A Phase 3, Prospective, Randomized Clinical Study of VELCADE-Thalidomide-Dexamethasone (VTD) Versus Thalidomide-Dexamethasone (TD) for Previously Untreated Multiple Myeloma (MM) Patients Who Are Candidates to Receive Double Autologous Transplantation
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.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Rate of CR+nCR to induction treatment
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.
63 days after the start day of either TD or VTD as induction therapy
No
Michele Cavo, MD
Principal Investigator
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
Italy: Ethics Committee
MM-BO2005
NCT01134484
May 2006
December 2015
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