Overview

This trial is active, not recruiting.

Condition multiple myeloma
Treatments velcade (bortezomib), thalidomide, dexamethasone
Phase phase 3
Sponsor European Group for Blood and Marrow Transplantation
Collaborator Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Start date July 2005
End date June 2013
Trial size 269 participants
Trial identifier NCT00256776, EBMT-CLWP: 42206611, EudraCT: 2005-001628-35

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
velcade (bortezomib)
thalidomide
dexamethasone
(Active Comparator)
Standard treatment
thalidomide
dexamethasone

Primary Outcomes

Measure
Time to progression, the interval between the date of randomization and date of disease progression (death without progression is a competing risk)
time frame: 1 year

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Principal investigator Laurent Garderet, MD
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
Trial information was received from ClinicalTrials.gov and was last updated in August 2012.
Information provided to ClinicalTrials.gov by European Group for Blood and Marrow Transplantation.