Multiple MyelomaPhase 3NCT00256776
MMVAR - Velcade: Study of Velcade for the Treatment of Myeloma Patients After Autologous Transplantation
A Phase 3 study testing Velcade (Bortezomib), Thalidomide and Dexamethasone in people with Multiple Myeloma, run by European Society for Blood and Marrow Transplantation at 81 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Velcade (Bortezomib), Thalidomide and Dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 269 participants
- Where
- 81 sitesin 10 countries
- Study dates
- Jul 2005to Dec 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
81 sites in 10 countries.
81 sites in 10 countries
France29 sites
CHU Amiens
Amiens
CHU Angers
Angers
Centre Hospitalier d'Antibes
Antibes
CHU Jean Minjoz
Besançon
Avicenne
Bobigny
Polyclinique Bordeaux Nord
Bordeaux
Morvan CHU
Brest
Hotel Dieu
Clermont-Ferrand
ARC CHU Dijon
Dijon
Hospitalier de Dunkerque
Dunkirk
Hopital Michallon
Grenoble
Study site
La Roche-sur-Yon
Centre Hospitalier du Havre
Le Havre
CHRU de Lille
Lille
Edouard Herriot
Lyon
Pierre Benite
Lyon
Study site
Metz
Centre Hospitalier de Mulhouse
Mulhouse
CHU Nancy
Nancy
Hotel Dieu
Nantes
Archet
Nice
Hopital Cochin
Paris
Hotel Dieu
Paris
Saint Antoine
Paris
Hopital Jean Bernard
Poitiers
Robert Debre
Reims
CHU Hopital Sud
Rennes
Henri Becquerel
Rouen
CHRU Tours
Tours
Belgium11 sites
St Joseph
Arlon
RHMS
Baudour
AZ St Jan
Bruges
Bordet
Brussels
Erasme CHU
Brussels
Saint Luc
Brussels
University Hospital
Brussels
Saint Joseph
Gilly
CH Jolimont
Haine-Saint-Paul
Clinique Saint-Pierre
Ottignies
UCL Mont-Godinne
Yvoir
Switzerland10 sites
Kantonsspital Aarau
Aarau
Kantonsspital Baden
Baden
Kantonsspital
Basel
IOSI, Ospedale Civico
Bellinzona
Inselspital
Bern
Hopital Cantonal Universitaire
Geneva
CHUV
Lausanne
LA Onkologie/Medizin
Thun
Stadtdpital Triemli
Zurich
UniversitatsSpital
Zurich
Germany9 sites
Klinikum Bremen
Bremen
University of Cologne
Cologne
University Hospital
Dresden
University Hospital
Hamburg
Medizinische Hochschule
Hanover
Uniklinik Leipzig
Leipzig
Universitatsklinikum Schleswig-Hostein
Lübeck
DKD Wiesbaden
Wiesbaden
Medizinische und Poliklinik II
Würzburg
Italy9 sites
Ospedale SS. Antonio e Biagio e Cesare Arrigo
Alessandria
Ospedale Riuniti
Bergamo
AO Spedali Civili di Brescia
Brescia
Ospedale Maggiore
Catania
Ospedale Maggiore
Milan
Federico II
Naples
V. Cervello
Palermo
Azienda Ospedale BMM
Reggio Calabria
A.O.S. Andrea
Rome
Austria4 sites
Karl-Franzens
Graz
Universitatsklinik
Innsbruck
Medizinische Universitaet Wien
Vienna
Wilhelminenspital
Vienna
United Kingdom3 sites
Heartlands Hospital
Birmingham
Addenbrookes
Cambridge
Great Western Hospital
Swindon
About this study
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
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.
Read the 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
- Conditions
- Multiple Myeloma
- Being tested
- Velcade (Bortezomib), Thalidomide, Dexamethasone
- Keywords
- Multiple Myeloma, Velcade, Autologous transplantation, Relapse, Disease progress
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Velcade (Bortezomib)Drug
ThalidomideDrug
DexamethasoneDrug
| Study group | Role | What they receive |
|---|---|---|
| Thal + Dex + Velcade | Experimental | Not described Receives: Drug: Velcade (Bortezomib); Drug: Thalidomide; Drug: Dexamethasone |
| Thal + Dex | Active comparator | Standard treatment Receives: Drug: Thalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Time to Progression (TTP)
Measured: 3 year
Secondary outcomes (3)
Progression Free Survival
Measured: 3 year
Overall Survival (Interval Between Date of Randomization and Death From Any Cause
Measured: 1 year
Response Rate (Proportion of Subjects Who Achieve Complete, Partial, or Minimal Response)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2005 (estimated)
- Study startJul 2005
- Primary completionDec 2013
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 269 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Society for Blood and Marrow Transplantation
- Sponsor type
- Research network
- Collaborators
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Laurent Garderet, MD, Principal investigator, Hôpial Saint Antoine, Paris, France - <laurent.garderet@sat.aphp.fr>
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00256776
- Sponsor's protocol ID
- EudraCT: 2005-001628-35
- Other IDs
- EBMT-CLWP: 42206611
- Status last verified
- Sep 2021
- First submitted
- 21 Nov 2005
- Last updated
- 18 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00256776
- Acronym / sponsor ID
- EudraCT: 2005-001628-35
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Velcade, Autologous transplantation, Relapse, Disease progress
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 269 participants (actual)
- Lead sponsor
- European Society for Blood and Marrow TransplantationResearch network
- Collaborators
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Celgene Corporation
- Study start
- Jul 2005
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 22 Nov 2005 (estimated)
- Results
- Posted 18 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Thal + Dex + Velcade | Experimental | Drug: Velcade (Bortezomib), Drug: Thalidomide, Drug: Dexamethasone |
| Thal + Dex | Active comparator | Drug: Thalidomide, Drug: DexamethasoneStandard treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Velcade (Bortezomib) | Drug | Thal + Dex + Velcade |
| Thalidomide | Drug | Thal + Dex, Thal + Dex + Velcade |
| Dexamethasone | Drug | Thal + Dex, Thal + Dex + Velcade |
Primary outcome
Median Time to Progression (TTP)
Time frame: 3 year
3 secondary outcomes
Progression Free Survival
Time frame: 3 year
Overall Survival (Interval Between Date of Randomization and Death From Any Cause
Time frame: 1 year
Response Rate (Proportion of Subjects Who Achieve Complete, Partial, or Minimal Response)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Sponsor's websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laurent Garderet, MD principal investigator
Hôpial Saint Antoine, Paris, France - <laurent.garderet@sat.aphp.fr>
81 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Velcade (Bortezomib), Thalidomide and Dexamethasone in people with Multiple Myeloma, run by European Society for Blood and Marrow Transplantation at 81 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 81 sites in France, Belgium, Switzerland, Germany, Italy and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Time to Progression (TTP) (time frame: 3 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2021.