MMVAR - Velcade: Study of Velcade for the Treatment of Myeloma Patients After Autologous Transplantation
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT00256776
- Brief Summary
This is an international study in adult patients diagnosed with multiple myeloma who have already received at least one autologous stem cell transplantation and who have responded but later progressed, or relapsed, at least one year after transplantation.
Eligible patients will be randomly assigned to one of two treatments: either Velcade plus Thalidomide plus Dexamethasone or Thalidomide plus Dexamethasone.
Thalidomide and Velcade are two new agents that have recently become available for the treatment of multiple myeloma, especially in relapsed patients. This study therefore aims to test the hypothesis that the combination treatment with Velcade plus Thalidomide plus Dexamethasone will result in a longer time to progression (measure of time after the disease is treated until it starts to get worse) than Thalidomide plus Dexamethasone alone.
- Detailed Description
Primary Objectives:
\* Test the hypothesis that treatment with Velcade plus Thalidomide plus Dexamethasone in combination, will result in a longer time to progression (TTP) than Thalidomide plus Dexamethasone in subjects with relapsed or progressive myeloma after autologous transplantation.
Secondary Objectives:
\* Compare the treatment groups for: overall survival; response rate (complete \& partial \& minimal) using standard criteria and treatment related complications.
Study design and methodology:
This is a prospective, randomized, parallel-group, open-label phase III, on an intention to treat, multicenter study. The main endpoint is time-to-failure (TTP=time to progression). The power is based on an initial assumption of a median TTP of 1.5 years in the experimental (Velcade) group and 1 year in the control group. The design of the study is group sequential. There will be 4 interim analyses and one final analysis. The study is designed to have a priori 90% power to detect the clinically relevant difference at completion of the study at 0.025 level. Patients with multiple myeloma whose disease has either progressed or relapsed at least one year after one or two autologous transplantations will be enrolled. Prior to random assignment, subjects will be stratified on center and number of autologous transplants.Subjects will be randomly assigned to treatment in a 1: 1 allocation within each stratum to Velcade plus Thalidomide plus Dexamethasone (VTD) or Thalidomide plus Dexamethasone. Velcade 1.3 mg/m2 will be given as an i.v. bolus on Days 1, 4, 8 and 11 followed by a 10-day rest period (Days 12 to 21) for 8 cycles (6 months) and then on Days 1, 8, 15, and 22 followed by a 20-day rest period (Days 23 to 42) for 4 cycles (6 months). In both arms, Thalidomide will be given at 200 mg/day per os for one year and Dexamethasone 40 mg/day per os four days every three weeks for one year.Treatment will continue until disease progression, or the occurrence of unacceptable treatment-related toxicity, or up to a total of 12 cycles of Velcade except for those subjects who have a continuing decrease in the levels of paraprotein after 12 cycles. These subjects may continue for as long as treatment is tolerated, and they continue to respond. If a subject has a CR, then treatment should continue at least 2 cycles after the objective response is confirmed. For subjects with a PR or stable disease, treatment may continue after a maximum objective response is confirmed unless the subject experiences unacceptable treatment-related toxicity or the subject has completed 12 cycles of treatment. Disease assessment will occur at the start of each cycle. If a subject discontinues treatment without disease progression, disease assessment will be performed every 3 weeks for 48-weeks from the start of the first dose of study entry drug. Subjects who have not progressed at the end of 48-week follow up period will be assessed every 6 weeks until disease progression is documented
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 269
- Male or female ≥18 years-of-age
- Multiple myeloma with evaluable disease
- Relapsing or having a progressive disease
