Clinical trial NCT00256776: MMVAR - Velcade: Study of Velcade for the Treatment of Myeloma Patients After Autologous Transplantation
Official title: A Randomized Controlled Study of Velcade (Bortezomib) Plus Thalidomide Plus Dexamethasone Compared to Thalidomide Plus Dexamethasone for the Treatment of Myeloma Patients Progressing or Relapsing After Autologous Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Velcade
Autologous transplantation
Relapse
Disease progress
Lead sponsor: European Society for Blood and Marrow Transplantation
Sponsor class: NETWORK
Collaborators: name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Celgene Corporation
First posted: 2005-11-22
Enrollment: 269
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Median Time to Progression (TTP)
timeFrame: 3 year
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 3 year
measure: Overall Survival (Interval Between Date of Randomization and Death From Any Cause
timeFrame: 1 year
measure: Response Rate (Proportion of Subjects Who Achieve Complete, Partial, or Minimal Response)
timeFrame: 1 year
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Karl-Franzens
city: Innsbruck
country: Austria
facility: Universitatsklinik
city: Vienna
country: Austria
facility: Medizinische Universitaet Wien
city: Vienna
country: Austria
facility: Wilhelminenspital
city: Arlon
country: Belgium
facility: St Joseph
city: Baudour
country: Belgium
facility: RHMS
city: Brugge
country: Belgium
facility: AZ St Jan
city: Brussels
country: Belgium
facility: Bordet
city: Brussels
country: Belgium
facility: Erasme CHU
city: Brussels
country: Belgium
facility: Saint Luc
city: Brussels
country: Belgium
facility: University Hospital
city: Gilly
country: Belgium
facility: Saint Joseph
city: Haine-Saint-Paul
country: Belgium
facility: CH Jolimont
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre
city: Yvoir
country: Belgium
facility: UCL Mont-Godinne
city: Brno
country: Czechia
facility: University Hospital
city: Olomouc
country: Czechia
facility: Faculty Hospital
city: Amiens
country: France
facility: CHU Amiens
city: Angers
country: France
facility: CHU Angers
city: Antibes
country: France
facility: Centre Hospitalier d'Antibes
city: Besancon
country: France
facility: CHU Jean Minjoz
city: Bobigny
country: France
facility: Avicenne
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord
city: Brest
country: France
facility: Morvan CHU
city: Clermont-Ferrand
country: France
facility: Hotel Dieu
city: Dijon
country: France
facility: ARC CHU Dijon
city: Dunkerque
country: France
facility: Hospitalier de Dunkerque
city: Grenoble
country: France
facility: Hopital Michallon
city: La Roche sur Yon
country: France
city: Le Havre
country: France
facility: Centre Hospitalier du Havre
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Edouard Herriot
city: Lyon
country: France
facility: Pierre Benite
city: Metz
country: France
city: Mulhouse
country: France
facility: Centre Hospitalier de Mulhouse
city: Nancy
country: France
facility: CHU Nancy
city: Nantes
country: France
facility: Hotel Dieu
city: Nice
country: France
facility: Archet
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hotel Dieu
city: Paris
country: France
facility: Saint Antoine
city: Poitiers
country: France
facility: Hopital Jean Bernard
city: Reims
country: France
facility: Robert Debre
city: Rennes
country: France
facility: CHU Hopital Sud
city: Rouen
country: France
facility: Henri Becquerel
city: Tours
country: France
facility: CHRU Tours
city: Bremen
country: Germany
facility: Klinikum Bremen
city: Cologne
country: Germany
facility: University of Cologne
city: Dresden
country: Germany
facility: University Hospital
city: Hamburg
country: Germany
facility: University Hospital
city: Hannover
country: Germany
facility: Medizinische Hochschule
city: Leipzig
country: Germany
facility: Uniklinik Leipzig
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig-Hostein
city: Wiesbaden
country: Germany
facility: DKD Wiesbaden
city: Wurzburg
country: Germany
facility: Medizinische und Poliklinik II
city: Budapest
country: Hungary
facility: St Laszlo Hospital
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Haifa
country: Israel
facility: Rambam MC
city: Tel Hashomer
country: Israel
facility: Sheba MC
city: Alessandria
country: Italy
facility: Ospedale SS. Antonio e Biagio e Cesare Arrigo
city: Bergamo
country: Italy
facility: Ospedale Riuniti
city: Brescia
country: Italy
facility: AO Spedali Civili di Brescia
city: Catania
country: Italy
facility: Ospedale Maggiore
city: Milan
country: Italy
facility: Ospedale Maggiore
city: Naples
country: Italy
facility: Federico II
city: Palermo
country: Italy
facility: V. Cervello
city: Reggio di Calabria
country: Italy
facility: Azienda Ospedale BMM
city: Rome
country: Italy
facility: A.O.S. Andrea
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Kantonsspital
city: Bellinzona
country: Switzerland
facility: IOSI, Ospedale Civico
city: Bern
country: Switzerland
facility: Inselspital
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire
city: Lausanne
country: Switzerland
facility: CHUV
city: Thun
country: Switzerland
facility: LA Onkologie/Medizin
city: Zurich
country: Switzerland
facility: Stadtdpital Triemli
city: Zurich
country: Switzerland
facility: UniversitatsSpital
city: Birmingham
country: United Kingdom
facility: Heartlands Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes
city: Swindon
country: United Kingdom
facility: Great Western Hospital
Study officials:
affiliation: Hôpial Saint Antoine, Paris, France - <laurent.garderet@sat.aphp.fr>
name: Laurent Garderet, MD
role: PRINCIPAL_INVESTIGATOR
References: