E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Lymphocytic Leukemia |
Leucemia Linfocítica Crónica |
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E.1.1.1 | Medical condition in easily understood language |
Chronic lymphocytic leukemia (CLL) is a type of cancer affecting the blood and the bone marrow. |
Leucemia Linfocítica Crónica (LLC) es un tipo de cáncer que afecta a la sangre y a la médula ósea. |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008958 |
E.1.2 | Term | Chronic lymphocytic 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 |
The primary objective of this study to evaluate the efficacy of venetoclax monotherapy in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) including those with the 17p deletion or TP53 gene mutations or in CLL subjects who have received prior B-Cell receptor inhibitor (BCRi) therapy. |
El objetivo principal del estudio es evaluar la eficacia de venetoclax en monoterapia en sujetos con leucemia linfocítica crónica (LLC) recidivante o resistente, incluidos aquellos con deleción 17p o mutación del gen TP53 o aquellos con intolerancia o resistencia al tratamiento con inhibidores del receptor de los linfocitos B (IRLB). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate other efficacy parameters including the overall response rate (ORR), duration of overall response (DoR), time to progression (TTP), progression-free survival (PFS), overall survival (OS), Complete Remission rate in BCRi treated subjects and both the level of Minimal Residual Disease (MRD) and the rate of MRD negativity. |
Los objetivos secundarios son evaluar otros parámetros de eficacia, como la tasa de respuesta global (TRG), la duración de la respuesta global (DRG), el tiempo hasta la progresión (THP), la supervivencia Libre de Progresión (SLP), la supervivencia global (SG), la tasa de remisión completa en los sujetos tratados con IRLB, el grado de enfermedad residual mínima (ERM) y la tasa de negatividad para la ERM en sangre periférica. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years. 2. Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2. 3. Subject has relapsed/refractory disease (received at least one prior therapy). 4. Diagnosis of CLL that meets published 2008 Modified International Workshop on CLL National Cancer Institute – Working Group (IWCLL NCI-WG) Guidelines and: • has an indication for treatment according to the 2008 Modified IWCLL NCI-WG Guidelines • has clinically measurable disease (lymphocytosis > 5 × 10^9/L and/or palpable and measurable nodes by physical exam and/or organomegaly assessed by physical exam) In addition, patients: • may harbor 17p deletion or TP53 mutation, assessed by a local laboratory in bone marrow or peripheral blood AND / OR • may have been previously treated with a B-cell receptor inhibitor. 5. Adequate bone marrow function as follows: • platelets ≥ 25,000/mm^3 without any of the following: o transfusion support within 14 days of Screening o evidence of mucosal bleeding o known history of major bleeding episode within 3 months of Screening • hemoglobin ≥ 8.0 g/dL |
1. Edad ≥18 años 2. Estado funcional ≤2 del Eastern Cooperative Oncology Group (ECOG) 3. Enfermedad recidivante o resistente (el sujeto ha recibido al menos un tratamiento previo) 4. Diagnóstico de LLC que cumpla las directrices modificadas del IWCLL NCI-WG publicadas en 2008 y: - Presente una indicación de tratamiento según los criterios modificados del IWCLL NCI-WG de 2008 - Constituya una enfermedad clínicamente medible (linfocitosis > 5 × 109/l, ganglios linfáticos palpables y medibles mediante exploración física y/o organomegalia identificada mediante exploración física, o todos ellos). Además, los pacientes: - Pueden presentar deleción 17p o mutación del gen TP53, identificadas mediante análisis de médula ósea o sangre periférica del laboratorio local Y/O - Pueden haber recibido con anterioridad un inhibidor del receptor de los linfocitos B. 5. Función medular adecuada, definida por lo siguiente: - Plaquetas ≥25.000/m3 en ausencia de: O Transfusión dentro de los 14 días a la selección. O Signos de hemorragia de las mucosas. O Antecedentes de episodio hemorrágico grave en los tres meses anteriores a la selección. - Hemoglobina ≥ 8.0 g/dL. |
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E.4 | Principal exclusion criteria |
