E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Myeloid Leukemia in Chronic Phase |
Leucemia Mieloide Crónica en Fase Crónica |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
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 compare the efficacy of ponatinib with imatinib as measured by major molecular response (MMR) rate at 12 months (1 month or cycle = 28 days) |
Comparar la eficacia de Ponatinib con Imatinib medida a través de la tasa de respuesta molecular mayor (RMM) a los 12 meses (1 mes o ciclo = 28 días). |
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E.2.2 | Secondary objectives of the trial |
? To compare, according to treatment with ponatinib versus imatinib, MMR rate at 5 years ?To compare the proportion of patients achieving a ratio of <10% BCR-ABL to ABL transcript levels at 3 months, as measured by the international scale (<10% BCR-ABLIS), in patients administered ponatinib versus those administered imatinib ? To compare, according to treatment with ponatinib versus imatinib, the complete cytogenetic response (CCyR) rate at 12 months ? To compare, according to treatment with ponatinib versus imatinib, progression-free survival and overall survival Other secondary and exploratory study objectives as listed in the protocol |
-Comparar, según el tratamiento con Ponatinib frente a Imatinib, la tasa de RMM a los 5 años. -Comparar el porcentaje de pacientes que logran un cociente < 10% en los niveles de transcriptos de BCR-ABL con respecto a ABL a los 3 meses, medida mediante la escala internacional (BCR-ABLIS < 10%) en los pacientes tratados con Ponatinib frente a los tratados con Imatinib. -Comparar, según el tratamiento con Ponatinib frente a Imatinib, la respuesta citogenética completa (RCiC) a los 12 meses. -Comparar, según el tratamiento con Ponatinib frente a Imatinib, la supervivencia sin progresión y la supervivencia global. Otros objetivos secundarios y exploratorios se presentan en el protocolo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients ?18 years old 2. CP-CML within 6 months of diagnosis 3. Cytogenetic assessment must demonstrate the BCR-ABL fusion by presence of the t(9;22) Philadelphia chromosome 4. ECOG Performance Status of 0, 1, or 2 5. Adequate hepatic function as defined in the protocol 6. Adequate renal function as defined in the protocol 7. Adequate pancreatic function as defined in the protocol 8. For females of childbearing potential, a negative pregnancy test must be documented prior to randomization 9. Female and male patients who are of childbearing potential must agree to use an effective form of contraception with their sexual partners from randomization through 30 days after the end of treatment 10. Provide written informed consent 11. Willingness and ability to comply with scheduled visits and study procedures |
1. Pacientes de ambos sexos ? 18 años de edad 2. LMC- FC en los 6 meses posteriores al diagnóstico 3. La evaluación de marcadores citogenéticos debe demostrar la fusión de BCR- ABL mediante presencia del cromosoma Filadelfia t(9;22) 4. Estado funcional según la escala ECOG de 0, 1 o 2 5. Función hepática adecuada, tal como la define el protocolo 6. Función renal adecuada, tal como la define el protocolo 7. Función pancreática adecuada, tal como la define el protocolo 8. En mujeres en edad fértil debe confirmarse una prueba de embarazo negativa antes de la aleatorización 9. Los pacientes de ambos sexos en edad fértil deben aceptar usar un método anticonceptivo eficaz con sus parejas sexuales desde la aleatorización hasta 30 días después del final del tratamiento. 10. Obtención del consentimiento informado por escrito 11. Disposición y capacidad para cumplir con las visitas programadas y los procedimientos del estudio |
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E.4 | Principal exclusion criteria |
1. Received prior imatinib therapy 2. Received prior dasatinib therapy 3. Received prior nilotinib therapy 4. Received, for CML, any other systemic anticancer therapy, experimental therapy, or radiation therapy with the exception of anagrelide or hydroxyurea 5. Major surgery within 28 days prior to initiating therapy 6. History of bleeding disorder unrelated to CML 7. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis 8. History of alcohol abuse 9. Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL) 10. Significant uncontrolled or active cardiovascular disease 11. Uncontrolled hypertension (diastolic blood pressure >100 mm Hg; systolic >150 mm Hg) 12. Taking medications that are known to be associated with Torsades de Pointes (Appendix A) 13. Ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection 14. Known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history 15. Pregnant or breastfeeding 16. Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drugs 17. Diagnosed with or received anticancer therapy for another primary malignancy within 3 years prior to entry (except for non-melanoma skin cancer or cervical cancer in situ) 18. Any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the drug |
1. Haber recibido previamente tratamiento con Imatinib 2. Haber recibido previamente tratamiento con dasatinib 3. Haber recibido previamente tratamiento con nilotinib 4. Haber recibido, para la LMC, cualquier otro tratamiento antineoplásico sistémico, tratamiento experimental o radioterapia con la excepción de anagrelida o hidroxiurea 5. Cirugía mayor en los 28 días previos al inicio del tratamiento 6. Antecedentes de trastorno hemorrágico no relacionado con la LMC 7. Antecedentes de pancreatitis aguda en el año previo al estudio o antecedentes de pancreatitis crónica 8. Antecedentes de consumo de alcohol 9. Hipertrigliceridemia no controlada (triglicéridos > 450 mg/dl) 10. Enfermedad cardiovascular activa o no controlada significativa 11. Hipertensión no controlada (presión arterial diastólica > 100 mm Hg; presión arterial sistólica > 150 mm Hg) 12. Toma de medicamentos que se sabe que se asocian a Torsades de pointes (Anexo A) 13. Infección activa o en curso. La necesidad de antibióticos intravenosos (i.v.) se considera infección activa. 14. Antecedentes conocidos de virus de la inmunodeficiencia humana (VIH). Las pruebas no son necesarias en ausencia de antecedentes. 15. Embarazo o lactancia 16. Síndrome de malabsorción u otras enfermedades gastrointestinales que puedan afectar a la absorción oral de los fármacos del estudio 17. Diagnostico de otra neoplasia maligna primaria o haber recibido tratamiento antineoplásico para ella en los 3 años anteriores a la inclusión en el estudio (excepto para cáncer de piel no-melanoma o cáncer cervicouterino in situ) 18. Cualquier afección o enfermedad que, en opinión del investigador, pueda poner en peligro la seguridad del paciente o interferir en la evaluación del fármaco |
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E.5 End points |
E.5.1 | Primary end point(s) |
MMR rate at 12 months (1 month or cycle = 28 days) |
Tasa de RMM a los 12 meses (1 mes o ciclo = 28 días). |
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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) |
Key secondary endpoints: 1 MMR rate at 5 years 2 <10% BCR-ABLIS rate at 3 months 3 CCyR rate at 12 months 4 Progression-free survival 5 Overall survival Other Secondary Endpoints as listed in the protocol |
Principales criterios secundarios de valoración 1.Tasa de RMM a los 5 años 2.Tasa de BCR-ABLIS < 10% a los 3 meses 3.Tasa de RCiC a los 12 meses 4.Supervivencia sin progresión 5.Supervivencia global |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 MMR rate at 5 years 2 <10% BCR-ABLIS rate at 3 months 3 CCyR rate at 12 months |
1.Tasa de RMM a los 5 años 2.Tasa de BCR-ABLIS < 10% a los 3 meses 3.Tasa de RCiC a los 12 meses |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 82 |
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 |
Australia |
Austria |
Belgium |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hong Kong |
Ireland |
Israel |
Italy |
Korea, Republic of |
Netherlands |
New Zealand |
Norway |
Poland |
Portugal |
Singapore |
Slovakia |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
United States |
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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 |
Última visita del último paciente que entró en el estudio |
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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 | 10 |
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 | 10 |
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 |