E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory extracranial solid tumors in children and adolescents. |
Tumores sólidos extra-craneales en recaída o refractarios en niños y adolescentes. |
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E.1.1.1 | Medical condition in easily understood language |
Relapsed or refractory extracranial solid tumors in children and adolescents. |
Tumores sólidos extra-craneales en recaída o refractarios en niños y adolescentes. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
Dose confirmation phase: to evaluate the safety of the combination of AloCelyvir added to the cytoreductor scheme (combination of chemotherapy, surgery, radiotherapy). |
Fase de confirmación de dosis: evaluar la seguridad de la combinación de AloCelyvir sumado al esquema citorreductor (combinación de quimioterapia, cirugía, radioterapia) |
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E.2.2 | Secondary objectives of the trial |
•Expansion phase: To measure antitumor activity (measured as objective response rate [complete response and partial response]) of the combination). •Feasibility of the combination. •Antitumor activity (dose confirmation phase). •Security (Expansion phase). •Calculation of progression-free survival. •Calculation of global survival. |
•Fase de expansión: Medida de la actividad antitumoral (medida como tasa de respuesta objetiva [respuesta completa y respuesta parcial] de la combinación) •Viabilidad de la combinación •Actividad antitumoral (Fase de confirmación de dosis) •Seguridad (Fase de expansión) •Cálculo de la supervivencia libre de progresión •Cálculo de la supervivencia global |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients aged between 1 year and ≤21 years. 2. Patients with extra-cranial solid tumor, relapsed or refractory, for which there is no standard curative treatment. 3. Disease measurable or evaluable according to RECIST criteria v1.1. 4. Patients for whom the combination with the proposed chemotherapy and radiotherapy regimens is considered adequate. Patients may have previously received the same schemes. 5. Adequate functional status, organic function (renal, hepatic) and hematological values: o Functional status: Lansky ≥50% and Karnofsky ≥50%. Patients who use a wheelchair due to paralysis associated with the tumor will be considered ambulatory for the assessment of functional status. o Haematological function (dose confirmation phase): Platelets ≥75,000 / μL (without support for 3 days). Total neutrophils ≥750 / μL (without growth factor for 3 days). Hemoglobin ≥ 8 g / dL (transfusions allowed). o Haematological function (expansion phase): Platelets ≥50,000 / μL (without support for 3 days). Total neutrophils ≥500 / μL (without growth factor for 3 days). Hemoglobin ≥ 8 g / dL (transfusions allowed). o Kidney and liver function: Serum creatinine ≤1.5 times the high value of normality. In case of creatinine> 1.5 times the high value of normality, glomerular filtration (estimated by Schwartz, cystatin or other methods)> 60 ml / min / 1.73 m2. Total bilirubin ≤1.5 times the high value of normality. Transaminases (GOT and GPT) ≤3 times the high value of normality. In case of patients with liver metastases ≤5 times the high value of normal. 6. Patient capable of complying with the treatment and plan of visits and evaluations. 7. Life expectancy ≥3 months. 8. Appropriate contraceptive methods for sexually active men and women of childbearing age. 9. Negative pregnancy test for women of childbearing age. 10. Informed consent in writing according to current legislation. 11. Washing periods compared to previous treatments. o At least two weeks of the last dose of chemotherapy. For patients receiving metronomical oral chemotherapy at low doses, this period is at least one week. o At least four weeks after the autologous hematopoietic stem cell transplant. o At least three months after the allogeneic transplant of hematopoietic progenitors. Patients will only be able to enter if they do not have clinically significant active complications derived from the transplant. o At least two weeks after the last focal radiotherapy or six weeks in the case of craniospinal radiation therapy. There is no washing for palliative radiotherapy. Radiotherapy may be part of the treatment of the trial in which case the treatment with Alo-Celyvir will be applied as described in section 6. o At least two weeks or 5 half-lives (whichever occurs earlier) since the last dose of a biological or investigational treatment. |
1.Pacientes con edades comprendidas entre 1 año y ≤ 21 años. 2.Pacientes que presenten tumor sólido extra-craneal en recaída o refractario, para el que no exista tratamiento curativo estándar. 3.Enfermedad medible o evaluable según criterios RECIST v1.1. 4.Pacientes para los que la combinación con los regímenes de quimioterapia y radioterapia propuestos se consideren adecuados. Los pacientes pueden haber recibido anteriormente los mismos esquemas. 