E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Tumor Lysis Syndrome |
Síndrome de lisis tumoral |
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E.1.1.1 | Medical condition in easily understood language |
Tumor Lysis Syndrome results from the rapid killing of a large quantity of tumor cells which occurs most often after the start of chemotherapy in patients with hematologic cancers. |
Síndrome de lisis tumoral: resultado de la rápida muerte de una gran cantidad de células tumorales que ocurre sobre todo después del inicio de la quimioterapia en pacientes con cánceres hematológicos |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
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 | 10045152 |
E.1.2 | Term | Tumor lysis syndrome |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10045170 |
E.1.2 | Term | Tumour lysis syndrome |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
The primary objective of this trial is to compare the efficacy of Febuxostat with Allopurinol, in terms of sUA level control and preservation of renal function after seven days of treatment (Day 8) starting from 2 days prior to chemotherapy (Day 1). |
El objetivo principal de este ensayo es comparar la eficacia de Febuxostat y Alopurinol en cuanto al control de la concentración de AUs y el mantenimiento de la función renal después de siete días de tratamiento (día 8) desde dos días antes de la quimioterapia (día 1). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: * To compare the efficacy of Febuxostat with Allopurinol, in terms of: - maintenance of sUA levels < 7.5 mg/dL - occurrence of LTLS according to Cairo-Bishop criteria (see study protocol Appendix I, section 13.1) - occurrence of CTLS according to Cairo-Bishop criteria (see study protocol Appendix I, section 13.1) * To compare the safety of Febuxostat with Allopurinol. |
Los objetivos secundarios de este estudio son: * Comparar la eficacia de Febuxostat y Alopurinol, en cuanto a: - mantenimiento de concentraciones de AUs < 7,5 mg/dl, - aparición de SLTA según los criterios de Cairo-Bishop (véase el Apéndice I, sección 13.1). - aparición de SLTC según los criterios de Cairo-Bishop (véase el Apéndice I, sección 13.1). * Comparar la seguridad de Febuxostat y Alopurinol. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female patients a. aged >= 18 years, and b. scheduled for first cytotoxic chemotherapy cycle, regardless of the line of treatment, because of hematologic malignancies, and c. at intermediate or high risk of TLS (see Appendix II, section 13.2 of study protocol for risk stratification), and d. with sUA levels < 10 mg/dL at randomization (Visit 1), and e. candidate to Allopurinol treatment or have no access to Rasburicase. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3. 3. Female of childbearing potential may be enrolled providing a negative pregnancy test at screening and using a highly effective method of birth control resulting in a low failure rate (i.e. less than 1% per year). 4. Able to give written informed consent before any study related procedure. 5. Able to attend all the visits scheduled in the study. 6. Life expectancy > 1 months. |
1. Varones o mujeres a. edad >=18 años, y b. tener programado un primer ciclo de quimioterapia citotóxica, con independencia de la línea de tratamiento, por neoplasias malignas hematológicas, y c. con riesgo intermedio o alto de SLT (véase el Apéndice II, sección 13.2 para la estratificación del riesgo) y d. con concentraciones de AUs <10 mg/dl en el momento de la aleatorización (visita 1), y e. candidatos a tratamiento con Alopurinol o sin acceso a Rasburicasa. 2. Estado funcional de 0 a 3 del Eastern Cooperative Oncology Group (ECOG). 3. Las mujeres en edad fértil podrán participar siempre que tengan una prueba de embarazo negativa en la selección y utilicen un método anticonceptivo muy eficaz con una tasa baja de fracasos (es decir, inferior al 1% anual). 4. Capacidad para otorgar el consentimiento informado por escrito antes de cualquier procedimiento relacionado con el estudio. 5. Capacidad para acudir a todas las visitas programadas del estudio. 6. Esperanza de vida > 1 mes. |
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E.4 | Principal exclusion criteria |
1. Patients known to be hypersensitive to Febuxostat or Allopurinol or to any of the components of the formulations. 2. Patients with hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose-galactase malabsorption. 3. Patients with ischemic heart disease or congestive heart failure (CHF). 4. Pregnant or breast feeding women. 5. Patients with sUA levels >= 10 mg/dL at randomization (Visit 1). 6. Patients receiving Febuxostat, Allopurinol or any other urate lowering therapy (e.g. Rasburicase, probenecid) within 30 days prior to randomization. 7. Patients receiving mercaptopurine and azathioprine within 14 days prior to randomization. 8. High risk patients NOT candidate to Allopurinol treatment. 9. Patients with severe renal insufficiency. 10. Patients with severe hepatic insufficiency. 11. Patients with diagnosis of LTLS or CTLS at randomization (Visit 1). 12. Patients with any serious concomitant illness which, in the opinion of the Investigator, is incompatible with the protocol. 13. Patients receiving any other investigational agent within 30 days prior to randomization (Visit 1). |
