E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10028229 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of Bortezomib in increasing the rate of complete remission before mobilization therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to determine whether the addition of the combination Velcade+Dexamethasone in the induction phase of a high-dose program in subjects with previously untreated multiple myeloma who are candidates to high-dose therapy improves the following: time to progression (TTP) progression free survival (PFS), overall survival (OS), response rate (CR+PR), time to response, and duration of response. Feasibility and toxicity of the protocol will be also assessed. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects must satisfy the following criteria to be enrolled in the study: Diagnosis of multiple myeloma II/III clinical stage (Durie and Salmon [see attachment 1]), or I stage in progression previously untreated Age </= 65 years Absence of severe associated pulmonary, cardiac, metabolic, neurologic diseases or concomitant neoplasia Negativity of HBV, HCV, HIV Performance status score >/= 60% Agree to use as acceptable barrier methods for contraception for the duration of the induction phase (for male subject). If female subjects are still having menstrual periods and are not surgically sterile, they must be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study and have negative serum beta-HCG pregnancy at screening. Have pre-treatment clinical laboratory values meeting the following criteria within 14 days before enrollment: Platelet count >/= 100x109/L Haemoglobin >/= 8 g/dL (prior RBC transfusion or recombinant human erythropoietin use is allowed) Absolute neutrophil count (ANC) >/=1.0 x109/L Aspartate aminotransferase (AST) </= 2.5 times the upper limit of normal Alanine aminotransferase (ALT) </= 2.5 times the upper limit of normal Total bilirubin </= 1.5 times the upper limit of normal Serum creatinine </= 2 mg/dL the upper limit Corrected serum calcium <14 mg/dL Written informed consent |
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E.4 | Principal exclusion criteria |
Potential subjects who meet any of the following criteria will be excluded from participating in the study: Diagnosis of smoldering myeloma or MGUS or Waldenstroms disease or other conditions in which IgM M-protein is presenting the absence of a clonal plasma cell infiltration with lytic bone lesions. Prior or current systemic therapy for multiple myeloma including steroids (with the exception of emergency use of a short course [maximum 4 days] of steroids before randomisation Radiotherapy within 30 days before entry Plasmapheresis within 30 days before entry Major surgery within 30 days before entry Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug 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 History of hypotension or has decreased blood pressure Pregnant or breastfeeding Neuropathy Grade 2 Receipt of extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy before enrollment Serious medical or psychiatric illness likely to interfere with participation in this clinical study Have received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study Other malignancy within the past 5 years. Exceptions for the following if treated and not active: basal cell or non metastatic squamous cell carcinome of the skin, cervical carcinoma in situ or International Federation of Gynaecology and Obstetrics stage 1 carcinoma of the cervix. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is the percentage of CR. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |