E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Invasive pulmonary aspergillosis in patients with acute myeloblastic or lymphoblastic leukaemia. |
Aspergilosis pulmonar invasiva en pacientes con leucemia aguda, mieloblástica o linfoblástica. |
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E.1.1.1 | Medical condition in easily understood language |
Invasive pulmonary infection due to aspergillus fungus in patients with acute myeloblastic or lymphoblastic leukaemia. |
Infección pulmonar invasiva por hongo Aspergillus en pacientes con leucemia aguda, mieloblástica o linfoblástica. |
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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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022881 |
E.1.2 | Term | Invasive bronchopulmonary aspergillosis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 overall tolerability of the drug, defined as any adverse event that results in the interruption of treatment, during primary prophylaxis with nebulized ABLC, in paediatric patients with acute leukaemia (AL) undergoing intensive chemotherapy. |
Evaluar la tolerabilidad global del fármaco, definida como cualquier acontecimiento adverso que suponga la interrupción del tratamiento, durante la profilaxis primaria con ABCL nebulizado, en pacientes pediátricos con leucemia aguda (LA) tratados con quimioterapia intensiva. |
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E.2.2 | Secondary objectives of the trial |
1.To evalute the efficacy of primary prophylaxis with nebulized ABLC on the incidence of invasive pulmonary aspergillosis (IPA) in paediatric patients with LA undergoing intensive chemotherapy. 2.To determine the IPA-related mortality during primary prophylaxis with ABLC in paediatric patients with (AL) undergoing intensive chemotherapy. |
1.Evaluar la eficacia de la profilaxis primaria con ABCL nebulizado sobre la incidencia de aspergilosis pulmonar invasiva (API) en pacientes pediátricos con LA tratados con quimioterapia intensiva. 2.Evaluar la mortalidad relacionada a la API durante la profilaxis primaria con ABCL nebulizado en pacientes pediátricos con LA tratados con quimioterapia intensiva. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age: patients between 3 and 18 years. 2. Diagnosis of myeloblastic or lymphoblstic AL during intensive chemotherapy. 3. Informed consent of parents/guardians and/or assent of the patient has been obtained. |
1.Edad: pacientes menores de entre 3 y 18 años. 2.Diagnóstico de LA mieloblástica o linfoblástica en fase de tratamiento con quimioterapia intensiva. 3.Obtención del consentimiento informado de padres/tutores y/o asentimiento del paciente. |
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E.4 | Principal exclusion criteria |
1.Probable or proven invasive pulmonary fungal infection before entering the trial. 2.Previous chronic renal impairment or baseline serum creatinine > 2.5 mg /dL 3.Severe hepatic impairment. 4.Moderate-severe asthma being treated pharmacologically. 5.Antifungal treatment for filamentous fungi in the last 4 weeks. 6.Participating or have participated in a clinical trial during the last 4 weeks. 7.Mentally retarded 8.Known allergy or hypersensitivity to the active ingredient of the study drug or to any of its excipients. 9.Any serious concomitant disease that in the investigator?s opinion could compromise the completion of the trial or affect the patient?s tolerability to this treatment. 10.Pregnancy (in women of fertile age). 11.Breast-feeding.
Patients are defined as having probable IFI when their radiological image is suggestive of fungal infection and they have positive antigenemia for Aspergillus. IFI would be proven when the presence of Aspergillus is confirmed in aspirate culture or by lung biopsy. |
1.Infección fúngica invasiva pulmonar (IFI) probable o probada antes de entrar en el ensayo. 2.Insuficiencia renal crónica previa o creatinina sérica basal > 2,5 mg /dl 3.Insuficiencia hepática grave. 4.Asma moderado-grave en tratamiento farmacológico. 5.Tratamiento con antifúngicos contra hongos filamentosos en las últimas 4 semanas. 6.Participar o haber participado en un ensayo clínico durante las últimas 4 semanas. 7.Retraso mental. 8.Alergia o hipersensibilidad conocida al principio activo del fármaco en investigación, o a cualquiera de sus excipientes. 9.Cualquier enfermedad concomitante grave que en la opinión del investigador pueda comprometer completar el estudio o afectar la tolerancia del paciente para este tratamiento. 10.Embarazo (en las mujeres en edad fértil). 11.Lactancia.
