The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor.

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  • Additional Information
    • Affiliation:
      Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
      Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
      Centre for Haematology, Imperial College London, London, UK
      Division of Molecular Pathology, The Institute of Cancer Research, London, UK
      Centre for Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
      Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK
    • Corporate Authors:
    • Abstract:
      Background: Multiple myeloma is a plasma cell tumour with approximately 5500 new cases in the UK each year. Ixazomib is a next generation inhibitor of the 20S proteasome and is thought to be an effective treatment for those who have relapsed from bortezomib. The combination of cyclophosphamide and dexamethasone (CD) is a recognised treatment option for patients with relapsed refractory multiple myeloma (RRMM) who have relapsed after treatment with bortezomib and lenalidomide, whilst also often being combined with newer proteasome inhibitors. The most apparent combination for ixazomib is therefore with CD.Methods: MUK eight is a randomised, controlled, open, parallel group, multi-centre phase II trial that will recruit patients with RRMM who have relapsed after treatment with thalidomide, lenalidomide, and a proteasome inhibitor. The primary objective of the trial is to evaluate whether ixazomib in combination with cyclophosphamide and dexamethasone (ICD) has improved clinical activity compared to CD in terms of progression-free survival (PFS). Secondary objectives include comparing toxicity profiles and the activity and cost-effectiveness of both treatments. Since opening, the trial has been amended to allow all participants who experience disease progression (as per the IMWG criteria) on the CD arm to subsequently switch to receive ICD treatment, once progression has been confirmed with two clinical members of the Trial Management Group (TMG). This 'switch' phase of the study is exploratory and will assess second progression-free survival measured from randomisation to second disease progression (PFS2) and progression-free survival from the point of switching to second disease progression (PFS Switch) in participants who switch from CD to ICD treatment.Discussion: Development of ixazomib offers the opportunity to further investigate the value of proteasome inhibition through oral administration in the treatment of RRMM. Previous studies investigating the safety and efficacy of ICD in patients with RRMM demonstrate a toxicity profile consistent with ixazomib in combination with lenalidomide and dexamethasone, whilst the combination showed possible activity in RRMM patients. Further investigation of the anti-tumour effect of this drug in RRMM patients is therefore warranted, especially since no trials comparing CD with ICD have been completed at present.Trial Registration: ISRCTN number: ISRCTN58227268 . Registered on 26 August 2015.
    • Journal Subset:
      Biomedical; Europe; UK & Ireland
    • ISSN:
      1745-6215
    • MEDLINE Info:
      PMID: NLM33008427 NLM UID: 101263253
    • Publication Date:
      In Process
    • Publication Date:
      20201014
    • DOI:
      10.1186/s13063-020-04739-8
    • Accession Number:
      146197047
  • Citations
    • ABNT:
      HINSLEY, S. et al. The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor. Trials, [s. l.], v. 21, n. 1, p. 1–11, 2020. DOI 10.1186/s13063-020-04739-8. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=146197047. Acesso em: 1 dez. 2020.
    • AMA:
      Hinsley S, Walker K, Sherratt D, et al. The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor. Trials. 2020;21(1):1-11. doi:10.1186/s13063-020-04739-8
    • APA:
      Hinsley, S., Walker, K., Sherratt, D., Bailey, L., Reed, S., Flanagan, L., McKee, S., Brudenell Straw, F., Dawkins, B., Meads, D., Auner, H. W., Kaiser, M. F., Cook, M., Brown, S., & Cook, G. (2020). The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor. Trials, 21(1), 1–11. https://doi.org/10.1186/s13063-020-04739-8
    • Chicago/Turabian: Author-Date:
      Hinsley, Samantha, Katrina Walker, Debbie Sherratt, Lucy Bailey, Sadie Reed, Louise Flanagan, Sophie McKee, et al. 2020. “The MUK Eight Protocol: A Randomised Phase II Trial of Cyclophosphamide and Dexamethasone in Combination with Ixazomib, in Relapsed or Refractory Multiple Myeloma (RRMM) Patients Who Have Relapsed after Treatment with Thalidomide, Lenalidomide and a Proteasome Inhibitor.” Trials 21 (1): 1–11. doi:10.1186/s13063-020-04739-8.
    • Harvard:
      Hinsley, S. et al. (2020) ‘The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor’, Trials, 21(1), pp. 1–11. doi: 10.1186/s13063-020-04739-8.
    • Harvard: Australian:
      Hinsley, S, Walker, K, Sherratt, D, Bailey, L, Reed, S, Flanagan, L, McKee, S, Brudenell Straw, F, Dawkins, B, Meads, D, Auner, HW, Kaiser, MF, Cook, M, Brown, S & Cook, G 2020, ‘The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor’, Trials, vol. 21, no. 1, pp. 1–11, viewed 1 December 2020, .
    • MLA:
      Hinsley, Samantha, et al. “The MUK Eight Protocol: A Randomised Phase II Trial of Cyclophosphamide and Dexamethasone in Combination with Ixazomib, in Relapsed or Refractory Multiple Myeloma (RRMM) Patients Who Have Relapsed after Treatment with Thalidomide, Lenalidomide and a Proteasome Inhibitor.” Trials, vol. 21, no. 1, Oct. 2020, pp. 1–11. EBSCOhost, doi:10.1186/s13063-020-04739-8.
    • Chicago/Turabian: Humanities:
      Hinsley, Samantha, Katrina Walker, Debbie Sherratt, Lucy Bailey, Sadie Reed, Louise Flanagan, Sophie McKee, et al. “The MUK Eight Protocol: A Randomised Phase II Trial of Cyclophosphamide and Dexamethasone in Combination with Ixazomib, in Relapsed or Refractory Multiple Myeloma (RRMM) Patients Who Have Relapsed after Treatment with Thalidomide, Lenalidomide and a Proteasome Inhibitor.” Trials 21, no. 1 (October 2, 2020): 1–11. doi:10.1186/s13063-020-04739-8.
    • Vancouver/ICMJE:
      Hinsley S, Walker K, Sherratt D, Bailey L, Reed S, Flanagan L, et al. The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor. Trials [Internet]. 2020 Oct 2 [cited 2020 Dec 1];21(1):1–11. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=146197047