E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Infection risk in mulitple myeloma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021804 |
E.1.2 | Term | Infection bacterial |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10028229 |
E.1.2 | Term | Multiple myelomas |
E.1.2 | System Organ Class | 100000004851 |
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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 compare the frequency of infections in patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observation |
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E.2.2 | Secondary objectives of the trial |
• To assess very good partial response and other markers of effect in the group of patients treated with clarithromycin compared to the other patients
• To assess the tolerability of clarithromycin and sulfamethoxazole/trimethoprim combined with standard therapy in patients with newly diagnosed multiple myeloma
• To estimate overall survival in the three treatment groups
• To assess quality of life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Myeloma diagnosis according to IMWG criteria
• Treatment demanding disease
• Signed informed consent given prior to any study related activities, except bone marrow samples for diagnosis, FISH or biobanking, and skeletal x-ray
• Age > 18 years |
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E.4 | Principal exclusion criteria |
• Allogeneic transplantation scheduled as a part of the treatment
• High-dose melphalan with stem cell support scheduled as a part of the treatment
• Myeloma treatment prior to entry in the study, except radiotherapy, bisphosphonates/denusumab or corticosteroids for symptom control
• Concurrent disease making clarithromycin or sulfamethoxazole/trimethoprim treatment unsuitable
• Positive pregnancy test (only applicable for women with childbearing potential)
• Known or suspected hypersensitivity or intolerance to claritromycin, sulfamethoxazole or trimethoprim
• Prolonged QT corrected (QTc) interval ( > 500 msec on screening ECG)
• Concurrent treatment with cabergoline, fluconazole, ketoconazole, pimozide, quetiapine, sirolimus, verapamil, tacrolimus, ergot alkaloid or methotrexate
• Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, uncontrolled angina or known cardiac amyloi-dosis
• Severe renal dysfunction (estimated creatinine clearance <10 mL/min)
• Serious medical or psychiatric illness which, in the judgment of the investiga-tor, would make the patient inappropriate for entry into the study
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the frequency of infections in patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observation.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The statistical analysis of data will start in the autumn of 2016 when the last included patient has been followed for nine months after randomization |
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E.5.2 | Secondary end point(s) |
To assess very good partial response and other markers of effect in the group of patients treated with clarithromycin compared to the other patients
To assess the tolerability of clarithromycin and sulfamethoxa-zole/trimethoprim combined with standard therapy in patients with newly diagnosed multiple myeloma.
To estimate overall survival in the three treatment groups.
To assess quality of life
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The statistical analysis of data will start in the autumn of 2016 when the last included patient has been followed for nine months after randomization |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 9 |
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 | 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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Inclusion of the 300 patients is expected to start January 2013 and continue until December 2015. The statistical analysis of data will start in the autumn of 2016 when the last included patient has been followed for nine months after randomization. The manuscript should be ready for submission approximately 6 months after termination of follow-up (spring 2017). |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |