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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00256776
• Other study ID #: EudraCT: 2005-001628-35
• Secondary ID: EBMT-CLWP: 42206
• Status: Terminated
• Phase: Phase 3
• Start date: July 2005
• Est. completion date: December 2015

Study information

• Verified date: September 2021
• Source: European Society for Blood and Marrow Transplantation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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 information / eligibility

• Status: Terminated
• Enrollment: 269
• Est. completion date: December 2015
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (ß-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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Velcade (Bortezomib)

• Thalidomide

• Dexamethasone

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
European Society for Blood and Marrow Transplantation	Celgene Corporation, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Countries where clinical trial is conducted

Austria,  Belgium,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median Time to Progression (TTP)		3 year
Secondary	Progression Free Survival		3 year
Secondary	Overall Survival (Interval Between Date of Randomization and Death From Any Cause		1 year
Secondary	Response Rate (Proportion of Subjects Who Achieve Complete, Partial, or Minimal Response)		1 year

External Links

•   Sponsor's website