VELCADE-Thalidomide-Dexamethasone (VTD) vs Thalidomide-Dexamethasone (TD) Incorporated Into Double Autotransplantation for Untreated Multiple Myeloma (MM)
- Conditions
- Multiple Myeloma
- Interventions
- Procedure: Peripheral Blood Stem Cell (PBSC) collectionProcedure: First Autologous TransplantationProcedure: Second Autologous Transplantation
- Registration Number
- NCT01134484
- Lead Sponsor
- Michele Cavo
- Brief Summary
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.
- Detailed Description
This prospective phase 3 trial is aimed at evaluating whether, in comparison with standard TD, addition of Velcade to TD increases rate of CR and nCR from 15% to 30%, respectively. For this purpose, symptomatic patients aged 18-65 years with previously untreated MM and quantifiable M-protein in serum or urine are randomized (1:1) to receive induction therapy comprising three 3-week cycles of Velcade 1.3 mg/sqm, days 1, 4, 8, 11, thalidomide 100 mg, days 1-14, cycle 1, then 200 mg daily, and dexamethasone 40 mg, days 1, 2, 4, 5, 8, 9, 11, 12, or thalidomide and dexamethasone (same schedule and dosage as in VTD). Randomization to VTD or TD is stratified according to International Staging System disease stage at diagnosis. Following induction therapy, patients in both arms receive cyclophosphamide (4 g/sqm, day 0 and granulocyte colony-stimulating factor, 10 μcg/kg/day, from day +2) to collect autologous peripheral blood stem cells (minimum threshold CD34+ cells: 4 x 10\^6/kg) and two subsequent courses of stem cell-supported high dose melphalan (200 mg/sqm), 3 to 6 months apart. Upon neutrophil (≥1 x 10\^9/L) and platelet (≥75 x 10\^9/L) recovery following the first autotransplantation, patients receive thalidomide (100 mg daily) and dexamethasone (40 mg, days 1-4 every 4 weeks) as bridge therapy until the day before the second transplantation.
Patients initially randomized to receive VTD or TD induction therapy are planned to receive two 5-week cycles of VTD (Velcade 1.3 mg/sqm, days 1, 8, 15, 22; thalidomide 100 mg daily; dexamethasone 40 mg, days 1, 2, 8, 9, 15, 16, 22, 23) or TD (thalidomide 100 mg daily; dexamethasone 40 mg, days 1-4 and 20-23) as consolidation therapy, starting 3 months after last transplant. Maintenance therapy comprise dexamethasone 40 mg, days 1-4, repeated monthly until relapse or progression.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 480
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description VTD Peripheral Blood Stem Cell (PBSC) collection - TD First Autologous Transplantation - VTD Velcade - VTD Second Autologous Transplantation - VTD First Autologous Transplantation - TD Peripheral Blood Stem Cell (PBSC) collection - TD Second Autologous Transplantation - VTD Thalidomide - VTD Dexamethasone - TD Dexamethasone - TD Thalidomide -
- Primary Outcome Measures
Name Time Method Rate of CR+nCR to induction treatment 63 days after the start day of either TD or VTD as induction therapy 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.
- Secondary Outcome Measures
Name Time Method Rate of CR+nCR to autotransplantation(s) and subsequent consolidation therapy 90 days after the second autologous transplantation and 70 days after the beginning of either TD or VTD as consolidation therapy 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.
Time To Progression (TTP) Average time period between the start day of either TD or VTD as induction therapy and the day of relapse or progression 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.
Progression-Free Survival (PFS) 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 firstly 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.
Overall Survival (OS) Average time period between the start day of either TD or VTD as induction therapy and the day of death, due to any cause 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.
Safety 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 administration 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.
Trial Locations
- Locations (1)
AOU di Bologna Policlinico S.Orsola-Malpighi, UO di Ematologia
🇮🇹Bologna, Italy