A Randomised Evaluation of Molecular Guided Therapy for Diffuse Large B-cell Lymphoma With Bortezomib
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 800 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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression Free Survival
Prof Peter Johnson
University Hospital Southampton NHS Foundation Trust.
United Kingdom: Medicines and Healthcare Products Regulatory Agency