E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Invasive fungal infections (IFI) in subjects with Acute Lymphoblastic Leukemia (ALL) undergoing remission induction chemotherapy. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017533 |
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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 determine the prophylactic efficacy of AmBisome compared to placebo in preventing IFIs in subjects with ALL undergoing remission-induction chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
• To determine the safety and tolerability of prophylactic AmBisome in subjects with ALL undergoing remission-induction chemotherapy. • To determine the impact of IFI prevention on the efficacy of remission-induction chemotherapy in subjects with ALL. |
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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 |
FARMACOCINETICA/FARMACODINAMICA: Versione:Amend.1 Data:2010/10/13 Titolo:Sottostudio di farmacocinetica. Obiettivi:Ai soggetti randomizzati da un sottogruppo di centri sara` data l’opportunita` di partecipare a un sottostudio di farmacocinetica (PK) che includera` 40 pazienti e avra` lo scopo di determinare i livelli minimi di AmBisome durante il dosaggio bisettimanale. Il monitoraggio della farmacocinetica comportera` il prelievo di un ulteriore campione di sangue per valutare i livelli di AmBisome poco prima di ciascuna infusione del farmaco in studio per le prime quattro settimane. Con lo schema di randomizzazione 2:1 si prevede di ottenere valori di concentrazioni minime di AmBisome per circa 26 soggetti con dosaggio bisettimanale.
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E.3 | Principal inclusion criteria |
• Newly diagnosed ALL receiving an ALL chemotherapy regimen that typically induces at least 10 days of neutropenia. • Age ≥ 18 years. • Able to have all screening tests performed quickly to ensure results can be obtained and evaluated before randomization so that the first dose of randomized study drug for IFI prophylaxis can be administered within 5 days of first remission-induction chemotherapy. • Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of any study procedures. |
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E.4 | Principal exclusion criteria |
• Known hypersensitivity to amphotericin B or AmBisome, the metabolites or formulation excipients, in particular known history of anaphylactic reaction to amphotericin B or AmBisome or any of its metabolites or formulation excipients. • Known hypersensitivity to the excipients of the placebo formulation • Current fever (≥38�C) unless explained by noninfectious causes • Subjects with proven, probable or possible IFI (according to EORTC/MSG criteria) at screening or in subject history • Pulmonary infiltrates • Concomitant or previous treatment with an antifungal drug within the previous 30 days unless the plasma level is below the limit of detection or at least 5 half-lives of the antifungal has elapsed since the treatment was given • Serum creatinine > 2 x the upper limit of the normal range (ULN) • Grade 3 Liver function test results: alanine aminotransferase or aspartate aminotransferase > 5 x ULN; total bilirubin > 2.5 x ULN • Any severe co morbidity other than underlying hematological disease (ALL), which in the investigator’s judgment may interfere with study evaluations or affect the subject’s safety. • Subjects who have taken any investigational drug in the last 30 days prior to screening, with the exception of ALL chemotherapy investigational products being used as part of the subject’s current ALL treatment protocol. • Pregnant or nursing females. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint in support of this objective is the proportion of subjects with proven or probable IFIs during remission-induction chemotherapy for ALL. |
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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 | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 | 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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Ultima visita, ultimo soggetto. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |