Thalidomide-Dexamethasone (TD) is a standard induction therapy for Multiple Myeloma (MM). The present study is designed to compare TD with VELCADE-Thalidomide-Dexamethasone (VTD) as induction therapy in preparation for, and as consolidation after, melphalan-based double autologous stem cell transplantation for previously untreated patients aged ≤65 years with symptomatic MM. Primary study endpoint is the rate of complete response (CR) plus near-complete response (nCR) to induction treatment. Secondary endpoints include the rate of CR plus nCR to double transplantation and subsequent consolidation therapy, time to progression (TTP), progression-free survival (PFS),overall survival (OS) and toxicity profile of both VTD and TD.
Name: Velcade
Description: INDUCTION THERAPY: 1.3 mg/sqm as a bolus i.v. injection on days 1, 4, 8 and 11 (3 courses, 21 days each) REMISSION CONSOLIDATION THERAPY: 1.3 mg/sqm as a bolus i.v. injection on days 1, 8, 15 and 22 (2 courses, 35 days each)Type: DrugVTD
Name: Thalidomide
Description: INDUCTION THERAPY: 100 mg/d on days 1-14, 200 mg/d on days 15-63 (in case of delay of HD-CTX , Thalidomide will be continued until the day before Cyclophosphamide as priming therapy for PBSC collection) AFTER PBSC COLLECTION: 100 mg/d from day after last PBSC collection until the day before first course of MEL-200 AFTER FIRST TRANSPLANTATION: 100 mg/d from recovery of hematopoiesis until the day before the second course of MEL-200 REMISSION CONSOLIDATION THERAPY (starting 3 months after the second autologous transplantation): 100 mg/d days 1-70Type: DrugVTD TD
Name: Dexamethasone
Description: INDUCTION THERAPY VTD ARM: 40 mg/d days 1-2, 4-5, 8-9 and 11-12 (3 cycles, 21 days each) TD ARM: 40 mg/d days 1-4 and 9-12 (3 cycles, 21 days each) AFTER PBSC COLLECTION: 40 mg/d for 4 days (starting the same day of resumption of Thalidomide) AFTER FIRST TRANSPLANTATION: 40 mg/d for 4 days (starting the same day of resumption of Thalidomide) and repeated every 28 days, for 3 months REMISSION CONSOLIDATION THERAPY (starting 3 months after the second autologous transplantation) VTD ARM: 40 mg/d days 1-2, 8-9, 15-16 and 22-23 (2 cycles, 35 days each) TD ARM: 40 mg/d days 14 and 20-23 (2 cycles, 35 days each)Type: DrugVTD TD
Name: Peripheral Blood Stem Cell (PBSC) collection
Description: Cyclophosphamide (CTX): 4 g/sqm given in a single day (day 0) G-CSF: 10 µcg/kg/d, starting on day +2 from CTX and continuing until completion of PBSC collectionType: ProcedureVTD TD
Name: First Autologous Transplantation
Description: HIGH-DOSE MELPHALAN (MEL-200): 200 mg/sqm, given as a single dose i.v. (day -2) followed by PBSC infusion 48 hours later (day 0) G-CSF: 5 µcg/kg daily starting from day +6 after grafting and continuing until the patient's ANC is more than 0.5x10^9/L for 3 consecutive daysType: ProcedureVTD TD
Name: Second Autologous Transplantation
Description: HIGH-DOSE MELPHALAN (MEL-200): 200 mg/sqm, given as a single dose i.v. (day -2) followed by PBSC infusion 48 hours later (day 0) G-CSF: 5 µcg/kg daily starting from day +6 after grafting and continuing until the patient's ANC is more than 0.5x10^9/L for 3 consecutive daysType: ProcedureVTD TD
Description: Responses to induction therapy were reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the European Group for Blood and Marrow Transplantation (EBMT), with the addition of nCR (100% M-protein reduction by electrophoresis, but immunofixation-positive) and very good partial response (VGPR) (at least 90% serum and urine M-protein reduction) categories. Comparisons of response rates between treatment arms are performed using Fisher's exact test.
Measure: Rate of CR+nCR to induction treatment Time: 63 days after the start day of either TD or VTD as induction therapyDescription: Responses to autotransplantation(s) and consolidation therapy were reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the EBMT, with the addition of nCR and VGPR categories. Comparisons of response rates between treatment arms are performed using Fisher's exact test. Comparisons of response rates between treatment arms are performed using Fisher's exact test.
Measure: Rate of CR+nCR to autotransplantation(s) and subsequent consolidation therapy Time: 90 days after the second autologous transplantation and 70 days after the beginning of either TD or VTD as consolidation therapyDescription: TTP is defined as time from start of induction treatment with either TD or VTD to relapse or progression, as evaluated according to EBMT criteria. Comparison of TTP between treatment arms is performed using the log-rank test; distributions are estimated using Kaplan-Meier methodology.
Measure: Time To Progression (TTP) Time: Average time period between the start day of either TD or VTD as induction therapy and the day of relapse or progressionDescription: PFS is defined as time from start of treatment to progression/relapse, or death, whichever occurs firstly. Comparison of PFS between treatment arms is performed using the log-rank test; distributions are estimated using Kaplan-Meier methodology.
Measure: Progression-Free Survival (PFS) Time: Average time period between the start day of either TD or VTD as induction therapy and the day of relapse or progression or death, whichever occurs firstlyDescription: OS is defined as time from start of treatment to death. Comparison of OS between treatment arms is performed using the log-rank test; distributions are estimated using Kaplan-Meier methodology.
Measure: Overall Survival (OS) Time: Average time period between the start day of either TD or VTD as induction therapy and the day of death, due to any causeDescription: Safety is monitored until 30 days after the last dose of study drug. Toxicities are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Rates of adverse events are compared between treatment arms using the chi-square test.
Measure: Safety Time: Average time period between the start day of either TD or VTD as induction therapy and the day of any toxicity/adverse event(s) recorded during and after study drug administrationAllocation: Randomized
Parallel Assignment
There is one SNP
- Patient has a previous diagnosis of antiphospholipid antibodies or lupus anticoagulant, factor V Leiden mutation, prothrombin G21210A mutation, antithrombin, protein C or S deficiency. --- G21210A ---