A Randomised Evaluation of Molecular Guided Therapy for Diffuse Large B-cell Lymphoma With Bortezomib
REMoDL-B
1 other identifier
interventional
1,132
2 countries
109
Brief Summary
The aims of this study are:
- To evaluate the benefits of the addition of bortezomib to standard rituximab with cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) therapy in Diffuse Large B-cell Lymphoma (DLBCL).
- To determine whether molecular phenotype effects the benefits derived from the addition of bortezomib.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Apr 2011
Typical duration for phase_3
109 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 25, 2011
CompletedFirst Posted
Study publicly available on registry
March 29, 2011
CompletedStudy Start
First participant enrolled
April 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2015
CompletedApril 15, 2016
April 1, 2016
4 years
March 25, 2011
April 14, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival
2 years
Secondary Outcomes (8)
Overall survival
5 years
Event-free survival
5 years
Disease-free survival
5 years
Time to progression
5 years
Response duration
5 years
- +3 more secondary outcomes
Study Arms (2)
Arm A: R-CHOP
ACTIVE COMPARATORParticipants receive 6 cycles of conventional R-CHOP chemotherapy on a standard 21 day schedule: Rituximab 375mg/m2 intravenous Cyclophosphamide 750mg/m2 Intravenous Doxorubicin 50mg/m2 Intravenous Vincristine intravenous Prednisolone 100mg od orally
Arm B: RB-CHOP
EXPERIMENTALParticipants in this arm will receive 1 cycle of conventional R-CHOP chemotherapy, followed by 5 cycles of R-CHOP: Cyclophosphamide 750mg/m2 Intravenous Doxorubicin 50mg/m2 Intravenous Vincristine intravenous bortezomib - Intravenous Prednisolone 100mg od orally .
Interventions
Chemoimmunotheraphy
Chemoimmunotheraphy
Eligibility Criteria
You may qualify if:
- Histologically confirmed DLBCL, expressing CD20. Sufficient diagnostic material should be available to forward to Haematological Malignancies Diagnostic Service (HMDS) for gene expression profiling and central pathology review. Core biopsies are acceptable, however the molecular profiling success rate is inferior compared to larger surgically acquired tissue samples. Best diagnostic practice encourages investigators to seek the latter approach whenever clinically appropriate.
- Measurable disease of at least 15mm.
- Not previously treated for lymphoma and fit enough to receive combination chemoimmunotherapy with curative intent.
- Age \> 18 years.
- Stage IAX (bulk defined as lymph node diameter \> 10cm) to stage IV disease and deemed to require a full course of chemotherapy.
- ECOG performance status 0-2.
- Adequate bone marrow function with platelets \> 100x109/L; neutrophils \>1.0x109/L at study entry, unless lower figures are attributable to lymphoma.
- Serum creatinine \< 150μmol/L, measured or calculated creatinine clearance \> 30mls/min, serum bilirubin \< 35μmol/L and transaminases \< 2.5x upper limit of normal at the time of study entry, unless attributable to lymphoma.
- Cardiac function sufficient to tolerate 300mg/m2 of doxorubicin. A pre-treatment echocardiogram is not mandated, but recommended in patients considered at higher risk of anthracycline cardiotoxicity.
- No concurrent uncontrolled medical condition.
- Life expectancy \> 3 months.
- Adequate contraceptive precautions for all patients of child bearing potential.
- A negative serum pregnancy test for females of child bearing potential or those \< 2 years after the onset of the menopause.
- Patients will have provided written informed consent.
You may not qualify if:
- Previous history of treated or untreated indolent lymphoma. However newly diagnosed patients with DLBCL who are found to also have small cell infiltration of the bone marrow or other diagnostic material (discordant lymphoma) will be eligible.
- Diagnosis of primary mediastinal lymphoma
- Uncontrolled systemic infection.
- History of cardiac failure of uncontrolled angina.
- Clinical CNS involvement.
- Serological positivity for Hepatitis C, B or known HIV infection. Viral serological testing is not mandated for study entry, but considered standard of care. (• Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible. • Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible as one would normally monitor HBV DNA serially and add lamivudine if copy number became detectable. There is an interaction between lamivudine and bortezomib. Reactivation of latent infection has been reported with the use of bortezomib in this population (along obviously with the well recognised reactivation following R-CHOP). For these patient safety reasons, these patients should be excluded. • Patients who have protective titres of hepatitis B surface antibody (HBSAb) after vaccination are eligible. • Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing) will not be eligible.)
- Serious medical or psychiatric illness likely to affect participation or that may compromise the ability to give informed consent.
- Active malignancy other than fully excised squamous or basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix in the preceding 5 years.
- History of allergic reaction to substances containing boron or mannitol.
- Patient unwilling to abstain from green tea and preparations made from green tea as bortezomib may interact with these.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (109)
Kantonsspital Aarau
Aarau, Switzerland
Kantonsspital Liestal
Basel, Switzerland
Universitatsspital Basel
Basel, Switzerland
Ospedale Regionale Bellinzona e Valli (IOSI)
Bellinzona, Switzerland
Inselspital Bern
Bern, Switzerland
STSAG Thun
Bern, Switzerland
Spitalzenturm Oberwallis
Brig, Switzerland
Kantonsspital Graubunden
Chur, Switzerland
Luzerner Kantonsspital
Lucerne, Switzerland
Kantonsspital Olten
Olten, Switzerland
Kantonsspital St. Gallen
Sankt Gallen, Switzerland
Stadtspital Triemli
Zurich, Switzerland
UniversitatsSpital Zurich
Zurich, Switzerland
University Hospital Aintree
Aintree, United Kingdom
Monklands, Hairmyres and Whishaw Hospitals
Airdrie, United Kingdom
Antrim Area Hospital
Antrim, United Kingdom
Stoke Mandeville Hospital and Wycombe Hospital
Aylesbury, United Kingdom
Ysbyty Gwynedd Hospital
Bangor, United Kingdom
Basildon Hospital
Basildon, United Kingdom
North Hampshire & Basingstoke Hospital
Basingstoke, United Kingdom
Royal United Hospital
Bath, United Kingdom
Belfast City Hospital
Belfast, United Kingdom
Arrowe Park
Birkenhead, United Kingdom
Good Hope Hosptial
Birmingham, United Kingdom
Queen Elizabeth Hospital
Birmingham, United Kingdom
Sandwell General Hospital Birmingham
Birmingham, United Kingdom
Victoria Hospital
Blackpool, United Kingdom
Royal Bournemouth
Bournemouth, United Kingdom
Bradford Royal Infirmary
Bradford, United Kingdom
Queen's Hospital Burton
Burton-on-Trent, United Kingdom
West Suffolk Hospital
Bury St Edmunds, United Kingdom
Velindre Hospital
Cardiff, United Kingdom
Broomfield Hospital
Chelmsford, United Kingdom
Cheltenham General Hospital and Gloucestershire Royal Infirmary
Cheltenham, United Kingdom
Chesterfield Royal
Chesterfield, United Kingdom
St Richard's Hospital
Chichester, United Kingdom
Colchester General Hospital
Colchester, United Kingdom
University Hospital Coventry
Coventry, United Kingdom
Darent Valley Hospital
Dartford, United Kingdom
Royal Derby Hospitals
Derby, United Kingdom
Doncaster Royal Infirmary
Doncaster, United Kingdom
Ulster Hospital
Dundonald, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Queen Elizabeth Hospital, Gateshead
Gateshead, United Kingdom
Medway Maritime Hospital
Gillingham, United Kingdom
Beatson West of Scotland Cancer centre
Glasgow, United Kingdom
Diana Princess of Wales, Grimsby
Grimsby, United Kingdom
Harrogate District Hospital
Harrogate, United Kingdom
Hemel Hempstead General and Watford General
Hemel Hempstead and Watford, United Kingdom
Huddersfield Royal Infirmary
Huddersfield, United Kingdom
Castle Hill Hospital
Hull, United Kingdom
Raigmore Hospital
Inverness, United Kingdom
Kent and Canterbury Hospital
Kent, United Kingdom
Queen Elizabeth Hospital
Kings Lynn, United Kingdom
St James University Hospital
Leeds, United Kingdom
Lincoln County Hospital, Pilgrim Hospital, Grantham and District Hospital
Lincoln, United Kingdom
Royal Liverpool
Liverpool, United Kingdom
Barnet General Hospital
London, United Kingdom
Ealing Hospital
London, United Kingdom
Guy's Hospital
London, United Kingdom
Hammersmith Hospital
London, United Kingdom
Hillingdon Hospital
London, United Kingdom
King's College Hospital