1. Hipersensibilidad conocida a Febuxostat o Alopurinol o a cualquiera de los componentes de las formulaciones. 2. Problemas hereditarios de intolerancia a la galactosa, carencia de lactasa lapp o malabsorción de glucosa-galactosa. 3. Cardiopatía isquémica o insuficiencia cardiaca congestiva (ICC). 4. Embarazo o lactancia materna 5. Concentraciones de AUs >= 10 mg/dl en el momento de la aleatorización (visita 1). 6. Tratamiento con Febuxostat, Alopurinol o cualquier otro medicamento reductor del urato (p. ej., Rasburicasa, probenecid) en los 30 previos a la aleatorización. 7. Tratamiento con mercaptopurina y azatioprina en los 14 previos a la aleatorización. 8. Pacientes de alto riesgo NO candidatos a tratamiento con Alopurinol. 9. Insuficiencia renal grave. 10. Insuficiencia hepática grave. 11. Pacientes con diagnóstico de SLTA o SLTC en la aleatorización (visita 1). 12. Cualquier enfermedad concomitante grave que, en opinión del Investigador, sea incompatible con el protocolo. 13. Tratamiento con otro fármaco en investigación en los 30 días previos a la aleatorización (visita 1). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy analysis will be based on the following co-primary endpoints: - Area under the curve of sUA from baseline (Day 1) to the evaluation visit (Day 8) (AUC sUA 1-8). - Change in serum creatinine level from baseline (Day 1) to the evaluation visit (Day 8). |
El análisis principal de la eficacia se basará en los siguientes criterios de valoración principales: - Área bajo la curva del AUs desde el momento basal (día 1) hasta la visita de evaluación (día 8) (AUC1-8 del AUs). - Variación de la concentración sérica de creatinina desde el momento basal (día 1) hasta la visita de evaluación (día 8). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from baseline (Day 1) to the evaluation visit (Day 8) |
Desde el momento basal (Día 1) hasta la visita de evaluación (Día 8) |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints are: - Assessment of treatment responder rate, where treatment response is defined as the maintenance of sUA <= 7.5 mg/dL from the start of chemotherapy (Day 3) to the evaluation visit (Day 8); treatment failure is defined as the presence of two or more consecutive values of sUA missing or > 7.5 mg/dL. The assessment will be based on the central laboratory result. - Assessment of LTLS, from start of chemotherapy (Day 3) to the evaluation visit (Day 8) based on local laboratory results. According to Cairo-Bishop definition LTLS is defined by the presence of 2 or more laboratory abnormalities including: a 25% increase or levels above normal for serum uric acid, potassium, and phosphate or a 25% decrease or levels below normal for calcium. For details, please refer to appendix 13.1.of the study protocol. - Assessment of CTLS, from start of chemotherapy (Day 3) to the evaluation visit (Day 8). According to Cairo-Bishop definition, CTLS is defined by the presence of LTLS in addition to 1 or more of the following significant clinical complications: renal insufficiency, cardiac arrhythmias, sudden death and seizures. The grade of CTLS is defined by the maximal grade of the clinical manifestation. For details, please refer to appendix 13.1.of the study protocol. |
Los criterios de valoración secundarios de la eficacia son: - Evaluación de la tasa de respondedores al tratamiento, definiendo la respuesta al tratamiento como el mantenimiento de un AUs <= 7,5 mg/dl desde el inicio de la quimioterapia (día 3) hasta la visita de evaluación (día 8); el fracaso del tratamiento se define como la presencia de dos o más valores consecutivos de AUs omitidos o >7,5 mg/dl. La evaluación se basará en el resultado del laboratorio central. - Evaluación del SLTA, desde el inicio de la quimioterapia (día 3) hasta la visita de evaluación (día 8), basada en los resultados del laboratorio local. Según la definición de Cairo-Bishop, el SLTA se define por la presencia de 2 o más anomalías analíticas, a saber: aumento del 25% o concentraciones séricas superiores a las normales de ácido úrico, potasio y fosfato o disminución del 25% o concentraciones de calcio inferiores a las normales. Véanse los detalles en el Apéndice 13.1. - Evaluación del SLTC, desde el inicio de la quimioterapia (día 3) hasta la visita de evaluación (día 8). Según la definición de Cairo-Bishop, el SLTC se define por la presencia de SLTA además de 1 o más de las siguientes complicaciones clínicas importantes: insuficiencia renal, arritmias cardíacas, muerte súbita y crisis convulsivas. El grado de SLTC se define por el grado máximo de la manifestación clínica. Véanse los detalles en el Apéndice 13.1. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
from start of chemotherapy (Day 3) to the evaluation visit (Day 8) |
Desde el inicio de la quimioterapia (Día 3) hasta la visita de evaluación (Día 8) |
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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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
France |
Germany |
Hungary |
Italy |
Romania |
Russian Federation |
Spain |
Ukraine |
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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 follow up visit of the last patient |
última visita de seguimiento del último paciente |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |