The purpose of this study is to compare the effectiveness of bortezomib versus thalidomide in reducing free light chains in the blood of myeloma patients. In addition participants will receive bendamustine (chemotherapy) and dexamethasone (steroids), which increase the effectiveness of both bortezomib and thalidomide. The trial will also study whether an earlier reduction of free light chains increases the chances of the kidneys recovering.
Renal impairment is a life threatening condition of myeloma. 20-25% of patients will present at diagnosis with renal dysfunction. Outcome is poor due to high early mortality, with 28% of newly diagnosed myeloma patients in myeloma trials with renal failure not surviving beyond 100 days, compared with 10% overall. This study aims to establish: 1. Whether proteosomal inhibition (bortezomib) or immunomodulatory (thalidomide) based therapy achieves threshold reduction of serum free light chains (sFLCs) in a significant majority of patients. 2. Whether sFLC response to the first 2 cycles (early responder) predicts haematological and renal response to the next 2 cycles of therapy. 3. An early time point for assessment of sFLC reduction as a biomarker for response. Participants will be stratified by age and chronic kidney disease (CKD) stage to receive either bortezomib, bendamustine and dexamethasone (BBD) or thalidomide, bendamustine and dexamethasone (BTD).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
31
1.3 mg/m2 subcutaneously\* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). \*intravenous infusion available in case of patient intolerance to subcutaneous bortezomib
100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised)
60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised)
Basingstoke & North Hampshire Hospital
Basingstoke, United Kingdom
Heartlands Hospitals
Birmingham, United Kingdom
Kent & Canterbury Hospital
Canterbury, United Kingdom
St Helier Hospital
Epsom, United Kingdom
Number of Participants With >50% Reduction From Baseline in Serum Free Light Chain
Time frame: End of week 6 (after receiving two cycles of therapy)
Number of Participants With Different Renal Responses to Treatment
Time frame: End of week 12 (after receiving 4 cycles of therapy)
Haematological and Non-haematological Toxicity in Both Treatment Arms
Time frame: End of weeks 3, 6, 9, 12 (after receiving 4 cycles of therapy), 30 days after final treatment and 12 months after randomisation
Overall Survival
Time frame: 1 month post end of treatment and 1 year post randomisation
Renal Response After Two Cycles of Trial Treatment
Time frame: End of 2nd treatment cycle, week 6
Quality of Life Measured by the EQ-5D-3L Questionnaire at Baseline and 1 Month Follow up
The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is scored on a scale of 1 to 3: 1 (no problems), 2 (some problems), and 3 (extreme problems). Higher score equates to a worse outcome. As stated in the official EQ-5D user guide, patient responses to the 5 questions were converted into a single index value as per Dolan P (1997). Modeling valuations for EuroQol health states. Med Care 35(11):1095-108. These index values, with country specific value sets, facilitate the calculation of quality-adjusted life years (QALYs) that are used to inform economic evaluations of health care interventions. In the UK, the values range from -0.594 to +1.
Time frame: Baseline and 1 month follow up
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40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle
Royal Liverpool Hospital
Liverpool, United Kingdom
Kings College Hospital
London, United Kingdom
Churchill Hospital
Oxford, United Kingdom
Queen Alexandra Hospital
Portsmouth, United Kingdom
Great Western Hospital
Swindon, United Kingdom