5.Adecuados estado funcional, función orgánica (renal, hepática) y valores hematológicos,: oEstado funcional de Lansky ≥50% y de Karnofsky ≥50%. Los pacientes que utilizan silla de ruedas por parálisis asociada al tumor se considerarán ambulatorios para la evaluación del estado funcional. oFunción hematológica (fase de confirmación de dosis) Plaquetas ≥75,000/µL (sin soporte durante 3 días) Neutrófilos totales ≥750/ µL (sin factor de crecimiento durante 3 días) Hemoglobina ≥ 8 g/dL (transfusiones permitidas) oFunción hematológica (fase de expansión) Plaquetas ≥50,000/µL (sin soporte durante 3 días) Neutrófilos totales ≥500/ µL (sin factor de crecimiento durante 3 días) Hemoglobina ≥ 8 g/dL (transfusiones permitidas) oFunción renal y hepática Creatinina sérica ≤1,5 veces el valor alto de la normalidad. En caso de creatinina >1,5 veces el valor alto de la normalidad, filtrado glomerular (estimada por Schwartz, cistatina u otros métodos) >60 ml/min/1,73 m2. Bilirrubina total ≤1,5 veces el valor alto de la normalidad. Transaminasas (GOT y GPT) ≤3 veces el valor alto de la normalidad. En caso de pacientes con metástasis hepáticas ≤5 veces el valor alto de la normalidad 6.Paciente capaz de cumplir con el tratamiento y plan de visitas y evaluaciones. 7.Expectativa de vida ≥3 meses. 8.Métodos anticonceptivos adecuados para los varones sexualmente activos y las mujeres en edad fértil. 9.Test de embarazo negativo para las mujeres en edad fértil. 10.Consentimiento informado por escrito según la legislación vigente. 11.Periodos de lavado respecto a tratamientos previos oAl menos dos semanas de la última dosis de quimioterapia. Para pacientes recibiendo quimioterapia oral metrónomica a bajas dosis, este periodo es de al menos una semana. oAl menos cuatro semanas desde el trasplante autólogo de progenitores hematopoyéticos oAl menos tres meses desde el trasplante alogénico de progenitores hematopoyéticos. El pacientes sólo podrá entrar si no tiene complicaciones activas clínicamente significativas derivadas del trasplante oAl menos dos semanas desde la última radioterapia focal o seis semanas en caso de radioterapia craneoespinal. No hay lavado para la radioterapia paliativa. La radioterapia puede formar parte del tratamiento del ensayo en cuyo caso se aplicará el tratamiento con Alo-Celyvir según se describe en la sección 6. oAl menos dos semanas o 5 vidas medias (el que ocurra antes) desde la última dosis de un tratamiento biológico o investigacional. |
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E.4 | Principal exclusion criteria |
1. Previous treatment with Celyvir. 2. Active acute toxicities of previous treatment grade ≥3 of the CTCAE v4. 3. Known and uncontrolled bacterial, viral, fungal or parastaria active infection. 4. Known active infection for hepatitis or HIV virus. 5. Patients with CNS metastases should be clinically stable and with stable or decreasing doses of steroids for at least one week. 6. Serious active and past systemic diseases that are clinically significant or uncontrolled, which may imply an added risk for the patient. 7. Allergy to Penicillin or its derivatives. |
1.Tratamiento previo con Celyvir 2.Toxicidades agudas activas del tratamiento previo grado ≥3 del CTCAE v4 3.Infección activa bacteriana, viral, fúngica o parastaria conocida no controlada 4.Infección activa conocida por virus de hepatitis o VIH 5.Los pacientes con metástasis del SNC, deberán estar clínicamente estables y con dosis de esteroides estables o en descenso durante al menos una semana. 6.Enfermedades sistémicas activas y pasadas graves clínicamente significativas o no controladas que puedan implicar un riesgo añadido para el paciente. 7.Alergia a Penicilina o sus derivados. |
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E.5 End points |
E.5.1 | Primary end point(s) |
•Dose confirmation phase: Rate of dose-limiting toxicities. |
•Fase de confirmación de dosis: Tasa de toxicidades limitantes de dosis |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Expansion phase: Rate of objective responses (complete and partial responses) of the combination. •Feasibility of the combination: rate of patients who meet selection criteria who can receive at least one cycle of the combination of Alo-Celyvir with chemo-radiotherapy and measurement of the time from recruitment to the preparation and administration of Alo-Celyvir. •Dose confirmation phase: Rate of objective responses (complete and partial responses) of the combination. •Progression free survival. •Global survival. •Rate of adverse events. |
•Fase de expansión: Tasa de respuestas objetivas (respuestas completas y parciales) de la combinación •Viabilidad de la combinación: tasa de pacientes que cumplen criterios de selección que pueden recibir al menos un ciclo de la combinación de Alo-Celyvir con quimio-radioterapia y medida del tiempo desde el reclutamiento hasta la preparación y administración de Alo-Celyvir •Fase de confirmación de dosis: Tasa de respuestas objetivas (respuestas completas y parciales) de la combinación •Supervivencia libre de progresión •Supervivencia global •Tasa de acontecimientos adversos |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | No |
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 | 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 | 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 | 2 |
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 | 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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LVLS (last visit of the last subject) |
LVLS (Última visita del último sujeto) |
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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 | |
E.8.9.1 | In the Member State concerned months | 48 |
E.8.9.1 | In the Member State concerned days | |