Know Cancer

forgot password

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

Phase 3
18 Years
Open (Enrolling)
Lymphoma, Large B-Cell, Diffuse

Thank you

Trial Information

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.

Inclusion Criteria:

- 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.

- 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. REMoDL-B Protocol
Version 2.0 6th January 2011.

- 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.

Exclusion Criteria:

- 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.

- 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. Patients
who are HepBsAg positive 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.

- Any co-existing medical or psychological condition that would compromise ability to
give informed consent.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Prof Peter Johnson

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospital Southampton NHS Foundation Trust.


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

April 2011

Completion Date:

April 2020

Related Keywords:

  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Large B-Cell, Diffuse
  • Bortezomib
  • R-CHOP
  • Molecular profiling
  • Chemotherapy
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse