Vorinostat, Bortezomib and Dexamethasone in Multiple Myeloma (MUKfour)
Bortezomib is an established treatment in multiple myeloma; it is common practice in the UK to administer bortezomib with dexamethasone. This practice is based on data that supports improved response rates with this combination.
Recent trial data indicates that the addition of vorinostat to bortezomib treatment overcomes treatment resistance to bortezomib. As such this current trial is designed to investigate the efficacy, safety and tolerability of combination treatment with vorinostat, bortezomib and dexamethasone in patients with relapsed and relapsed refractory myeloma.
A comparison of this Phase II trial with the pivotal Phase III trial conducted by MSD (using the labelled bortezomib indication without dexamethasone) will address the impact of dexamethasone in regards to tolerability and additional efficacy in myeloma patients.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Combination Treatment With Vorinostat, Bortezomib and Dexamethasone in Patients With Relapsed and Relapsed Refractory Multiple Myeloma|
- Overall response rate to vorinostat, bortezomib and dexamethasone. [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]To assess the number and proportion of participants with at least a partial response (PR) or better within 8 cycles of protocol treatment with vorinostat, bortezomib and dexamethasone.
- Number of dose reductions during treatment with vorinostat, bortezomib and dexamethasone. [ Time Frame: up to 24 weeks ] [ Designated as safety issue: Yes ]To assess the dose reduction profile of combination treatment with vorinostat, bortezomib and dexamethasone. The proportion of participants experiencing a dose reduction or terminating treatment early due to toxicity will be assessed.
- Overall numbers and rates of adverse events [ Time Frame: Up to 18 months ] [ Designated as safety issue: Yes ]Safety and toxicity analyses will summarise the overall serious adverse event and adverse events rates including the number and proportion of participants with at least one safety event. SAEs will be additionally presented by the relationship to study treatment, seriousness criteria, event outcome, duration and by MedDRA body system coding.
- Progression free survival [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]A progression-free survival curve will be calculated using the Kaplan Meier method and median PFS estimates will be presented
- Maximum response to treatment [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]The overall number and proportion of participants in each response category within 8 cycles of treatment and overall across all treatment including the maintenance phase
- Time to maximum response [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]The time to maximum response will be calculated from the date of registration to the date of maximum response. Participant's who progress and do not achieve a maximum response will be censored at the time of progression. Median time to maximum response will be presented.
- Matched pairs analysis [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]A matched pairs analysis will be carried out looking at overall response, PFS, dose reductions and toxicity in participants treated with vorinostat in combination with bortezomib and dexamethasone (VVD) in this current study compared to participants randomised to the bortezomib/vorinostat (VV) arm in the pivotal MSD phase III study.
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||March 2017|
|Estimated Primary Completion Date:||March 2017 (Final data collection date for primary outcome measure)|
Experimental: Vorinostat Velcade Dexamethasone (VVD)
Up to 8 cycles of VVD followed by vorinostat maintenance until disease progression.
Cycles 1-8 (21-day cycle)
Drug: Vorinostat Velcade Dexamethasone
Other Name: Bortezomib (velcade)
|Contact: Louise M Flanagan, BSc PhD||+44 113 343 email@example.com|
|Nottingham University Hospital|
|Nottingham, Nottinghamshire, United Kingdom, NG5 1PB|
|Royal Marsden NHS Foundation Trust|
|London, United Kingdom, SM2 5PT|
|Principal Investigator:||Faith Davies, MRCPath||Institute of Cancer Research, United Kingdom|