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 - MMVAR

• Register: EUCTR
• Last refreshed on: 27 January 2014
• Main ID: EUCTR2005-001628-35-CZ
• Date of registration: 21/08/2006
• Prospective Registration: Yes
• Primary sponsor: The European group for Blood and Marrow Transplantation (EBMT)
• Public 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 - MMVAR
• Scientific 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 - MMVAR
• Date of first enrolment: 21/08/2006
• Target sample size: 452
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-001628-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: Double blind: Parallel group: yes Cross over: Other: If controlled, specify comparator, Other Medicinial Product: yes Placebo: Other:

Countries of recruitment

Austria, Czech Republic, Germany, Hungary, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Each patient must meet all of the following inclusion criteria to be enrolled in the study:
•Male or female and at least 18 years-of-age
•Histologically confirmed diagnosis of multiple myeloma with evaluable disease parameters (see attachment, Criteria for the diagnosis of myeloma)
•Relapsing or having a progressive disease at least one year after an autologous transplantation as defined by Bladé et al criteria (section 8.2) :
•Relapse as defined by one of the following:
1. Reappearance of serum or urinary paraprotein in immunofixation or routine electrophoresis, confirmed by at least one further investigation and excluding oligoclonal immune reconstitution.
2. >5% plasma cells in a bone marrow aspirate or on trephine bone biopsy
3. Development of new lytic bone lesions or soft tissue plasmacytomas or definite increase in the size of residual bone lesions. Development of a compression fracture does not exclude response.
4. Development of hypercalcemia, corrected serum calcium >11.5mg/dL or 2.8 mmol/L, that is not attributable to any other cause

• Progressive disease as defined by one of the following:
- 1/ > 25% increase in the level of the serum monoclonal paraprotein (5 g/l increase minimum and at least two investigations)
- 2/ > 25% increase in the 24 h urinary light chain excretion (200 mg/d increase minimum and at least two investigations)
- 3/ > 25% increase in plasma cells in a bone marrow aspirate (absolute increase of at least 10%)
- 4/ increase in the size of existing bone lesions or soft tissue plasmacytomas
- 5/ new bone lesions or soft tissue plasmacytomas
- 6/ onset of hypercalcemia not attributable to any other cause

• Measurable disease defined as: quantifiable serum monoclonal antibody defined as a serum monoclonal protein >1g/dL for IgG, or >0.5g/dL for IgA
• Karnofsky performance status > 50 %
• Life expectancy of at least 3 months
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.. Male subject agrees to use an acceptable method for contraception for the duration of the study.
• Negative serum or urine ß-HCG pregnancy test at screening for subjects of child-bearing potential
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Are the trial subjects under 18?
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
• Patients with non-secretory MM
• Karnofsky performance status < or equal to 50%
• Patient has a platelet count < 40,000 ? 109/L within 14 days before enrollment.
• Patient has an absolute neutrophil count <1.0 ? 109/L within 14 days before enrollment.
• Patient has a calculated or measured creatinine clearance <30 mL/minute within 14 days before enrollment.
• Patient has ?Grade 2 peripheral neuropathy within 14 days before enrollment.
• Seropositive for HIV, or active hepatitis A, B or C infection
• Patient has hypersensitivity to bortezomib, boron or mannitol.
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum ?-human chorionic gonadotropin (?-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patient has received other investigational drugs with 14 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Previous or concurrent malignancies at other sites, with the exception of appropriately treated localized epithelial skin or cervical cancer. Patients with remote histories (>5 years) of other cured tumors may be entered
• Poorly controlled hypertension or diabetes mellitus or other serious medical or psychiatric conditions that could interfere with adherence to or completion of this study
• Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Male or female subjects with multiple myeloma who received at least one autologous transplantation and who have responded and later progressed or relapsed at least one year after transplantation.

Intervention(s)

Trade Name: Velcade
Product Name: Velcade
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: bortezomid
CAS Number: 179324-69-7
Current Sponsor code: 26866138
Other descriptive name: Boronic Acid: [(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 3,5-

Product Name: Thalidomide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Thalidomide
CAS Number: 50-35-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
CAS Number: 50-35-1
Concentration unit: mg milligram(s)
Concentration type: equal

Product Name: Dexamethasone
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0,5-

Primary Outcome(s)

Primary end point(s): The primary endpoint of this study is time to progression (TTP): the interval between the date of randomization and the date of disease progression. Death without documented progression will be treated as a competing risk for curve estimation purposes and as a censoring event for significance testing in the framework of the Cox proportional hazards model. Subjects who are progression-free at the time of data cutoff for an analysis or are lost to follow-up will be censored for TTP at the time of their last tumor assessment. The date of progressive disease (PD) will be determined as the date of the first indication of progression using the EBMT criteria.

Secondary Objective: Compare the treatment groups for : overall survival; response rate (complete + partial + minimal) using standard criteria and treatment related complications.

Main Objective: 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 ID(s)

2005-001628-35-DE

X05140