days cycle
Cyclophosphamide:250 mg/sq m, oral, days 1, 8 and 15 of each cycle in the experimental arm. Cyclophosphamide:250 mg/sq m, oral, days 1, 2 and 3 of each cycle in the control arm.
Rituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only
Fludarabine: 40 mg/sq m, oral, days 1, 2 and 3
Eligibility Criteria
You may qualify if:
- Age ≥ 18 years
- Confirmed diagnosis of WM (according to consensus panel / WHO criteria) with measurable IgM paraprotein
- Previously untreated disease at any stage requiring therapy at the discretion of the treating physician. 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 (prior plasma exchange and steroids are permissible)
- Performance status grade 0 - 2
- Life expectancy of greater than 6 months
- Informed consent
- Agreed compliance with recommended contraceptive precautions where appropriate
You may not qualify if:
- Lymphoplasmacytic lymphoma with no detectable serum IgM paraprotein
- Severe pre-existing neuropathy (\> grade 2)
- Autoimmune cytopenias
- Evidence of active Hepatitis B or C infection (patients with evidence of past HepB infection may be eligible - see appendix 6)
- Serological positivity for HIV
- Pregnant or lactating women
- Life expectancy severely limited by other illness
- Renal failure (creatinine clearance \<30 ml/min)
- Severe impairment of liver function: alkaline phosphatase/bilirubin \>2.5 times upper limit of normal (ULN), ALT/AST \>2.5 times ULN not related to lymphoma (patients with Gilbert syndrome are eligible)
- 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 before day 1 of Cycle 1 with the exception of complete resection of basal cell carcinoma, squamous cell carcinoma of the skin or any other in situ malignancy
- Active systemic infection requiring treatment
- Concurrent treatment with another investigational agent
- Severe or life-threatening cardiac, pulmonary, neurological, psychiatric or metabolic disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (30)
Basingstoke & North Hampshire Hospital
Basingstoke, United Kingdom
Royal United Hospital
Bath, United Kingdom
Birmingham Heartlands Hospital
Birmingham, B9 5SS, United Kingdom
City Hospital
Birmingham, United Kingdom
Pilgrim Hospital
Boston, United Kingdom
Colchester General Hospital
Colchester, United Kingdom
Darent Valley Hospital
Dartford, United Kingdom
Dewsbury and District Hospital
Dewsbury, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Grantham and District Hospital
Grantham, United Kingdom
St James University Hospital
Leeds, LS9 7TF, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Lincoln County Hospital
Lincoln, United Kingdom
Royal Liverpool University Hospital
Liverpool, United Kingdom
St Bartolomew's Hospital
London, EC1A 7BE, United Kingdom
University College Hospital
London, NW1 2BU, United Kingdom
King's College Hospital
London, United Kingdom
Northwick Park Hospital
London, United Kingdom
Royal Free Hospital
London, United Kingdom
Maidstone Hospital
Maidstone, United Kingdom
Derriford Hospital
Plymouth, United Kingdom
Pontefract Hospital
Pontefract, United Kingdom
Queen's Hospital
Romford, United Kingdom
Tunbridge Wells Hospital
Royal Tunbridge Wells, United Kingdom
Salisbury District Hospital
Salisbury, United Kingdom
Musgrove Park Hospital
Taunton, United Kingdom
Torbay Hospital
Torquay, United Kingdom
Pinderfields Hospital
Wakefield, United Kingdom
Sandwell Hospital
West Bromwich, United Kingdom
Royal Hampshire County Hospital
Winchester, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rebecca Auer
St. Bartholomew's Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 3, 2012
First Posted
May 7, 2012
Study Start
January 1, 2013
Primary Completion
March 1, 2017
Study Completion
August 2, 2020
Last Updated
June 18, 2021
Record last verified: 2021-06