DEFENCE

• Research type

  Research Study

• Full title

  Denosumab for high risk SMM and SLiM CRAB positive, early myeloma patient- a randomised, placebo controlled, phase II trial.

• IRAS ID

  255494

• Contact name

  Karthik Ramasamy

• Contact email

  karthik.ramasamy@ouh.nhs.uk

• Sponsor organisation

  Arbeitsgemeinschaft medikamentöse Tumortherapie gemeinnützige GmbH

• Eudract number

  2018-000924-32

• Clinicaltrials.gov Identifier

  NCT03792763

• Duration of Study in the UK

  6 years, 6 months, 0 days

• Research summary

  Previous research led to the identification of risk factors for the transformation of patients with smouldering multiple myeloma (SMM) into active multiple myeloma. Patients with high risk SMM transform with a median of two years into active myeloma. A recent consensus of international myeloma experts defined a new group of patients with ‘early myeloma’. Those patients present with one of the newly established ‘SLiM CRAB’ criteria, BMPC (bone marrow plasma cells) ≥60%, or FLC (free light chain) ratio ≥100, and or >1 MRI detected focal lesion. Their risk for developing active, CRAB positive myeloma with 2 years varies between 64% and 95%. Denosumab a fully human monoclonal antibody that binds to and neutralises RANKL, has been shown to reduce the rates of skeletal-related events (SRE). It is currently approved for the prevention of SRE in adults with advanced malignancies involving bone and to treat patient with multiple myeloma.
  This is a randomised controlled phase II trial which aims to evaluate whether the reported benefits of denosumab, delay of SRE and decrease in myeloma growth promotion, reduce the risk of progression of high-risk SMM and of early ‘SLiM CRAB’ myeloma into active CRAB positive myeloma. Approximately 50 patients with high risk SMM or SLiM CRAB are expected to be recruited from 7 sites within the UK over 2.5 years. Patients consenting to enter the trial will undergo a number of investigations during the screening process to assess their eligibility for the trial. Eligible patients will be randomised to receive treatment with either Denosumab or placebo every 4 weeks for 6 months, then every 3 months for a total of 3 years or until progression to active MM. The study duration for each patient will be a maximum of 36 months treatment plus a minimum of 12 months of follow up.
  

• REC name

  South Central - Oxford B Research Ethics Committee

• REC reference

  20/SC/0267

• Date of REC Opinion

  23 Sep 2020

• REC opinion

  Further Information Favourable Opinion