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 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To determine the disease response at 6 and 12 months following autologous stem cell transplantation (ASCT) consolidated by bortezomib therapy. This tests the hypothesis that the intervention improves disease response following ASCT • To evaluate the safety, toxicity and tolerability of bortezomib as consolidation therapy following high dose melphalan (HDT) with Melphalan (200mg/m2) and ASCT. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the quality of life of patients receiving bortezomib consolidation after ASCT. • To determine the 2-year progression free survival (PFS) and median PFS after HDT and ASCT followed by consolidation with bortezomib. • To determine the effect of bortezomib on osteoblast and osteoclast function in patients following HDT and ASCT. • To assess MRD status at 6 and 12 months after ASCT consolidated by bortezomib. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The observational substudy is included in the main trial protocol. Patients who decline to take part in the main trial will be invited to participate in an observational sub-study that involves an extra blood sample at their regular 3 & 6 month restaging investigations. This patient group will serve as controls (to the experimental patient group receiving bortezomib) only, for the effect of bortezomib on osteoblast and osteoclast markers. The aim is to recruit a total of 20 patients in this group. |
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E.3 | Principal inclusion criteria |
• Diagnosed with symptomatic (including non-secretory) multiple myeloma • Patient will have received high dose Melphalan with ASCT 3-4 months previously and have at least stable disease (i.e. do not have progressive disease) • Age 18 - 70 years • Life expectancy >6 months • Patients must be able to give written informed consent • Creatinine <400µmol/L • Bilirubin <3x upper limit of normal • ECOG performance status 0-2 • Agreed compliance with recommended contraceptive precautions where appropriate |
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E.4 | Principal exclusion criteria |
• Received bortezomib at any point prior to commencing this trial Received bisphosphonate therapy since ASCT • On, or planned for systemic steroid therapy (e.g. Dexamethasone or prednisolone). Local steroid therapy (e.g. inhaled corticosteroids for asthma or topical corticosteroids for eczema) are allowed • Disease progression at any stage during/after high dose therapy • Past history of polio, cord compression or other significant neurological problems resulting in persisting neurological deficit Grade 2 or greater Severe hepatic impairment, indicated by bilirubin ≥3x upper limit of normal, or AST/ALT >2.5x upper limit of normal • Pregnant or lactating women. Women of childbearing potential* must have a negative blood pregnancy test within 24 hours of starting study drug and must agree to appropriate contraceptive use. • Patient has a history of allergic reaction attributable to compounds containing boron or mannitol • Severe cardiovascular disease including myocardial infarction within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure (Appendix 3, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis • History of hypotension or has decreased blood pressure (sitting systolic blood pressure [SBP] ≤100 mmHg and/or sitting diastolic blood pressure [DBP] ≤60 mmHg) • Peripheral neuropathy or neuropathic pain Grade 2 or higher as defined by NCI CTCAE version 3 • 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Disease response at 6 and 12 months following autologous stem cell transplantation (ASCT) consolidated by bortezomib therapy. Disease responses are as defined in the International Uniform response criteria, ref. Durie et al, Leukaemia, 2007 Safety and tolerability of bortezomib consolidation therapy starting at 3 months post high dose melphalan and autologous stem cell. |
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E.5.2 | Secondary end point(s) |
To determine the effect of bortezomib on osteoblast and osteoclast function in patients following HDT and ASCT. To determine the effect of bortezomib consolidation on MRD status at 6 and 12 months post ASCT. To determine the 2-year progression free survival (PFS) and median PFS after HDT and ASCT followed by consolidation with bortezomib. To evaluate the quality of life of patients receiving bortezomib consolidation after ASCT. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Sub-study control group who will receive no IMP and have blood samples for bone mmarker assays |
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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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 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 | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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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The trial will end when the last patient has completed their 12 month visit. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |