Condition category
Cancer
Date applied
30/03/2011
Date assigned
30/03/2011
Last edited
04/10/2011
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Mrs Christine May

ORCID ID

Contact details

University of Southampton Clinical Trials Unit
MP131
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Additional identifiers

EudraCT number

2010-022422-32

ClinicalTrials.gov number

Protocol/serial number

UKCRN ID: 9800

Study information

Scientific title

A Randomised Evaluation of Molecular guided therapy for Diffuse large B-cell Lymphoma with Bortezomib

Acronym

REMoDLB

Study hypothesis

This study of treatment for diffuse large Bcell lymphoma aims to determine whether adding bortezomib to standard combination chemotherapy and rituximab (RCHOP) can improve progression free survival. Molecular studies have indicated the heterogenous biology of this disease identifying two subgroups (ABC and GCB) and this knowledge will be applied prospectively to determine whether a subgroup of patients might benefit more from the addition of bortezomib. Patients will be randomised to one of two groups (RBCHOP or RCHOP) on the basis of their molecular subgroup.

Ethics approval

10/H0405/79; First MREC approval date 24/01/2011

Study design

Randomised trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Lymphoma; Disease: Lymphoma (non-Hodgkin's)

Intervention

RB-CHOP, Rituximab, Cyclophsophamide, vincristine, Prednisolone, Doxorubicin, Bortezomib; R-CHOP, Rituximab, Cyclophosphamide, Doxorubicin, Prenisolone, Vincristine; Follow Up Length: 60 month(s); Study Entry : Single Randomisation only

Intervention type

Drug

Phase

Phase III

Drug names

Bortezomib

Primary outcome measures

Progression-free survival; Timepoint(s): The primary endpoint is progression-free survival.

Secondary outcome measures

Disease-free survival; Timepoint(s): Disease-free survival will be measured from the time of documentation of disease-free state (CR or C; Event-free survival (time to treatment failure); Timepoint(s): Event-free survival (time to treatment failure) is measured from the day of registration to any trea; Overall survival; Timepoint(s): Overall survival will be measured from the day of registration to the date of death from any cause; Response duration; Timepoint(s): Response duration is defined as the time from documentation of response (ie,CR, CRu or PR) until the; Response Evaluation; Timepoint(s): Response will be assessed in accordance with the International Workshop Standardized Response Criter; Time to progression; Timepoint(s): Time to progression (TTP) is defined as the time from registration until documented lymphoma progres

Overall trial start date

13/04/2011

Overall trial end date

12/04/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. Histologically confirmed Diffuse large B-cell lymphoma (DLBCL), expressing CD20
2. Sufficient diagnostic material should be available to forward to Haematological Malignancy Diagnostic Service (HDMS) for gene expression profiling and central pathology review
3. Core biopsies are acceptable, however the molecular profiling success rate is inferior compared to larger surgically acquired tissue samples
4. Best diagnostic practice encourages investigators to seek the latter approach whenever clinically appropriate
5. Not previously treated for lymphoma and fit enough to receive combination chemoimmunotherapy with curative intent
6. Age >18 years
7. Stage IAX (bulk defined as lymph node diameter >10cm) to stage IV disease and deemed to require a full course of chemotherapy
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
9. Adequate bone marrow function with platelets >100x109/L; neutrophils >1.0x109/L at study entry, unless lower figures are attributable to lymphoma
10. 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
11. Cardiac function sufficient to tolerate 300mg/m2 of doxorubicin
12. A pre-treatment echocardiogram is not mandated, but recommended in patients considered at higher risk of anthracycline cardiotoxicity
13. No concurrent uncontrolled medical condition
14. Life expectancy >3 months
15. Adequate contraceptive precautions for all patients of child bearing potential
16. A negative serum pregnancy test for females of child bearing potential or those <2 years after the onset of the menopause
17. Patients will have provided written informed consent
18. Target gender: male and female
19. Lower age limit 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 940; UK Sample Size: 940; Description: 940 patients with DLBCL

Participant exclusion criteria

1. 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.
2. Uncontrolled systemic infection
3. History of cardiac failure of uncontrolled angina
4. Clinical CNS involvement
5. Serological positivity for Hepatitis C, B or known HIV infection. Viral serological testing is not mandated for study entry, but considered standard of care. Patients who are HepBsAg positive will not be eligible.
6. Serious medical or psychiatric illness likely to affect participation or that may compromise the ability to give informed consent
7. 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
8. History of allergic reaction to substances containing boron or mannitol
9. Patient unwilling to abstain from green tea and preparations made from green tea as bortezomib may interact with these
10. Any co-existing medical or psychological condition that would compromise ability to give informed consent

Recruitment start date

13/04/2011

Recruitment end date

12/04/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Southampton Clinical Trials Unit
Southampton
SO16 6YD
United Kingdom

Sponsor information

Organisation

Southampton University Hospitals NHS Trust (UK)

Sponsor details

University of Southampton Clinical Trials Unit
MP131
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

Janssen-Cilag Ltd

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes