E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Invasive fungal infection in patients with hematological malignancies. |
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E.1.1.1 | Medical condition in easily understood language |
Invasive fungal infection in patients with hematological malignancies. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017544 |
E.1.2 | Term | Fungemia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
The main objective of the trial is to compare two strategies, namely an empirical approach (fever driven) (EAT, arm A) versus pre-emptive (diagnostic driven) (PAT, Arm B) approach, for starting antifungal therapy (with caspofungin) for managing patients treated with chemotherapy for attaining remission induction of acute myeloid leukemia or myelodysplastic syndrome or myeloablation to prepare for an allogeneic HSCT, by assessing the survival rates 42 days (6 weeks) after initial randomization. The intent is to show the non-inferiority of the pre-emptive approach. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are linked to Translational Research:
- To evaluate clinical validity and utility of a standardized Aspergillus PCR proposed by the ISHAM Working Group EAPCRI.
- To evaluate clinical validity and utility of beta-D-glucan.
- To determine the occurrence of SNP and the predictive value of SNP for identifying patients at higher risk of developing invasive fungal infection. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age 18 years or older.
- Start within 3 days before randomization, remission induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that is newly diagnosed or in first relapse after hematological remission lasting for a minimum duration of 6 months OR start within 3 days before randomization, myeloablative conditioning regimen to prepare for an allogeneic HSCT. Permissible conditioning regimens are outlined in Appendix E.
- Planned hospital admission for the duration of the neutropenic phase (ANC< 0.5 x 109 /L).
- Planned oral or intravenous (I.V.) fluconazole for Candida prophylaxis at the dose of 400 mg/day; no other antifungal systemic prophylaxis is allowed.
- Patients with childbearing potential must have a negative serum pregnancy test and use effective contraceptive methods during the treatment period and for at least 3 months after the last study treatment.
- Female subjects who are lactating should discontinue nursing prior to the first dose.
- Adequate contraception in men.
- Patients of childbearing/ reproductive potential should use adequate birth control measures as defined by the investigator. By adequate birth control measures should be understood highly effective methods as defined by the Note 3 of the note for guidance on non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals (CPMP/ICH/286/95):"A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly
such as implants, injectables, combined oral contraceptives, some IDUs, sexual abstinence or
vasectomised partner. For subjects using a hormonal contraceptive method, information regarding the product under evaluation and its potential effect on contraceptives should be addressed."
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
- Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. |
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E.4 | Principal exclusion criteria |
- Previous or current history of proven or probable IFD.
- Current clinical diagnosis of pneumonia.
- Serious uncontrolled concomitant disease or comorbidity that, in the opinion of the investigator, may compromise adherence to the study protocol.
- History of allergy or any adverse reaction to echinocandin drugs (caspofungin, micafungin, or anidulafungin).
- Inadequately treated infection at study entry.
- Documented HIV infection.
- Concomitant inclusion on other clinical trial using an investigational drug for infectious disease. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival at 42 days i.e. 6 weeks after randomization. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
42 days i.e. 6 weeks after randomization |
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E.5.2 | Secondary end point(s) |
Overall survival at 84 days after randomization.
Development of proven or probable IFD during the 42 days (6 weeks) and 84 days (12 weeks)
following randomization.
Correct management, according to allocated treatment arm (i.e. appropriate administration of
caspofungin in compliance to protocol, and compliance to the treatment strategy) during the 42 days (6
weeks) and 84 days after randomization.
Survival free of fungal infection during the 42 and the 84 days following randomization.
Safety as evaluated by AEs and SAEs by CTCAE criteria v4.0.
Number of days under caspofungin treatment or under another antifungal treatment administered after
caspofungin (evaluation will be done at day 42 and day 84 after randomization).
Costs related to the strategy for initiating antifungal treatment and monitor antifungal treatment during
the 42 days and the 84 days following randomization. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All endpoints will be assessed at 2 specific time points: 42 days after randomization and 84 days 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 | 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 |
translational research and cost-effectiveness |
|
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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
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 | No |
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 |
Croatia |
Switzerland |
Turkey |
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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
|
End of study occurs when both of the following criteria have been satisfied:
1. All randomized patients have been followed up until day 84.
2. The database has been fully cleaned and frozen for this analysis. |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |