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 allogeneic stem cell transplant (SCT) patients having acute leukemia or acute transformation of chronic myeloid leukemia (CML) with previous proven or probable IFI from the start of voriconazole prophylaxis until the 12 month Follow-up visit. |
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E.2.2 | Secondary objectives of the trial |
-Evaluate efficacy of voriconazole as secondary prophylaxis on the rate of occurrence of proven & probable IFI from the start of voriconazole prophylaxis until the 6 month Follow-up visit. -Evaluate efficacy of voriconazole as secondary prophylaxis on the rate of occurrence of proven & probable IFI from the start of voriconazole prophylaxis until the End of Prophylaxis visit. -Evaluate time to occurrence of proven/probable recurrent (same pathogen as previous IFI) IFIs from the start of voriconazole prophylaxis. -Evaluate time to occurrence of proven/probable new (new pathogen) IFIs from the start of voriconazole prophylaxis. -Evaluate the proportion of patients experiencing proven/probable recurrent/new IFIs from the start of voriconazole prophylaxis until 12 months after transplant. -Evaluate the proportion of patients who survive free of IFI at 6 & 12 months after transplant. -Evaluate the safety & tolerability of voriconazole as secondary prophylaxis after allogeneic SCT.
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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 previous proven or probable IFI* in the previous six months, who will be receiving allogeneic SCT for acute leukemia or acute transformation of chronic myeloid leukemia. *according to Ascioglu criteria
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, potentially proarryhthmic conditions such as cardiac impairment due to previous cardiotoxic chemotherapy, previous torsade de pointes, prolongation of the QT interval > 450 msec for men or > 470 msec for women)
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 (ratio > or = 1.0)
Active, symptomatic, uncontrolled IFI (persistence of clinical symptoms related to active fungal disease)
Any evidence 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 enrollment (Visit 2)
Present candiduria
Previous failure of voriconazole in the treatment of IFI
Concomitant use of voriconazole 36 hours before chemotherapy until 48 hours after chemotherapy
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)
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) following the start of voriconazole prophylaxis, 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 | Information not present in EudraCT |
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 | 5 |
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 | 5 |