REMoDL-B v1.0

• Research type

  Research Study

• Full title

  A randomised evaluation of molecular guided therapy for diffuse large B-cell lymphoma with Bortezomib

• IRAS ID

  61884

• Contact name

  Peter Johnson

• Sponsor organisation

  University Hospital Southampton NHS Foundation Trust

• Eudract number

  2010-022422-32

• ISRCTN Number

  n/a

• Research summary

  Research Summary

  This study of treatment for diffuse large B-cell lymphoma aims to determine whether adding bortezomib to standard combination chemotherapy and rituximab (R-CHOP) 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 sub-group of patients might benefit more from the addition of bortezomib. Patients will be randomised to one of two groups (RB-CHOP or R-CHOP) on the basis of their molecular subgroup.

  Summary of Results

  MAIN FINDINGS REMoDL-B was a study to see if adding the drug bortezomib to standard treatment (known as R-CHOP) would benefit patients with diffuse large B-cell lymphoma.

  We found that for most participants, adding bortezomib did not make a difference to whether or not their lymphoma was likely to come back.
  Participants who received bortezomib were slightly more likely to report peripheral neuropathy (reduced feeling in hands and feet), but otherwise people did not experience more problems when taking the extra drug. Almost 90% of participants completed all 6 cycles of treatment.

  However, as an unexpected outcome of the trial we have identified a small group of patients whose lymphoma was worse than others and who may benefit from other types of treatment in the future. That type of lymphoma is called molecular high-grade (MHG) lymphoma.

  It is also possible that patients with MHG and also those with activated B-cell (ABC) lymphoma have benefitted from the bortezomib, and we are still analysing results in more detail. The outcomes will be published next year.

  Those are the main findings, but if you wish to read a more detailed account of this analysis, the results have been published in a scientific journal, The Lancet Oncology, Vol. 20, No. 5, p649–662

  A further scientific paper detailing the new MHG group has been published here, Journal of Clinical Oncology, 2019 Jan 20;37(3):202-212.

  WHAT WAS THE PURPOSE OF THE STUDY?
  The aim of REMoDL-B was to find out if adding bortezomib to standard therapy (a drug combination called R-CHOP) would provide clinical benefit to those with large B-cell lymphoma. The name REMoDL-B is a summary of the scientific description - A Randomised Evaluation of Molecular Guided Therapy for Diffuse Large B-cell Lymphoma with Bortezomib.

  WHO VOLUNTEERED TO TAKE PART?
  1129 patients with diffuse large B-cell lymphoma volunteered to participate in the REMoDL-B trial, in the UK and in Switzerland, from June 2011 until June 2015.

  HOW DID WE DELIVER THE STUDY?
  For the first cycle of treatment, we gave all patients the standard therapy, which is R-CHOP chemotherapy. Then a computer randomised participants to one of two arms; R-CHOP alone (the control arm) or RB-CHOP, ie R-CHOP with bortezomib (the intervention arm). Participants stayed on their arm for the five remaining cycles of treatment.

  At the start of treatment, we analysed patients’ lymphoma biopsies to establish which subtype of diffuse large B-cell lymphoma was present. This information allowed us to ensure there were balanced number of subtypes in each treatment arm after randomisation. The subtypes we identified were either Activated B-Cell (ABC), Germinal Centre B-cell (GCB) or Unclassified (Unc). If you wish to find out what subtype you had please contact your trial team.

• REC name

  South Central - Hampshire B Research Ethics Committee

• REC reference

  10/H0504/79

• Date of REC Opinion

  7 Dec 2010

• REC opinion

  Favourable Opinion