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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2012 by European Group for Blood and Marrow Transplantation.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Celgene Corporation
Information provided by (Responsible Party):
European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier:
NCT00256776
First received: November 21, 2005
Last updated: August 6, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Velcade (Bortezomib)
Drug: Thalidomide
Drug: Dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by European Group for Blood and Marrow Transplantation:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival (interval between date of randomization and death from any cause [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Response rate (proportion of subjects who achieve complete, partial, or minimal response) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 269
Study Start Date: July 2005
Estimated Study Completion Date: June 2013
Arms Assigned Interventions
Experimental: Thal + Dex + Velcade Drug: Velcade (Bortezomib) Drug: Thalidomide Drug: Dexamethasone
Active Comparator: Thal + Dex
Standard treatment
Drug: Thalidomide Drug: Dexamethasone

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00256776

  Show 81 Study Locations
Sponsors and Collaborators
European Group for Blood and Marrow Transplantation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Celgene Corporation
Investigators
Principal Investigator: Laurent Garderet, MD Hôpial Saint Antoine, Paris, France - <laurent.garderet@sat.aphp.fr>
  More Information

No publications provided

Responsible Party: European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier: NCT00256776     History of Changes
Other Study ID Numbers: EudraCT: 2005-001628-35, EBMT-CLWP: 42206611
Study First Received: November 21, 2005
Last Updated: August 6, 2012
Health Authority: Austria: Federal Ministry for Health and Women
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Czech Republic: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: Ministry of Health
Israel: Ministry of Health
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by European Group for Blood and Marrow Transplantation:
Multiple Myeloma
Velcade
Autologous transplantation
Relapse
Disease progress

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on August 28, 2014