E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myeloma related bone disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
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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 |
The primary objective is to assess the effect of bortezomib on myeloma related bone disease by analyzing bone mineral density (BMD). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are assessment of safety profile and additional efficacy parameters including change in BMD over time, biochemical bone markers, Karnofsky performance status, skeletal events, appearance of new bone lesions, quality of life assessment, progression-free survival, the overall survival, and the respective one-year survival of the subjects treated with Velcade® or observation. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Man or woman over 18 years of age 2. Response of PR or better after receiving high-dose chemotherapy followed by autologous stem cell transplantation (single- or double transplant) as primary therapy of the disease. Date of hospital discharge from stem cell transplantation has to be at least 60 days and within 120 days prior to randomization. 3. Karnofsky performance status of ≥ 60 4. Life expectancy estimated at screening of at least 12 months 5. Following pre-treatment laboratory criteria at and within 14 days before baseline (Day 1 of Cycle 1, before study drug administration): Platelet count ≥ 50x 109/L without transfusion support within the 7 days before the test Haemoglobin ≥ 7.5 g/dL without transfusion support within the 7 days before the test Absolute neutrophil count (ANC) ≥ 0.75 x10 9/L without the use of colony stimulating factors within 14 days before the test Corrected serum calcium < 14 mg/dL (3.5 mmol/L) Aspartate transaminase (AST): <= 2.5 x the upper limit of normal (ULN) Alanine transaminase (ALT): <= 2.5 x ULN Total bilirubin: <= 1.5 x ULN 6. Medically stable on the basis of physical examination, medical history, and vital signs, performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population.
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E.4 | Principal exclusion criteria |
Exclision criteria 1. Received another antimyeloma or experimental therapy following autologous stem cell transplantation 2. Known allergies, hypersensitivity, or intolerance to study drug(s) or its excipients (refer to section 14.1 Physical Description of Study Drug(s)) 3. Use of Velcade® in the previous line of therapy and/or the subject received Velcade® in a previous trial 4. Oligosecretory or non-secretory multiple myeloma 5. Peripheral neuropathy or neuropathic pain of grade 2 or greater intensity, as defined by the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI CTCAE), version 3.0 6. Myocardial infarction within 6 months of enrolment or heart failure NYHA (New York Heart Association) Class III or IV, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities 7. Poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol 8. Treated for a cancer other than multiple myeloma within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ 9. Known to be human immunodeficiency virus (HIV)-positive. Subjects assessed by the investigator to be at risk for HIV infection should be tested in accordance with local policies. 10. Known to be Hepatitis B surface antigen-positive or known active hepatitis C infection. (Subjects assessed by the investigator to be at risk for hepatitis B or C infection are to be tested in accordance with local regulations.) 11. Active systemic infection requiring treatment
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy criterion will be effect of bortezomib on myeloma related bone disease as measured by the change in bone mineral density (BMD) at EOT Visit compared to the baseline value. It is expected that at EOT Visit bone mineral density will be reduced to a greater extent compared to baseline in the untreated group versus subjects treated with Velcade® assuming no significant differences between both groups at baseline. |
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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 | Yes |
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 | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |