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Lymphoma, Large B-Cell, DiffusePhase 3REMoDL-BNCT01324596

A Randomised Evaluation of Molecular Guided Therapy for Diffuse Large B-cell Lymphoma With Bortezomib

A Phase 3 study testing Intravenous and Bortezomib in people with Lymphoma, Large B-Cell, Diffuse, run by University Hospital Southampton NHS Foundation Trust at 109 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Large B-Cell, Diffuse
What is being tested?
Intravenous and Bortezomib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,132 participants
Where
109 sitesin 2 countries
Study dates
Apr 2011to Jun 2015
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.)
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  • 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.

Trial locations and contacts

109 sites in 2 countries.

109 sites in 2 countries

United Kingdom96 sites

  • University Hospital Aintree

    Aintree

  • Monklands, Hairmyres and Whishaw Hospitals

    Airdrie

  • Antrim Area Hospital

    Antrim

  • Stoke Mandeville Hospital and Wycombe Hospital

    Aylesbury

  • Ysbyty Gwynedd Hospital

    Bangor

  • Basildon Hospital

    Basildon

  • North Hampshire & Basingstoke Hospital

    Basingstoke

  • Royal United Hospital

    Bath

  • Belfast City Hospital

    Belfast

  • Arrowe Park

    Birkenhead

  • Good Hope Hosptial

    Birmingham

  • Queen Elizabeth Hospital

    Birmingham

  • Sandwell General Hospital Birmingham

    Birmingham

  • Victoria Hospital

    Blackpool

  • Royal Bournemouth

    Bournemouth

  • Bradford Royal Infirmary

    Bradford

  • Queen's Hospital Burton

    Burton-on-Trent

  • West Suffolk Hospital

    Bury St Edmunds

  • Velindre Hospital

    Cardiff

  • Broomfield Hospital

    Chelmsford

  • Cheltenham General Hospital and Gloucestershire Royal Infirmary

    Cheltenham

  • Chesterfield Royal

    Chesterfield

  • St Richard's Hospital

    Chichester

  • Colchester General Hospital

    Colchester

  • University Hospital Coventry

    Coventry

  • Darent Valley Hospital

    Dartford

  • Royal Derby Hospitals

    Derby

  • Doncaster Royal Infirmary

    Doncaster

  • Ulster Hospital

    Dundonald

  • Royal Devon and Exeter Hospital

    Exeter

  • Queen Elizabeth Hospital, Gateshead

    Gateshead

  • Medway Maritime Hospital

    Gillingham

  • Beatson West of Scotland Cancer centre

    Glasgow

  • Diana Princess of Wales, Grimsby

    Grimsby

  • Harrogate District Hospital

    Harrogate

  • Hemel Hempstead General and Watford General

    Hemel Hempstead and Watford

  • Huddersfield Royal Infirmary

    Huddersfield

  • Castle Hill Hospital

    Hull

  • Raigmore Hospital

    Inverness

  • Kent and Canterbury Hospital

    Kent

  • Queen Elizabeth Hospital

    Kings Lynn

  • St James University Hospital

    Leeds

  • Lincoln County Hospital, Pilgrim Hospital, Grantham and District Hospital

    Lincoln

  • Royal Liverpool

    Liverpool

  • Barnet General Hospital

    London

  • Ealing Hospital

    London

  • Guy's Hospital

    London

  • Hammersmith Hospital

    London

  • Hillingdon Hospital

    London

  • King's College Hospital

    London

  • Northwick Park Hospital

    London

  • Princess Royal University Hospital

    London

  • QE Woolwich

    London

  • Royal Free Hospital

    London

  • St Bartholomews Hospital

    London

  • St George's Hospital

    London

  • St Helier Hospital

    London

  • The Royal Marsden

    London

  • University College Hospital London

    London

  • Luton and Dunstable Hospital

    Luton

  • Maidstone Hospital and The Tunbridge Wells Hospital

    Maidstone

  • Christie Hospital

    Manchester

  • Manchester Royal Infirmary

    Manchester

  • Wythenshawe Hospital

    Manchester

  • The James Cook University Hospital

    Middlesbrough

  • Milton Keynes General Hospital

    Milton Keynes

  • Freeman Hospital, Newcastle

    Newcastle

  • Northampton General Hospital

    Northampton

  • Mount Vernon Hospital

    Northwood

  • Nottingham City Hospital

    Nottingham

  • George Eliot Hospital

    Nuneaton

  • Royal Oldham

    Oldham

  • Churchill Hospital

    Oxford

  • Derriford Hospital

    Plymouth

  • Poole General Hospital

    Poole

  • Craigavon Area Hospital

    Portadown

  • Queen Alexandra Hospital

    Portsmouth

  • Royal Berkshire Hospital

    Reading

  • Glan Clwyd District General Hospital

    Rhyl

  • Queen's Hospital

    Romford

  • Salisbury District Hospital

    Salisbury

  • Scunthorpe General Hospital

    Scunthorpe

  • Royal Hallamshire Hospital

    Sheffield

  • Wexham Park

    Slough

  • Southampton General Hospital

    Southampton

  • Southend Hospital

    Southend

  • County Hospital

    Stafford

  • Royal Stoke Hospital

    Stoke

  • Sunderland Royal Hospital

    Sunderland

  • Great Western Hospital

    Swindon

  • Torbay District General Hospital

    Torbay

  • Royal Cornwall Hospital

    Truro

  • Pinderfields Hospital, Dewsbury Hospital and Ponerfract Hospital

    Wakefield

  • Warwick Hospital

    Warwick

  • Worcestershire Royal Hospital

    Worcester

  • Worthing Hospital

    Worthing

Other trials in United Kingdom

Switzerland13 sites

  • Kantonsspital Aarau

    Aarau

  • Kantonsspital Liestal

    Basel

  • Universitatsspital Basel

    Basel

  • Ospedale Regionale Bellinzona e Valli (IOSI)

    Bellinzona

  • Inselspital Bern

    Bern

  • STSAG Thun

    Bern

  • Spitalzenturm Oberwallis

    Brig

  • Kantonsspital Graubunden

    Chur

  • Luzerner Kantonsspital

    Lucerne

  • Kantonsspital Olten

    Olten

  • Kantonsspital St. Gallen

    Sankt Gallen

  • Stadtspital Triemli

    Zurich

  • UniversitatsSpital Zurich

    Zurich

Other trials in Switzerland

About this study

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.
Read the detailed description

REMoDLB is a trial which aims to determine whether the addition of bortezomib (a drug that blocks the action of cellular complexes that break down proteins) to standard combination chemotherapy (called R-CHOP) improves how long patients with diffuse large B cell lymphoma survive without a recurrence of the disease. Results from recent research have suggested that patients can be divided into two biologically distinct subgroups labeled GCB (germinal centre derived B-cells like) and ABC (activated peripheral B-cells like).

GCB patients tend to do well with standard combination chemotherapy, but ABC patients have the majority of treatment failures. It is thought that ABC patients will benefit most from the addition of bortezomib.

The trial will be discussed with the patient. They will be asked to consent to molecular profiling of their tumour block whilst they have some time to consider whether they wish to enter the main trial. This will allow more time for this sample to be analysed and their particular biological subgroup to be determined.

All patients consenting to enter the main study will be given an initial cycle of RCHOP chemotherapy. Within each subgroup (ABC or GCB) patients will be randomly assigned to receive either RCHOP or RCHOP and bortezomib to ensure that the same number of each biological subgroup will receive the two treatments. All patients will then have 5 cycles of their assigned treatment regimen (either RCHOP or RCHOP and bortezomib). All patients will be followed up for a period of five years once they have completed their chemotherapy. The GCB group receiving RCHOP and bortezomib will be regularly checked to see if the new treatment is improving survival without recurrence of the disease. If the addition of bortezomib is not found to be beneficial for this group of patients this part of the trial will be stopped and all GCB patients will receive the standard treatment only (RCHOP).

It is anticipated that between 560 and 892 patients will be randomly allocated to the two treatments, the exact number depends on whether the GCB group receiving RCHOP and bortezomib is stopped or not.

Being tested
Intravenous, Bortezomib
Keywords
Lymphoma, Large B-Cell, Diffuse, Bortezomib, R-CHOP, Molecular profiling, Chemotherapy
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IntravenousDrug

    Also called Rituximab, cyclophosphamide, doxorubicin, vincristine

    Chemoimmunotheraphy

  • BortezomibDrug

    Also called rituximab, cyclophosphamide, doxorubicin, vincristine

    Chemoimmunotheraphy

Study groups in NCT01324596
Study groupRoleWhat they receive
Arm A: R-CHOPActive 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
Receives: Drug: Intravenous
Arm B: RB-CHOPExperimentalParticipants 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 .
Receives: Drug: Bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival

    Measured: 2 years

Secondary outcomes (8)

  1. Overall survival

    Measured: 5 years

  2. Event-free survival

    Measured: 5 years

  3. Disease-free survival

    Measured: 5 years

  4. Time to progression

    Measured: 5 years

  5. Response duration

    Measured: 5 years

  6. Complete and overall response rates

    Measured: 5 years

  7. Evaluation of toxicity (according to CTCAE version 4.0)

    Measured: 5 years

  8. Quality of life and assessment of peripheral neuropathy

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2011 (estimated)
  2. Study startApr 2011
  3. Primary completionApr 2015
  4. Study completionJun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,132 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01324596
Sponsor's protocol ID
RHMCAN0749
Acronym
REMoDL-B
Status last verified
Apr 2016
First submitted
25 Mar 2011
Last updated
15 Apr 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes

Publications

  • 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.

    PubMed 36972491

  • Davies 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.

    PubMed 30948276

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Intravenous and Bortezomib in people with Lymphoma, Large B-Cell, Diffuse, run by University Hospital Southampton NHS Foundation Trust at 109 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 109 sites in United Kingdom, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01324596, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2016.

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