- Karnofsky performance status > 50 %
- Life expectancy of at least 3 months
- Female of child-bearing potential must have a method of birth control and a negative serum or urine beta--human chorionic gonadotropin (β-HCG) pregnancy test at screening and all through the study
- Male must use contraception
- Voluntary written informed consent
- Non-secretory multiple myeloma
- Platelet count < 40,000 X 10^9/L
- Absolute neutrophil count <1.0 X 10^9/L
- Creatinine clearance <30 mL/minute
- Peripheral neuropathy >= Grade 2
- Seropositive for HIV, or active hepatitis A, B or C infection
- Pregnant or breastfeeding female
- Patient has hypersensitivity to bortezomib, boron or mannitol
- Other investigational drugs
- Serious medical or psychiatric illness
- Previous or concurrent malignancies at other sites
- Poorly controlled hypertension, uncontrolled or severe cardiovascular disease or uncontrolled diabetes mellitus
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Thal + Dex + Velcade Velcade (Bortezomib) - Thal + Dex + Velcade Thalidomide - Thal + Dex + Velcade Dexamethasone - Thal + Dex Thalidomide Standard treatment Thal + Dex Dexamethasone Standard treatment
- Primary Outcome Measures
Name Time Method Median Time to Progression (TTP) 3 year
- Secondary Outcome Measures
Name Time Method Progression Free Survival 3 year Overall Survival (Interval Between Date of Randomization and Death From Any Cause 1 year Response Rate (Proportion of Subjects Who Achieve Complete, Partial, or Minimal Response) 1 year
Trial Locations
- Locations (73)
Saint Joseph
🇧🇪Gilly, Belgium
Stadtdpital Triemli
🇨🇭Zurich, Switzerland
Medizinische Universitaet Wien
🇦🇹Vienna, Austria
Kantonsspital
🇨🇭Basel, Switzerland
Inselspital
🇨🇭Bern, Switzerland
UniversitatsSpital
🇨🇭Zurich, Switzerland
Edouard Herriot
🇫🇷Lyon, France
CHU Amiens
🇫🇷Amiens, France
Universitatsklinik
🇦🇹Innsbruck, Austria
UCL Mont-Godinne
🇧🇪Yvoir, Belgium
CHU Angers
🇫🇷Angers, France
Hospitalier de Dunkerque
🇫🇷Dunkerque, France
Hopital Michallon
🇫🇷Grenoble, France
Centre Hospitalier du Havre
🇫🇷Le Havre, France
CHRU de Lille
🇫🇷Lille, France
Centre Hospitalier de Mulhouse
🇫🇷Mulhouse, France
CHU Nancy
🇫🇷Nancy, France
Pierre Benite
🇫🇷Lyon, France
Hopital Cochin
🇫🇷Paris, France
Archet
🇫🇷Nice, France
Ospedale SS. Antonio e Biagio e Cesare Arrigo
🇮🇹Alessandria, Italy
Sheba MC
🇮🇱Tel Hashomer, Israel
Ospedale Riuniti
🇮🇹Bergamo, Italy
IOSI, Ospedale Civico
🇨🇭Bellinzona, Switzerland
CHUV
🇨🇭Lausanne, Switzerland
LA Onkologie/Medizin
🇨🇭Thun, Switzerland
University of Debrecen
🇭🇺Debrecen, Hungary
Kantonsspital Aarau
🇨🇭Aarau, Switzerland
Azienda Ospedale BMM
🇮🇹Reggio di Calabria, Italy
Addenbrookes
🇬🇧Cambridge, United Kingdom
A.O.S. Andrea
🇮🇹Rome, Italy
Hopital Cantonal Universitaire
🇨🇭Geneva, Switzerland
Great Western Hospital
🇬🇧Swindon, United Kingdom
St Joseph
🇧🇪Arlon, Belgium
Karl-Franzens
🇦🇹Graz, Austria
Wilhelminenspital
🇦🇹Vienna, Austria
RHMS
🇧🇪Baudour, Belgium
AZ St Jan
🇧🇪Brugge, Belgium
Bordet
🇧🇪Brussels, Belgium
University Hospital
🇩🇪Hamburg, Germany
Saint Luc
🇧🇪Brussels, Belgium
CH Jolimont
🇧🇪Haine-Saint-Paul, Belgium
Faculty Hospital
🇨🇿Olomouc, Czechia
Centre Hospitalier d'Antibes
🇫🇷Antibes, France
CHU Jean Minjoz
🇫🇷Besancon, France
Avicenne
🇫🇷Bobigny, France
Polyclinique Bordeaux Nord
🇫🇷Bordeaux, France
Morvan CHU
🇫🇷Brest, France
Hotel Dieu
🇫🇷Paris, France
ARC CHU Dijon
🇫🇷Dijon, France
Hopital Jean Bernard
🇫🇷Poitiers, France
Saint Antoine
🇫🇷Paris, France
CHU Hopital Sud
🇫🇷Rennes, France
Robert Debre
🇫🇷Reims, France
University of Cologne
🇩🇪Cologne, Germany
Medizinische Hochschule
🇩🇪Hannover, Germany
Universitatsklinikum Schleswig-Hostein
🇩🇪Lubeck, Germany
Medizinische und Poliklinik II
🇩🇪Wurzburg, Germany
AO Spedali Civili di Brescia
🇮🇹Brescia, Italy
Federico II
🇮🇹Naples, Italy
V. Cervello
🇮🇹Palermo, Italy
Ospedale Maggiore
🇮🇹Milan, Italy
Kantonsspital Baden
🇨🇭Baden, Switzerland
Henri Becquerel
🇫🇷Rouen, France
CHRU Tours
🇫🇷Tours, France
DKD Wiesbaden
🇩🇪Wiesbaden, Germany
Uniklinik Leipzig
🇩🇪Leipzig, Germany
Klinikum Bremen
🇩🇪Bremen, Germany
St Laszlo Hospital
🇭🇺Budapest, Hungary
Rambam MC
🇮🇱Haifa, Israel
Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Erasme CHU
🇧🇪Brussels, Belgium
Clinique Saint-Pierre
🇧🇪Ottignies, Belgium