E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Myeloid Leukemia (CML) |
Leucemia Mieloide Crónica (LMC) |
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E.1.1.1 | Medical condition in easily understood language |
CML is a type of Philadelphia Chromosome positive leukaemia resulting due to changes in chromosomes. It is characterized by the uncontrolled growth of white blood cells. |
LMC es un tipo de leucemia de cromosoma Filadelfia positivo debido a un cambio en los cromosomas. Es caracterizada por un crecimiento incontrolado de globulos blancos. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009012 |
E.1.2 | Term | Chronic myelogenous leukemia |
E.1.2 | System Organ Class | 100000004864 |
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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 |
? To allow long term bosutinib treatment in subjects with chronic or advanced phases Ph+ CML who received bosutinib in a previous Pfizer sponsored CML study (ie, studies B1871006 and B1871008) and who have the potential, as judged by the investigator, to derive clinical benefit from continued treatment with bosutinib; ? To collect long term safety and efficacy data for bosutinib; ? To assess the duration of clinical benefit for Ph+ CML subjects treated with bosutinib; ? To fulfill the European Medicines Agency (EMA) post approval requirement for the collection and analysis of safety data about diarrhea incidence after switch from clinical study to commercial bosutinib formulation. |
?Permitir el tratamiento a largo plazo con bosutinib en pacientes con LMC Ph+ en fase crónica o avanzada que han recibido bosutinib en un estudio previo de LMC promovido por Pfizer (es decir, estudios B1871006 y B1871008) y que, en opinión del investigador, tienen posibilidades de obtener un beneficio clínico del tratamiento continuado con bosutinib. ?Recopilar los datos de seguridad y eficacia a largo plazo para bosutinib. ?Evaluar la duración del efecto clínico beneficioso en los pacientes con LMC Ph+ tratados con bosutinib. ?Cumplir con el requisito posterior a la autorización por parte de la Agencia Europea del Medicamento (EMA) para la recopilación y el análisis de los datos de seguridad sobre la incidencia de diarrea tras el paso desde la formulación de bosutinib usada en el estudio clínico a la comercial. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study. 2. Previous enrollment in the bosutinib arm of one of the two Pfizer parent studies: B1871006 or B1871008. This includes: a. Subjects still receiving bosutinib in either study B1871006 or B1871008; b. Subjects who have discontinued bosutinib but are still in the long term follow up phase of the study B1871006 or B1871008; c. Subjects from study B1871006 who have discontinued bosutinib and have already completed the long term follow up period. 3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 4. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 30 days after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. |
Los pacientes deben cumplir todos los criterios de inclusión siguientes para ser aptos para participar en el estudio: 1.Prueba de un documento de consentimiento informado, firmado y fechado personalmente, que indique que se ha informado al paciente (o a su representante legal) de todos los aspectos pertinentes del estudio. 2.Inclusión previa en el brazo de bosutinib de uno de los dos estudios originales de Pfizer: B1871006 o B1871008. Esto incluye: a.Pacientes que todavía reciben bosutinib en el estudio B1871006 o en el B1871008. b.Pacientes que han suspendido el tratamiento con bosutinib pero todavía continúan en la fase de seguimiento a largo plazo del estudio B1871006 o el B1871008. c.Pacientes del estudio B1871006 que han suspendido el tratamiento de bosutinib y ya han completado el periodo de seguimiento a largo plazo. 3.Los pacientes deben estar dispuestos a y ser capaces de cumplir las visitas programadas, el plan de tratamiento, las pruebas analíticas y otros procedimientos del estudio. 4.Los pacientes de sexo masculino y femenino en edad fértil deben acceder a utilizar un método anticonceptivo de eficacia elevada durante todo el estudio y durante, al menos, 30 días después de la última dosis del tratamiento asignado. Se considera que un paciente está en edad fértil si, a juicio del investigador, está capacitado biológicamente para tener hijos y es sexualmente activo. |
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E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study: 1. Participation in other studies involving investigational drug(s) (Phases 1 to 4) while subject in the active treatment phase of the current study. 2. Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the trial. 3. Other severe acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 4. Pregnant females; breastfeeding females; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 30 days after last dose of investigational product. |
Los pacientes que presenten cualquiera de las siguientes características no serán incluidos en el estudio: 1.Participación en otros estudios que impliquen el uso de fármacos en investigación (fases I a IV) mientras que el paciente se encuentre en la fase de tratamiento activo del presente estudio. 2.Pacientes que sean miembros del personal del centro de investigación directamente implicados en la realización del ensayo, así como sus familiares, miembros del personal del centro supervisados de alguna otra manera por el investigador o empleados de Pfizer directamente implicados en la realización del ensayo. 3.Otras enfermedades de grado intenso, agudas o crónicas, médicas o psiquiátricas, incluidos el comportamiento o las ideas suicidas recientes (en el último año) o activas, así como las anomalías analíticas que puedan aumentar el riesgo asociado con la participación en el estudio o con la administración del producto experimental, o que puedan interferir en la interpretación de los resultados del estudio y, a juicio del investigador, hagan que el paciente no sea apto para incorporarse a este estudio. 4.Mujeres embarazadas; mujeres en periodo de lactancia; hombres y mujeres con capacidad para concebir que no utilicen anticonceptivos de alta eficacia o no estén de acuerdo en continuar con los anticonceptivos de alta eficacia durante al menos 30 días tras la última administración de la dosis del producto en investigación. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The objective of the study is to provide long term access to bosutinib treatment and assess long term safety, tolerability and duration of clinical benefit, without any formal hypothesis testing; therefore, there is no formal primary endpoint. In addition, study endpoints to be reported and data to be collected, specifically efficacy data, are planned to be different in the first line CP subjects relative to the later line and advanced subjects.
For all subjects regardless of the line of treatment: ? Long term safety of bosutinib, including type, incidence, severity, timing, seriousness and relatedness of AEs and laboratory abnormalities as well as reason of treatment discontinuation. A special focus will be made on diarrhea in order to satisfy the EMA post commitment request; ? BCR ABL mutations present at the time subjects discontinue bosutinib; ? Overall survival (OS),
For 2nd or later line subjects coming from study B1871006: as long as subjects are on treatment with bosutinib, the following efficacy endpoints will be assessed: ? Duration of hematologic and cytogenetic responses; ? Progression free survival; ? Time to transformation to accelerated or blast phase. |
El objetivo del estudio es proporcionar acceso a largo plazo al tratamiento con bosutinib, y evaluar la seguridad, la tolerabilidad y la duración del beneficio clínico a largo plazo, sin ninguna prueba de hipótesis formal; por lo tanto, no hay un criterio de valoración principal formal. Además, se espera que los criterios de valoración del estudio que hay que presentar y los datos que hay que recopilar, en concreto los datos sobre la eficacia, sean diferentes en los pacientes en FCr con un tratamiento de primera línea respecto a los pacientes avanzados y con un tratamiento de líneas posteriores. Para todos los pacientes, independientemente de la línea de tratamiento: ?Seguridad a largo plazo de bosutinib, incluido el tipo, la incidencia, la intensidad, el momento de aparición, la gravedad y la relación causal de los AA y las anomalías de laboratorio, así como el motivo para suspender el tratamiento. Se prestará especial atención a la diarrea para satisfacer el requisito de la EMA posterior a la autorización. ?Mutaciones de BCR-ABL presentes en el momento en que los pacientes suspenden el tratamiento de bosutinib. ?Supervivencia global (SG). Para los pacientes en tratamiento de 2a línea o posteriores que provienen del estudio B1871006: mientras los pacientes se encuentren bajo tratamiento con bosutinib, se evaluarán los siguientes criterios de valoración de la eficacia: ?duración de las respuestas hematológica y citogenética; ?supervivencia sin progresión; ?tiempo transcurrido hasta la evolución a la fase de aceleración o blástica. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For CML 1st line subjects coming from B1871008: ? AEs collected at ? 28 days from last dose on parent study, at site visit at month 3, every 12 months, at phone calls every 3 months, and at ? 28 days after last dose of bosutinib. For CML 2nd and later line subjects coming from B1871006: ? AEs collected at ? 28 days from last dose on parent study, at site visit at month 3, at every 6 months, at phone calls every 3 months, and at ? 28 days after last dose of bosutinib. For all subjects: ? Diarrhea information collected at ? 28 days from last dose on parent study and at month 3 site visit. ? BCR ABL mutation analysis at ? 28 days after last dose of bosutinib. ? Survival follow-up at every 3 months from last dose of bosutinib for up to 10 years from first dose (including parent study). |
Puffff |
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E.5.2 | Secondary end point(s) |
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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 | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Extension de estudio - no aplica la phase |
extension study - phase is N/A |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Chile |
China |
Colombia |
Finland |
France |
Germany |
Hong Kong |
Hungary |
India |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lithuania |
Mexico |
Netherlands |
Peru |
Poland |
Russian Federation |
Singapore |
South Africa |
Spain |
Thailand |
Turkey |
Ukraine |
United Kingdom |
United States |
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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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LVLS (please refer to protocol) |
Ultima Visita del Ultimo Paciente (Por favor, ver el protocolo) |
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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 | 7 |
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 | 7 |
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 |