1. Subject has developed Richter's transformation or Prolymphocytic leukemia (PLL) 2. Subject has previously received venetoclax. 3. History of active malignancies other than CLL within the past 2 years prior to first dose of venetoclax, with the exception of: • adequately treated in situ carcinoma of the cervix uteri • adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin • previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. 4. Active and uncontrolled autoimmune cytopenias (within 2 weeks prior to Screening), including autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP), despite low dose corticosteroids. 5. Prior allogeneic stem cell transplant. |
1. Haber sufrido una transformación de Richter o leucemia prolinfocítica (LPL) 2. Sujetos que hayan recibido venetoclax con anterioridad. 3. Antecedentes de neoplasias malignas activas distintas de la LLC en los dos años previos a la primera dosis con venetoclax, con las siguientes excepciones: - Carcinoma in situ de cérvix uterino convenientemente tratado. - Carcinoma basocelular o carcinoma de células escamosas localizado de la piel convenientemente tratado. - Neoplasia maligna localizada y extirpada quirúrgicamente (o tratada con otras modalidades) con fines curativos. 4. Citopenia autoinmunitaria activa y no controlada (en las 2 semanas anteriores a la selección), incluidas la anemia hemolítica autoinmune (AHAI) y la púrpura trombocitopénica idiopática (PTI), a pesar del tratamiento con corticoesteroides en dosis bajas. 5. Antecedentes de alotransplante de células progenitoras. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be complete remission rate (CR + CRi) defined as the proportion of subjects achieving a CR or CRi as their best response (per the investigator assessment) based on IWCLL NCI-WG criteria. |
El criterio principal de valoración de la eficacia será la tasa de remisión completa (RC + RCi), definida como el porcentaje de sujetos que logren la RC o la RCi como mejor respuesta (según la evaluación efectuada por el investigador) conforme a los criterios del IWCLL NCI-WG. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The date the last enrolled subject has completed their Week 48 disease assessment, or after all enrolled subjects have discontinued venetoclax, whichever is earlier, will be defined as the data "cutoff" date for the efficacy analyses. |
La fecha de «corte» de los datos para los análisis de la eficacia será la fecha en que el último sujeto inscrito haya completado las evaluaciones de la visita 48 o después de que todos los sujetos incluidos hayan dejado de recibir venetoclax, lo que suceda antes. |
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E.5.2 | Secondary end point(s) |
Key secondary efficacy endpoints: Overall response rate, duration of response, time to progression, progression-free survival, overall survival, complete remission rate in B-Cell receptor inhibitor treated subjects and both the level of Minimal Residual Disease (MRD) and the rate of MRD negativity. |
Criterios de valoración secundarios de la eficacia La tasa de respuesta global, la duración de la respuesta, el tiempo hasta la progresión, la supervivencia libre de progresión, la supervivencia global, la tasa de remisión completa en los sujetos previamente tratados con inhibidores de receptores de las células B y el grado de Enfermedad Residual Mínima y la tasa de negatividad para la Enfermedad Residual Mínima. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The date the last enrolled subjects has completed their Week 48 disease assessment, or after all enrolled subjects have discontinued venetoclax, whichever is earlier, will be defined as the data "cutoff" date for the efficacy analyses. |
La fecha de «corte» de los datos para los análisis de la eficacia será la fecha en que el último sujeto inscrito haya completado las evaluaciones de la visita 48 o después de que todos los sujetos inscritos hayan dejado de recibir venetoclax, lo que suceda antes. |
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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 | Yes |
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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Austria |
Belgium |
Canada |
Denmark |
Finland |
France |
Germany |
Greece |
Ireland |
Israel |
Italy |
Netherlands |
Norway |
Portugal |
Puerto Rico |
Spain |
Sweden |
Switzerland |
Turkey |
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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The end-of-study is defined as the date of the last subject's last visit or date of the last follow up contact, whichever is later. |
El final del estudio se define como la fecha de la última visita del último paciente o la fecha del último contacto de seguimiento, lo que ocurra antes. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |