E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary Prophylaxis of Invasive Fungal Infections |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049085 |
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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 voriconazole as secondary prophylaxis on the rate of occurrence of proven and probable invasive fungal infection (IFI) in allogenic stem cell transplant patients having acute leukemia or acute transformation of chronic myeloid leukemia with previous proven or probable invasive fungal infection from the Day of Transplant until the 12 month Follow-up |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of voriconazole as secondary prophylaxis on the rate of occurrence of proven and probable invasive fungal infection (IFI) from the Day of Transplant until the 6 months Follow-up.
To evaluate the efficacy of voriconazole as secondary prophylaxis on the rate of occurrence of proven and probable invasive fungal infection (IFI) from the Day of Transplant until the End of Prophylaxis.
To evaluate time to occurrence of proven/probable recurrent/new IFIs from the day of transplant in SCT.
To evaluate number of proven/probable recurrent/new IFIs from the day of transplant in SCT.
To evaluate the safety of voriconazole, including overall tolerability (number and type of adverse events)
To evaluate the number of adverse event leading to discontinuation of the study drug.
To evaluate the proportion of patients fungal-free (no fungal infection, no death) at 6 and 12 months after transplant
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Male and female patients with the diagonosis of acute leukemia or acute transformation of chronic myeloic leukemia and with allogenic stem cell transplantation (myeloablative or non-myeloablative regimen), planned in the next 3 weeks and previous proven or probable IFI in the last 6 months, defined according to the MSG/EORTC diagnostic criteria (Ascioglu et al., CID 2002) at the time of the initial diagnosis of IFI, and with no signs or symptoms of active disease.
Signed and dated informed consent will be obtained
Females of childbearing potential must have a negative serum B-HCG pregnancy test and be practicing an effective form of contraception
Age >= 18 years |
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E.4 | Principal exclusion criteria |
Pregnant or lactating women, or women of childbearing potential not using an acceptable method of contraception
Severe disease other than underlying condition, likely to jeopardize the planned termination of the study (e.g. acute myocardial infarction, unstable angina pectoris)
Abnormal baseline findings considered by the investigator to be indicative of conditions that might affect study results (e.g. short bowel syndrome)
Previous history of zygomycosis (eg Mucor, Absidia, Rhizopus)
Positive serum galactomannan antigen test (level 1.5)
Active, symptomatic, uncontrolled IFI (persistence of clinical symptoms related to active fungal disease)
Any biological fungal criterion of active fungal disease as defined by the MSG-EORTC criteria, i.e. persistence of positive microbiological blood cultures or Aspergillus antigenemia, at time of randomization (Appendix E)
Patients with candiduria
Previous failure of voriconazole in the treatment of IFI
Known intolerance to azole compounds
Concomitant use of sirolimus, ergot alkaloids, terfenadine, astemizole, cisapride, pimozide, quinidine, carbamazepine, rifampicin, phenobarbital, ritonavir or efavirenz which might interfere with the evaluation of study drugs during the study specific systemic diseases
Other medical conditions, including HIV-positive serology, that would interfere with the evaluation of the therapeutic response or safety of the study drug
Alcohol and/or any other drug abuse
Previous participation in this trial
Abnormal laboratory test results, defined as impaired hepatic function, as shown by but not limited to (transaminases, alkaline phosphatases, or bilirubin > 5 x Upper Limit of Normal [ULN])
Impaired renal function, as shown by but not limited to estimated creatinine clearance (Clcr) < 50 mL/minute (as per Cockroft-Gault formula (Appendix F)
Any other condition which, in the investigator's judgment, might increase the risk to the subject or decrease the chance of obtaining satisfactory data to achieve the objectives of the study
Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude
Unable and/or unlikely to comprehend and/or follow the protocol
Participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study
Anticipated survival less than 72 hours |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the rate of occurrence of proven or probable invasive fungal infections (IFI) between transplant and the 12 months follow-up, defined according to Ascioglu et al. (CID, 2002) criteria |
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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 | 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) | 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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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.8.3 |
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 | Yes |
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 | 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 | 1 |
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 | 1 |