MMVAR - Velcade: Study of Velcade for the Treatment of Myeloma Patients After Autologous Transplantation

September 21, 2021 updated by: European Society for Blood and Marrow Transplantation

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

269

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria
        • Karl-Franzens
      • Innsbruck, Austria
        • Universitätsklinik
      • Vienna, Austria
        • Wilhelminenspital
      • Vienna, Austria
        • Medizinische Universitaet Wien
  • Belgium
      • Arlon, Belgium
        • St Joseph
      • Baudour, Belgium
        • RHMS
      • Brugge, Belgium
        • AZ St Jan
      • Brussels, Belgium
        • Saint Luc
      • Brussels, Belgium
        • Bordet
      • Brussels, Belgium
        • Erasme CHU
      • Brussels, Belgium
        • University Hospital
      • Gilly, Belgium
        • Saint Joseph
      • Haine-Saint-Paul, Belgium
        • CH Jolimont
      • Ottignies, Belgium
        • Clinique Saint-Pierre
      • Yvoir, Belgium
        • UCL Mont-Godinne
  • Czechia
      • Brno, Czechia
        • University Hospital
      • Olomouc, Czechia
        • Faculty Hospital
  • France
      • Amiens, France
        • CHU Amiens
      • Angers, France
        • CHU Angers
      • Antibes, France
        • Centre Hospitalier d'Antibes
      • Besancon, France
        • CHU Jean Minjoz
      • Bobigny, France
        • Avicenne
      • Bordeaux, France
        • Polyclinique Bordeaux Nord
      • Brest, France
        • Morvan CHU
      • Clermont-Ferrand, France
        • Hotel Dieu
      • Dijon, France
        • ARC CHU Dijon
      • Dunkerque, France
        • Hospitalier de Dunkerque
      • Grenoble, France
        • Hôpital Michallon
      • La Roche sur Yon, France
      • Le Havre, France
        • Centre Hospitalier du Havre
      • Lille, France
        • CHRU de Lille
      • Lyon, France
        • Edouard Herriot
      • Lyon, France
        • Pierre Benite
      • Metz, France
      • Mulhouse, France
        • Centre Hospitalier de Mulhouse
      • Nancy, France
        • Chu Nancy
      • Nantes, France
        • Hotel Dieu
      • Nice, France
        • Archet
      • Paris, France
        • Hopital Cochin
      • Paris, France
        • Hotel Dieu
      • Paris, France
        • Saint Antoine
      • Poitiers, France
        • Hopital Jean Bernard
      • Reims, France
        • Robert Debre
      • Rennes, France
        • Chu Hopital Sud
      • Rouen, France
        • Henri Becquerel
      • Tours, France
        • CHRU Tours
  • Germany
      • Bremen, Germany
        • Klinikum Bremen
      • Cologne, Germany
        • University of Cologne
      • Dresden, Germany
        • University Hospital
      • Hamburg, Germany
        • University Hospital
      • Hannover, Germany
        • Medizinische Hochschule
      • Leipzig, Germany
        • Uniklinik Leipzig
      • Lubeck, Germany
        • Universitatsklinikum Schleswig-Hostein
      • Wiesbaden, Germany
        • Dkd Wiesbaden
      • Wurzburg, Germany
        • Medizinische und Poliklinik II
  • Hungary
      • Budapest, Hungary
        • St Laszlo Hospital
      • Debrecen, Hungary
        • University of Debrecen
  • Israel
      • Haifa, Israel
        • Rambam MC
      • Tel Hashomer, Israel
        • Sheba MC
  • Italy
      • Alessandria, Italy
        • Ospedale SS. Antonio e Biagio e Cesare Arrigo
      • Bergamo, Italy
        • Ospedale Riuniti
      • Brescia, Italy
        • AO Spedali Civili di Brescia
      • Catania, Italy
        • Ospedale Maggiore
      • Milan, Italy
        • Ospedale Maggiore
      • Naples, Italy
        • Federico II
      • Palermo, Italy
        • V. Cervello
      • Reggio di Calabria, Italy
        • Azienda Ospedale BMM
      • Rome, Italy
        • A.O.S. Andrea
  • Switzerland
      • Aarau, Switzerland
        • Kantonsspital Aarau
      • Baden, Switzerland
        • Kantonsspital Baden
      • Basel, Switzerland
        • Kantonsspital
      • Bellinzona, Switzerland
        • IOSI, Ospedale Civico
      • Bern, Switzerland
        • Inselspital
      • Geneva, Switzerland
        • Hôpital Cantonal Universitaire
      • Lausanne, Switzerland
        • CHUV
      • Thun, Switzerland
        • LA Onkologie/Medizin
      • Zurich, Switzerland
        • Stadtdpital Triemli
      • Zurich, Switzerland
        • Universitätsspital
  • United Kingdom
      • Birmingham, United Kingdom
        • Heartlands Hospital
      • Cambridge, United Kingdom
        • Addenbrookes
      • Swindon, United Kingdom
        • Great Western Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Thal + Dex + Velcade
Drug: Dexamethasone
Drug: Thalidomide
Drug: Velcade (Bortezomib)
Active Comparator: Thal + Dex
Standard treatment
Drug: Dexamethasone
Drug: Thalidomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Median Time to Progression (TTP)
Time Frame: 3 year
3 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression Free Survival
Time Frame: 3 year
3 year
Overall Survival (Interval Between Date of Randomization and Death From Any Cause
Time Frame: 1 year
1 year
Response Rate (Proportion of Subjects Who Achieve Complete, Partial, or Minimal Response)
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Society for Blood and Marrow Transplantation

Collaborators

Celgene Corporation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

  • Principal Investigator: Laurent Garderet, MD, Hôpial Saint Antoine, Paris, France - <laurent.garderet@sat.aphp.fr>

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2005

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

November 21, 2005

First Submitted That Met QC Criteria

November 21, 2005

First Posted (Estimate)

November 22, 2005

Study Record Updates

Last Update Posted (Actual)

October 18, 2021

Last Update Submitted That Met QC Criteria

September 21, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EudraCT: 2005-001628-35
  • EBMT-CLWP: 42206611

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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