E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fanconi anemia |
Anemia de Fanconi |
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E.1.1.1 | Medical condition in easily understood language |
Fanconi anemia |
Anemia de Fanconi |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
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 | 10055206 |
E.1.2 | Term | Fanconi's anemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 is to assess the safety of cell mobilization after treatment with filgrastim and plerixafor in patients with Fanconi Anemia. |
El objetivo principal es determinar la seguridad de la movilización con filgrastim y plerixafor en pacientes diagnosticados de Anemia de Fanconi. |
|
E.2.2 | Secondary objectives of the trial |
- To assess the efficacy of CD34+ cell mobilization after treatment with filgrastim and plerixafor in patients with Fanconi Anemia. - To assess the CD34+ collection eficacy after treatment with high doses of filgrastim and plerixafor in patients with Fanconi Anemia. - To assess the efficacy of the immunomagnetic haematopoietic progenitors selection (CD34+ cells) from the apheresis product |
- Determinar la eficacia de movilización de células CD34+ a sangre periférica en pacientes diagnosticados de Anemia de Fanconi tras el tratamiento con filgrastim y plerixafor - Determinar la eficacia de la colecta de células CD34+ en pacientes diagnosticados de Anemia de Fanconi tras el tratamiento con filgrastim y plerixafor - Determinar la eficacia de la selección inmunomagnética de progenitores hematopoyéticos (células CD34+) del producto de aféresis |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- male or female > 1 year - diagnosed of Fanconi's anemia confirmed by instability chromosomal test with diepoxy-butane or mitomycin C - At least one of the following parameters must be higher than these values: Hemoglobin:8,0 g/dL; neutrophils: 750/mm3; platelets: 30.000/mm3 - Lansky index> 60%. - Left ventricular ejection fraction >50%. - To grant informed consent in agreement with current law norms - Women in childbearing age must obtain a negative result in the pregnancy test in serum or urine in the visit of selection and accept the use of suitable contraceptive methods since at least 14 days prior to the first dose of mobilizing treatment until the 14 days following the last |
- Pacientes con diagnóstico de AF confirmado por un test de inestabilidad cromosómica con diepoxibutano o mitomicina C - Edad> 1 año. - Al menos uno de los siguientes parámetros debe superar los valores indicados: Hemoglobina:8,0 g/dL; Número de neutrófilos: 750/mm3; Número de plaquetas: 30.000/mm3. - Índice de Lansky > 60%. - Fracción de eyección del ventrículo izquierdo >50%. - Otorgar consentimiento informado de acuerdo con la normativa legal vigente. - Las mujeres en edad fértil deberán obtener un resultado negativo en la prueba de embarazo en suero o en orina en la visita de selección , y aceptar el empleo de métodos anticonceptivos adecuados al menos desde los 14 días previos a la primera dosis del tratamiento movilizador hasta los 14 días siguientes a la última. |
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E.4 | Principal exclusion criteria |
- Evidence of myelodysplastic syndromes or leukemia, or cytogenetic abnormalities predicted of these syndromes in bone marrow aspiration. Cytogenetic analyses performed 2 months before starting study are accepted - Patients with active infection process or any other underlaying severe medical process - Severe Functional alteration of organs (hepatic, renal, respiratory)(?3), according to National Cancer Institute (NCI CTCAE v3) criteria - Haematopoietic transplant - Any disease or concomitant process that is not compatible with the study as per investigator opinion - Patients not elegible because of an psico-social evaluation - Patients that received transfusional support during the last 3 months. - Pregnant or breastfeeding women |
- Evidencias de síndrome mielodisplásico o leucemia, o anomalías citogenéticas predictivas de las mismas en aspirados de médula ósea Estudios citogenéticos realizados con dos meses de antelación se considerarán aceptables. - Pacientes con proceso infeccioso activo u otro estado médico subyacente grave. - Alteración funcional de órganos (hepática, renal, respiratorio) grave (?3),según los criterios del National Cancer Institute (NCI CTCAE v3). - Haber recibido trasplante hematopoyético. - Toda enfermedad o proceso concomitante que, en opinión del investigador, incapacite al sujeto para su participación en el estudio. - Pacientes que tras una evaluación psico-social se censuran como no aptos para el procedimiento. - Haber recibido soporte transfusional en los tres meses previos. - Mujeres embarazadas o en período de lactancia |
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E.5 End points |
E.5.1 | Primary end point(s) |
Toxicity of the mobilization procedure according to National Cancer Institute (CTC NCI, versión 3.0) |
Toxicidad del protocolo de movilización según los criterios comunes de toxicidad del National Cancer Institute (CTC NCI, versión 3.0) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
It is anticipated that the patient will receive the medical discharged at the end of the last apheresis. Once the patient is given a medical discharge, hematologic controls are performed at 2 weeks after the last apheresis (in the center where the collection was made), at 2 months, at 6 months and 9 months (in the center of patient referral if your physician is a research trial, or of the collection).
At a year (± 30 days) after the last apheresis, a complete physical examination, blood cell count, basic biochemistry and bone marrow aspirate will be done to the patient in order to control their general health status. |
Se prevé que el paciente será dado de alta al finalizar la última aféresis. Una vez dado el paciente de alta médica, se realizarán controles hematológicos a las 2 semanas de la última aféresis (en el centro donde se realizó la colecta), a los 2 meses, a los 6 meses y a los 9 meses (en el centro de referencia del paciente si su médico es investigador del ensayo, o en el de la colecta).
Al año (±30 dias) de realizada la última aféresis, se realizará un examen físico completo, recuento celular sanguíneo, bioquímica básica y un aspirado de la médula ósea del paciente para control. |
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E.5.2 | Secondary end point(s) |
- The effectiveness of the mobilization protocol will be determined by the percentage of patients who achieve peripheral blood counts exceeding 5 CD34+ cells /microliter. - The effectiveness of the CD34+ cell collection protocol will be determined by the percentage of patients who reach at least one million CD34 + cells per kilogram of body weight projected to 5 years after the mobilization process. - The effectiveness of the of CD34+ cell selection process will be determined by the proportion of immunoselected samples where the recovery of CD34 + cells is at least 50%, and where the final percentage of CD34+ cells is at least 50%. - The effectiveness of the procedure will be determined by the percentage of patients who reach at least one million CD34 + cells per kilo of weight projected to 5 years after the immunomagnetic selection process of all the collected cells. |
- Se determinará la eficacia de la movilización por el porcentaje de pacientes que alcancen en sangre periférica recuentos superiores a 5 células CD34+/microlitro. - Se determinará la eficacia de la recolección de células CD34+ por el porcentaje de pacientes que alcancen tras las aféresis más de un millón de células CD34+ por kilo de peso proyectado a 5 años tras la movilización. - Se determinará la eficacia de la selección de células CD34+ del producto obtenido tras aféresis, por el porcentaje de muestras en donde la recuperación de células CD34+ sea superior al 50%, y por el porcentaje final de células CD34+. -Se determinará la eficacia del procedimiento global por el porcentaje de pacientes que alcancen más de un millón de células CD34+ por kilo de peso proyectado a 5 años, tras la selección inmunomagnética de todas las aféresis realizadas. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Última aferesis |
Last apheresis |
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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) | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 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
|
Patients will be excluded or abandon their participation in the study for any of the following reasons: - Withdrawal of consent by the patient. - Evidence of disease progression. - Development of unacceptable toxicity in the investigator's opinion. - If it is consider relevant to the patient a change in treatment due to loss of clinical benefit, at the discretion of the investigator |
Los pacientes serán excluidos ó abandonarán su participación en el estudio por cualquiera de las siguientes razones: - Retirada del consentimiento por parte del paciente. - Evidencia de progresión de la enfermedad. - Desarrollo de toxicidad inaceptable a juicio del investigador. - Si se considera de interés para el paciente un cambio en el tratamiento por pérdida del beneficio clínico, según el criterio del investigador. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
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 |