Velcade (bortezomib), thalidomide and dexamethasone (VTD) has been demonstrated to be a highly effective combination in both patients with previously untreated and those with relapsed multiple myeloma. In previously untreated patients VTD demonstrated clear superiority to TD as induction therapy prior to planned tandem autologous stem cell transplant. The rationale of this trial is to combine a 'gold standard' antiMM combination with the HDAC inhibitor Panobinostat. There is emerging data to support the concept of clinical synergy between BTZ and HDACi's. The purpose of this study is to determine the maximum tolerated dose (MTD) and estimated response rates of panobinostat, administered in combination with VTD, in subjects with relapsed and relapsed/refractory multiple myeloma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Birmingham Heartlands Hospital
Birmingham, UK, United Kingdom
Royal Liverpool University Hospital
Liverpool, United Kingdom
St Bartholomew's Hospital
London, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
Guy's Hospital
London, United Kingdom
Dose limiting toxicities (DLTs)
The number of participants experiencing DLTs within the first cycle of VTD-pano will be presented, with descriptive summaries of the specific DLTs observed. Summaries will be presented for each dose level.
Time frame: From cycle 1 day 1 up to the administration of cycle 2 day 1 (up to 22 days)
Proportion o f participants achieving at least partial response
The proportion of participants achieving at least a partial response within 16 cycles of VTD-pano will be presented, with corresponding 80% and 95% confidence intervals
Time frame: within 16 cycles of therapy (an expected average of 48 weeks)
Safety and toxicity
The proportion of participants experiencing DLTs and other toxicities, overall and by cycle as graded by CTCAE V4.0.
Time frame: Throughout the trial, expected to be 3 years
Proportion of patients with each maximum response category
The number and proportion of participants in each response category within 16 cycles of VTD-pano will be presented with corresponding 95% confidence intervals.
Time frame: within 16 cycles of therapy (an expected average of 48 weeks)
Time to maximum response to therapy
Time to maximum response is defined as the time from registration until the patient achieves any of the categories CR, VGPR, PR, MR or SD as their maximum response. Median time to maximum response will be presented.
Time frame: from registration until the participant achieves any of the categories CR, VGPR, PR, MR or SD as their maximum response (up to 100 weeks - 48 weeks of treatment plus 52 weeks maintenance)
Progression free survival
A progression-free survival curve will be calculated using the Kaplan Meier method and median PFS estimates will be presented.
Time frame: from registration to first documented evidence of disease progression or death (up to 100 weeks)
Compliance to therapy
Compliance to therapy will be summarised descriptively, including number of doses missed and number of dose reductions throughout the treatment period.
Time frame: from initial treatment received as per protocol until treatment withdrawal (up to 100 weeks)
Feasibility of panobinostat maintenance
The duration of maintenance and reasons for stopping will be summarised
Time frame: up to 12 months
Overall survival
Overall survival (OS) curves will be calculated using the Kaplan Meier method. Median OS, and OS estimates at 12 months, will be presented, if appropriate.
Time frame: from registration to date of death
The proportion of participants mobilising sufficient stem cells for transplant(out of those undergoing mobilisation)
To be determined by the satisfactory collection of sufficient numbers of stem cells to support high-dose chemotherapy.
Time frame: up to 16 cycles of therapy (an expected average of 48 weeks)
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