This will be a Phase II, prospective, non-comparative, multicenter, open-label study of the effects of the combination of Bortezomib/Dexamethasone/Zoledronic acid on bone mineral density, skeletal related events and bone metabolism in multiple myeloma patients at first relapse. MedDRA version: 9.1 Level: LLT Classification code 10028228 Term: Multiple myeloma
Conditions
Interventions
Trade Name: VELCADE
Product Name: VELCADE
Product Code: Not available
Pharmaceutical Form: Powder for solution for injection
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Sponsors
Prof. M.A. Dimopoulos
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must satisfy all the following criteria to be enrolled in the study: • myeloma patients at first relapse • age = 18 years • ?arnofsky performance status = 60 (patients with lower performance status due to myeloma bone disease can also be included) • measurable disease • platelet count >50x109/L • neutrophil count >0.75x109/L • hemoglobin =7.0 g/dL (the use of recombinant human erythropoietin or red blood cell transfusions to maintain hemoglobin levels above 7.0 g/dL is not an exclusion criterion) • serum ALT and AST = 3-fold of upper normal limit • serum bilirubin = 2-fold of upper normal limit • serum Calcium = 10.5 mg/dL • expected survival = 2 months • signed informed consent Are the trial subjects under 18? no 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
Exclusion criteria: Potential subjects who meet any of the following criteria will be excluded from participating in the study: • presence of another cancer • serious medical or psychiatric illness likely to interfere with participation in this clinical study • grade 2-4 peripheral neuropathy or neuropathic pain Grade 2 or higher as defined by NCI CTCAE version 3 • pregnant women or breast-feeding • women of childbearing potential not using adequate contraception • known or suspected hypersensitivity or intolerance to bortezomib, boron, mannitol, zoledronic acid, dexamethasone, or heparin (if an indwelling catheter is used) • uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months prior to first dose of study drug) • uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 4, NYHA Classification of Cardiac Disease), uncontrolled angina, pericardial disease, or cardiac amyloidosis • acute diffuse infiltrative pulmonary disease • history of hypotension or patient has decreased blood pressure (sitting systolic blood pressure [SBP] £100 mmHg and/or sitting diastolic blood pressure [DBP] £60 mmHg) • patient has received extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 4 weeks prior to enrolment • patient has received any drugs or agents that inhibit (e.g., cimetidine, erythromycin, fluoxetine, ketoconazole, paroxetine) or induce (e.g., carbamazepine, glucocorticoids, phenobarbital, rifampin) CYP2C19 or CYP3A4 within 14 days before the first dose of VELCADE (proton pump inhibitors are allowed) • need for therapy with concomitant CYP 3A4 inhibitors (e.g., itraconazole, fluconazole, clarithromycin, erythromycin, norfloxacin, fluvoxamine, cimetidine, indinavir, ritonavir) or inducers (e.g., efavirenz, barbiturates, phenytoin, rifampin, glitazones). Proton pump inhibitors are allowed. • Patient has received an experimental drug or has used an experimental medical device within 4 weeks prior to the planned start of treatment. Concurrent participation in non-treatment studies is allowed, provided it will not interfere with participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this clinical trial is: •to evaluate the effects of VELCADE in combination with dexamethasone and zoledronic acid, following 4 cycles of treatment, or at termination of the combination therapy, on Bone Mineral Density (BMD) in patients with Multiple Myeloma at first relapse. ;Secondary Objective: to evaluate the effects: of VELCADE in combination with dexamethasone and zoledronic acid, following 8 cycles of treatment, on Bone Mineral Density (BMD) in patients with Multiple Myeloma at first relapse. of the above combination, following 4 cycles and a total of 8 cycles of treatment, or at termination of the combination therapy, on Bone Metabolism Markers on Bone Pain, on Skeletal Related Events and on Osteolytic Bone Lesions in the same population that 8 cycles of the combination regimen have, 18 months following discontinuation of VELCADE and dexamethasone (but not of zoledronic acid), on BMD, on Bone Markers, on Bone Pain, on Skeletal Related Events and on Osteolytic Bone Lesions in patients who presented with Multiple Myeloma at first relapse and who, following the 8 cycles of the above combination regimen, responded to therapy or achieved a plateau phase of their disease.;Primary end point(s): Bone mineral density (BMD) following 4 cycles of treatment, or at termination of the combination therapy, with the VELCADE/dexamethasone/zoledronic acid combination regimen in patients with Multiple Myeloma at first relapse. | — |
Countries
Greece
Outcome results
None listed