London, United Kingdom
Northwick Park Hospital
London, United Kingdom
Princess Royal University Hospital
London, United Kingdom
QE Woolwich
London, United Kingdom
Royal Free Hospital
London, United Kingdom
St Bartholomews Hospital
London, United Kingdom
St George's Hospital
London, United Kingdom
St Helier Hospital
London, United Kingdom
The Royal Marsden
London, United Kingdom
University College Hospital London
London, United Kingdom
Luton and Dunstable Hospital
Luton, United Kingdom
Maidstone Hospital and The Tunbridge Wells Hospital
Maidstone, United Kingdom
Christie Hospital
Manchester, United Kingdom
Manchester Royal Infirmary
Manchester, United Kingdom
Wythenshawe Hospital
Manchester, United Kingdom
The James Cook University Hospital
Middlesbrough, United Kingdom
Milton Keynes General Hospital
Milton Keynes, United Kingdom
Freeman Hospital, Newcastle
Newcastle, United Kingdom
Northampton General Hospital
Northampton, United Kingdom
Mount Vernon Hospital
Northwood, United Kingdom
Nottingham City Hospital
Nottingham, United Kingdom
George Eliot Hospital
Nuneaton, United Kingdom
Royal Oldham
Oldham, United Kingdom
Churchill Hospital
Oxford, United Kingdom
Derriford Hospital
Plymouth, United Kingdom
Poole General Hospital
Poole, United Kingdom
Craigavon Area Hospital
Portadown, United Kingdom
Queen Alexandra Hospital
Portsmouth, United Kingdom
Royal Berkshire Hospital
Reading, United Kingdom
Glan Clwyd District General Hospital
Rhyl, United Kingdom
Queen's Hospital
Romford, United Kingdom
Salisbury District Hospital
Salisbury, United Kingdom
Scunthorpe General Hospital
Scunthorpe, United Kingdom
Royal Hallamshire Hospital
Sheffield, United Kingdom
Wexham Park
Slough, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
Southend Hospital
Southend, United Kingdom
County Hospital
Stafford, United Kingdom
Royal Stoke Hospital
Stoke, United Kingdom
Sunderland Royal Hospital
Sunderland, United Kingdom
Great Western Hospital
Swindon, United Kingdom
Torbay District General Hospital
Torbay, United Kingdom
Royal Cornwall Hospital
Truro, United Kingdom
Pinderfields Hospital, Dewsbury Hospital and Ponerfract Hospital
Wakefield, United Kingdom
Warwick Hospital
Warwick, United Kingdom
Worcestershire Royal Hospital
Worcester, United Kingdom
Worthing Hospital
Worthing, United Kingdom
Related Publications (2)
Davies AJ, Barrans S, Stanton L, Caddy J, Wilding S, Saunders G, Mamot C, Novak U, McMillan A, Fields P, Collins GP, Stephens R, Cucco F, Sha C, van Hoppe M, Tooze R, Davies JR, Griffiths G, Schuh A, Burton C, Westhead DR, Du MQ, Johnson PWM. Differential Efficacy From the Addition of Bortezomib to R-CHOP in Diffuse Large B-Cell Lymphoma According to the Molecular Subgroup in the REMoDL-B Study With a 5-Year Follow-Up. J Clin Oncol. 2023 May 20;41(15):2718-2723. doi: 10.1200/JCO.23.00033. Epub 2023 Mar 27.
PMID: 36972491DERIVEDDavies A, Cummin TE, Barrans S, Maishman T, Mamot C, Novak U, Caddy J, Stanton L, Kazmi-Stokes S, McMillan A, Fields P, Pocock C, Collins GP, Stephens R, Cucco F, Clipson A, Sha C, Tooze R, Care MA, Griffiths G, Du MQ, Westhead DR, Burton C, Johnson PWM. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019 May;20(5):649-662. doi: 10.1016/S1470-2045(18)30935-5. Epub 2019 Apr 1.
PMID: 30948276DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Prof Peter Johnson
University Hospital Southampton NHS Foundation Trust
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 25, 2011
First Posted
March 29, 2011
Study Start
April 1, 2011
Primary Completion
April 1, 2015
Study Completion
June 1, 2015
Last Updated
April 15, 2016
Record last verified: 2016-04
Data Sharing
- IPD Sharing
- Will share