The primary objective is to compare the time to progression (TTP) of three daily doses of thalidomide (100, 200 and 400 mg) with high-dose dexamethasone in relapsed refractory multiple myeloma (MM) patients and to subsequently select the optimum thalidomide dose in terms of median TPP and toxicity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
499
Oral thalidomide (100mg or 200mg or 400 mg/day) administered to the patient once daily until progression of the disease and for a maximum of 336 + 36 days (12 cycles of 28 +/- 3 days).
High dose oral dexamethasone will be administered at a dose of 40mg/day on days 1-4, 9-12 and 17-20 of each 28-day cycle for cycles 1-4. Beginning with cycle 5, the oral dexamethasone dosing schedule will be reduced to 40mg/day on days 1-4 of each 28-day cycle. Dexamethasone will be administered until progression of the disease and for a maximum of 336 +/- 36 days (12 cycles of 28 +/- 3 days).
The evaluation of Independent Review Committee-documented time to progression (TTP).
Time frame: >160 "IRC confirmed" disease progression in the Dexamethasone or Thalidomide 400 mg/day arms
Response rate (CR + PR), according to the EBMT criteria
Time frame: Every 4 weeks
Response duration
Time frame: Every 4 weeks
Clinical benefit as measured by ECOG performance status, transfusion requirement and Grade ≥3 infections (assessed by the National Cancer Institute Common Toxicity Criteria)
Time frame: Every 4 weeks
Progression-free survival (PFS)
Time frame: Disease progression evaluated every 4 weeks
Overall survival (OS)
Time frame: Evaluated after 150 deaths occurring in Dexamethasone and Thalidomide 400 mg arms
Composite of disease progression and death (recurrent time(s) from randomisation to disease progression and/or death)
Time frame: Evaluated after 160 "IRC confirmed" disease progression in the Dexamethasone or Thalidomide 400 mg/day arms
Quality of life as determined by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)
Time frame: Baseline/Week 8/ Week 16/Week 24/Week 32/Week 40/Week 48
Adverse events (AEs)
Time frame: Every 4 weeks
Assessment of peripheral neuropathy
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Time frame: Screening, Week 24, Week 48
Vital signs and physical examination
Time frame: Every 4 weeks
Clinical laboratory tests
Time frame: Every 4 weeks