E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Myeloid Leukemia (CML) with substained Complete Molecular Response (CMR) for at least 18 monthes. |
Leucemia Mieloide Crónica(CML) con Respuesta Molecolar Completa (CMR) mantenida durante al menos 18 meses |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Myeloid Leukemia (CML) asymptomatic and with no sign of disease by the most sensitive conventional hospital investigations. |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052065 |
E.1.2 | Term | Chronic phase chronic myeloid leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 assess the capability of the dPCR technique to predict the absence of disease relapses after imatinib discontinuation in CML patients with negative Q-RT-PCR results for longer than 18 months. |
Evaluar la capacidad de la técnica dPCR de predecir la ausencia de recaídas de la enfermedad tras la interrupción del tratamiento con imatinib en pacientes con LMC que tengan resultados negativos de Q-RT-PCR durante más de 18 meses. |
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E.2.2 | Secondary objectives of the trial |
1. To estimate relapse rate after imatinib discontinuation. 2. To characterize the performances of the dPCR technique. 3. To quantify the maintenance of the molecular remission, after imatinib discontinuation, in CML patients with negative Q-RT-PCR for longer than 18 months. 4. To evaluate the impact of imatinib treatment (discontinuation and resumption) on quality of life. 5. To assess the timing of recurrence. 6. To quantify the occurrence of progression/resistance in patients who relapse after imatinib resumption. 7. To evaluate whether survival of patients dPCR negative and relapse free at 36 months is comparable to the one of normal population. 8. To evaluate whether survival of relapsing patients is comparable to the survival of the non relapsing ones. |
1. Estimar la tasa de recaída después de la interrupción del tratamiento con imatinib. 2. Caracterizar el rendimiento de la técnica dPCR. 3. Cuantificar el mantenimiento de la remisión molecular, después de la interrupción del tratamiento con imatinib, en pacientes con LMC que tengan resultados negativos de Q-RT-PCR durante más de 18 meses. 4. Evaluar el impacto del tratamiento (suspensión y reanudación) con imatinib en la calidad de vida. 5. Evaluar el tiempo de recurrencia. 6. Cuantificar la incidencia de progresión/resistencia en pacientes que recaen tras la reanudación del tratamiento con imatinib. 7. Evaluar si la supervivencia de los pacientes con resultado dPCR negativo y sin recaída a los 36 meses es comparable con el de la población normal. 8. Evaluar si la supervivencia de los pacientes con recaída es comparable con la de los pacientes sin recaída |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated IRB/IEC-approved Informed Consent. 2. Age >/= 18 years. 3. Male or female patients with CML diagnosed in chronic phase and who have been treated for more than 2 consecutive years with imatinib therapy. 4. Sustained Complete Molecular Response (as defined by the treating center) for at least 18 months with imatinib treatment. 5. A minimum of 3 CMR determined by Q-RT-PCR analysis to support disease status, with the least one performed within 3 calendar months prior to enrollment date. 6. Willingness and ability to comply with scheduled visits, laboratory tests and other study procedures. |
1. Firmar y fechar el Consentimiento Informado aprobado por el Comité Ético y de Investigación Clínica. 2. Edad >/= 18 años. 3. Pacientes hombres o mujeres con LMC diagnosticada en fase crónica que hayan sido tratados con terapia con Imatinib durante más de dos años consecutivos. 4. CMR mantenida (tal como se define por el centro que lleva a cabo el tratamiento) durante al menos 18 meses con el tratamiento con Imatinib. 5. Un mínimo de 3 CMR determinadas por análisis con Q-RT-PCR como apoyo al estado de la enfermedad, con la última llevada en los 3 meses naturales previos a la fecha de inclusión. 6. Voluntad y capacidad para cumplir con las visitas programadas, las pruebas de laboratorio y otros procedimientos relacionados con el estudio. |
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E.4 | Principal exclusion criteria |
1. Allogenic hematopoietic stem cell transplantation. 2. Known active infections, including human immunodeficiency virus (HIV) positivity. 3. Current enrollment in another clinical trial. 4. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results. |
1. Transplante alogénico de células madre hematopoyéticas. 2. Infecciones activas conocidas, incluyendo ser positivo para el virus de la inmunodeficiencia humana (VIH). 3. Participación actual en otro ensayo clínico. 4. Cualquier otra condición médica o psiquiátrica severa, aguda o crónica o alteración de laboratorio que puedan aumentar el riesgo asociado a la participación del estudio o a la administración de medicamentos o que pueda interferir en la interpretación de los resultados del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The Negative Predicted Value Ratio (rNPV) of dPCR over Q-RT-PCR, i.e. the capability of the dPCR method to predict relapse-free patients relative to the standard method. NPV of each method will be computed as the number of patients who are negative according to either method at the time of imatinib discontinuation and remain relapse-free 36 months later over the total of negative patients according to either method, respectively. |
La relación de valor predictivo negativo (rNPV) de la dPCR frente a la Q-RT-PCR, p.e. La capacidad del método dPCR de predecir pacientes sin recaídas en relación con el método estándar. El NPV de cada método se calculará como el número de pacientes que son negativos para cada método en el momento de la interrupción del tratamiento con imatinib y que permanecen sin recaídas durante los 36 meses posteriores, frente al total de pacientes con resultado negativo según cada método, respectivamente. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 36 months. |
A los 36 meses |
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E.5.2 | Secondary end point(s) |
1. Rate of molecular and cytogenetic relapse after discontinuation of imatinib treatment out of total number of patients enrolled. 2. Rate of patients who are dPCR positive before discontinuation of imatinib and who do not relapse within the following 36 months (false positive) out of the total number of relapse-free patients at month 36. 3. Rate of patients who are dPCR negative before discontinuation of imatinib and who relapse (false negative) out of the total number of patients relapsing within the following 36 months. 4. Rate of patients maintaining dPCR negativity for 36 months over the patients who are Q-RT-PCR negative at the end of the interval. 5. Time to molecular relapse, both from the first PCR negative and from the discontinuation of imatinib to the time of loss of molecular response, respectively. 6. Overall survival. 7. Quality of Life, as measured by the Global Health Status/QOL and other subscales scores of EORTC-QLQ-C30 questionnaire. 8. Rate of patients progressing or developing resistance after imatinib resumption out of total number of patients enrolled. |
1. Tasa de recaída molecular y citogenética tras la interrupción del tratamiento con imatinib sobre el número total de pacientes incluídos. 2. Tasas de pacientes que tienen dPCR positiva antes de la interrupción del tratamiento con imatinib y que no recaen durante los 36 meses siguientes (falso positivo) sobre el número total de pacientes sin recaída en el mes 36. 3. Tasa de pacientes que tienen dPCR negativa antes de la interrupción del tratamiento con imatinib y que recaen (falso negativo) sobre el número total de pacientes que recaen durante los 36 meses siguientes. 4. Tasa de pacientes que mantienen resultados negativos de dPCR durante 36 meses, sobre los pacientes con resultados Q-RT-PCR negativos al final del intervalo. 5. Tiempo de recaída molecular, desde la primera PCR negativa y desde la interrupción del tratamiento con imatinib hasta el tiempo de pérdida de respuesta molecular, respectivamente. 6. Supervivencia global. 7. Calidad de vida, medida según el Estatus de Salud Global/QOL y otras puntuaciones de subescalas del cuestionario EORTC-QLQ-C30. 8. Tasa de pacientes que muestran progresión o desarrollan resistencia tras retomar el tratamiento con imatinib del total de pacientes incluídos. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All at 36 months, except for the overall survival (point 6) that will be evaluated at the end of the study. |
Todos a los 36 meses, excepto para los casos de supervivencia global (punto 6) que serán evaluados al finalizar el estudio |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Validation of a new analytical method, evaluation of the quality of life. |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
Canada |
Germany |
Israel |
Italy |
Spain |
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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 visit of the last patient, including follow-up. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 84 |
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 | 84 |
E.8.9.2 | In all countries concerned by the trial days | 0 |