title: The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma.
abstract: BACKGROUND
  Multiple myeloma is a plasma cell tumour with an annual incidence in the UK of approximately 40-50 per million i.e. about 4500 new cases per annum. The triple combination cyclophosphamide, bortezomib (Velcade®) and dexamethasone (CVD) is an effective regimen at relapse and has emerged in recent years as the standard therapy at first relapse in the UK. Carfilzomib has good activity as a single agent in the relapsed setting, and it is expected that efficacy will be improved when used in combination with dexamethasone and cyclophosphamide.
  
  
  METHODS
  MUK Five is a phase II open label, randomised, controlled, parallel group, multi-centre trial that will compare the activity of carfilzomib, cyclophosphamide and dexamethasone (CCD) with that of CVD, given over an equivalent treatment period (24 weeks), in participants with multiple myeloma at first relapse, or refractory to no more than 1 line of treatment. In addition, the study also aims to assess the utility of a maintenance schedule of carfilzomib in these participants. The primary objective of the trial is to assess whether CCD provides non-inferior activity in terms of ≥ VGPR rates at 24 weeks, and whether the addition of maintenance treatment with carfilzomib to CCD provides superior activity in terms of progression-free survival, as compared to CCD with no maintenance. Secondary objectives include comparing toxicity profiles, further summarizing and comparing the activity of the different treatment arms and analysis of the effect of each treatment arm on minimal residual disease status.
  
  
  CONCLUSIONS
  The development of carfilzomib offers the opportunity to further explore the anti-tumour efficacy of proteasome inhibition and, based on the available evidence, it is important and timely to obtain data on the activity, toxicity and tolerability of this drug. In contrast to ongoing phase III trials, this phase II trial has a unique subset of participants diagnosed with multiple myeloma at first relapse or refractory to no more than 1 line of treatment and will also evaluate the utility of maintenance with carfilzomib for up to 18 months and investigate minimal residual disease status to provide information on depth of response and the prognostic impact thereof.
  
  
  BACKGROUND
  The trial is registered under ISRCTN17354232, December 2012.
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Brown
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Hinsley
authors.affiliation: Methodology of Biomedical Research and Public Health Programme, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Ballesteros
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Sue
authors.initials: S
authors.lastname: Bourne
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: McGarry
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Debbie
authors.initials: D
authors.lastname: Sherratt
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Flanagan
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: Walter
authors.initials: W
authors.lastname: Gregory
authors.affiliation: Department of Haematology, St Bartholomew's Hospital, London, UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Cavenagh
authors.affiliation: HMDS Laboratory, St James's University Hospital, Leeds, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Owen
authors.affiliation: Centre for Clinical Haematology, Nottingham University Hospitals, Nottingham, UK.
authors.forename: Cathy
authors.initials: C
authors.lastname: Williams
authors.affiliation: The Institute of Cancer Research, Sutton, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Myeloma UK, Edinburgh, UK.
authors.forename: Eric
authors.initials: E
authors.lastname: Low
authors.affiliation: UCL Cancer Institute, 72 Huntley Street, WC1E 6BT London, UK.
authors.forename: Kwee
authors.initials: K
authors.lastname: Yong
keywords: Carfilzomib; First relapse multiple myeloma; Phase II; Primary refractory multiple myeloma