Se define como IFI probable aquella en los que el paciente presenta una imagen radiológica sugestiva de infección fúngica y antigenemia positiva por Aspergillus. La IFI quedaría probada cuando se confirmara la presencia de Aspegillus en cultivo de aspirado o por biopsia pulmonar |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable will be the proportion of patients who discontinue prophylactic treatment with ABLC due to an adverse event that is related or not to the study drug or for intolerability to it. |
La variable primaria de eficacia será la proporción de pacientes que discontinúan el tratamiento profiláctico con ABCL por un acontecimiento adverso relacionado o no con el fármaco en estudio o por intolerancia al mismo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
They will be analysed by homogeneity tests comparing the results with those of a historical cohort. The hypothesis tests and confidence intervals will be calculated by exact methods given the low sample size. |
Se analizarán mediante pruebas de homogeneidad comparando los resultados observados respecto a la cohorte histórica. Las pruebas de hipótesis e intervalos de confianza se calcularán por métodos exactos dado el bajo tamaño de la muestra. |
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E.5.2 | Secondary end point(s) |
The secondary variables to be obtained are the following:
-Proportion of discontinued drug administrations due to a treatment-related adverse event or intolerability to treatment (number of discontinued administrations/ number of administrations started) -Total number of IPA cases -Incidence of IPA during the ABLC (Abelcet®) prophylactic treatment period (number of patients with IPA/number of patients on prophylaxis). -IPA incidence rate during the ABLC prophylactic treatment period (number of patients with aspergillosis/time on prophylaxis of study patients). -Mortality due to IPA -Percentage of deaths during the prophylactic treatment period and cause of death. |
Se recogerán las siguientes variables secundarias: -Proporción de administraciones del fármaco que discontinúan por un acontecimiento adverso relacionado con el tratamiento o intolerancia al mismo (nº administraciones interrumpidas/nº administraciones iniciadas ) -Número total de casos de API -Incidencia de API durante el período de tratamiento profiláctico con ABLC (Abelcet®) (nº de pacientes con API/nº de pacientes en profilaxis). -Tasa de incidencia de API durante el período de tratamiento profiláctico con ABCL (nº pacientes con aspergilosis/tiempo en profilaxis de los pacientes en estudio) -Mortalidad por API -Porcentaje de fallecidos durante el tratamiento profiláctico y causa de fallecimiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For the analysis of patients who died due to IPA or other causes a Kaplan-Meier survival analysis will be performed. The median survival time and the % of cumulative survival will be estimated with their respective 95% confidence intervals. The 95% confidence interval (95% CI) will be calculated for the presence/absence of toxicity and toxicity severity (CTCAE grades 1 to 4) variable. All the adverse events will be listed giving their severity and relation to the study drug. The categorical variables will be will be summarised by frequency distributions whilst the central tendency and dispersion will be given for the quantitative variables and, if appropriate, their 95% confidence intervals (95% CI). |
Para el análisis de pacientes fallecidos por API u otras causas se realizará un análisis de supervivencia mediante el método de Kaplan-Meier. Se estimarán la mediana del tiempo de supervivencia y el % de supervivencia acumulada, con sus intervalos de confianza respectivos al 95%. En la variable presencia/ausencia de toxicidad y gravedad de toxicidad (grados CTCAE 1 a 4) se calculará su intervalo de confianza (IC95%). Se listarán todos los acontecimientos adversos considerando su gravedad y su relación con el fármaco en estudio. Las variables categóricas se resumirán mediante distribuciones de frecuencias mientras que, para las variables cuantitativas, se informará de tendencia central y dispersión y, si es apropiado, se presentará su intervalo de confianza al 95% (IC95%). |
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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 | 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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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 | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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Last patient last visit will be the end of the trial |
El final del ensayo coincide con la última visita del último sujeto reclutado en el ensayo |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |