E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse large B-cell lymphoma |
Linfoma difuso de linfocitos B |
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E.1.1.1 | Medical condition in easily understood language |
Diffuse large B-cell lymphoma |
Linfoma difuso de linfocitos B |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012818 |
E.1.2 | Term | Diffuse large B-cell lymphoma |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of INCB050465 in terms of objective response rate (ORR) in subjects with relapsed or refractory DLBCL who were not previously treated with a BTK inhibitor (group A). |
Evaluar la eficacia de INCB050465 en términos de tasa de respuesta objetiva (TRO) en sujetos con linfoma macrocítico difuso de linfocitos B (LMDLB) recidivante o resistente al tratamiento en el grupo A. |
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E.2.2 | Secondary objectives of the trial |
• To assess the duration of response (DOR) in subjects who were not previously treated with a BTK inhibitor (group A) • To assess progression-free survival (PFS) in group A • To assess overall survival (OS) in group A • To characterize the safety of INCB050465 |
Evaluar la duración de la respuesta (DdR) en el grupo A. Evaluar la supervivencia sin progresión (SSP) en el grupo A. Evaluar la supervivencia general (SG) en el grupo A. Caracterizar la seguridad de INCB050465 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Men and women, aged 18 years or older. • Relapsed or refractory DLBCL, which has been histologically documented, defined as having received at least 2 but no more than 5 prior treatment regimens (eg, an anti-CD20 antibody, an anti-CD20 antibody with or without chemotherapy, or chemotherapy alone) and ineligible for high-dose chemotherapy supported by autologous stem cell transplant. • Must have ≥ 1 measurable (≥ 2 cm in longest dimension) or ≥ 1 measurable extranodal lesion (> 1 cm in longest dimension) lesion on computed tomography (CT) scan or magnetic resonance imaging (MRI). • Subjects must be willing to undergo an incisional or excisional lymph node biopsy of accessible adenopathy or provide the most recent, available archived tumor biopsy. • Eastern Cooperative Oncology Group performance status 0 to 2. |
- Hombres y mujeres de 18 años de edad o mayores (salvo en Corea del Sur, 19 años de edad o mayores). - LMDLB recidivante o resistente al tratamiento, que haya sido documentado histológicamente, definido como haber recibido al menos 2 pero no más de 5 pautas de tratamiento previas (p. ej., un anticuerpo anti-CD20, un anticuerpo anti-CD20 con o sin quimioterapia, o solo quimioterapia) y no ser aptos para quimioterapia en dosis altas complementada con autotrasplante de células madre. -Deben presentar ≥1 lesión medible (≥2 cm en su dimensión más larga) o ≥1 lesión extraganglionar medible (>1 cm en su dimensión más larga) en una tomografía axial computarizada (TAC) o resonancia magnética (RM). -Los sujetos deben estar dispuestos a someterse a una biopsia por incisión o escisión de un ganglio linfático de la adenopatía accesible o proporcionar la biopsia tumoral de archivo más reciente disponible. -Estado general según el Grupo Oncológico Cooperativo del Este de entre 0 y 2. |
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E.4 | Principal exclusion criteria |
• Primary mediastinal (thymic) large B-cell lymphoma. • Known brain or central nervous system metastases or history of uncontrolled seizures. • Allogeneic stem cell transplant within the last 6 months, or active graft versus host disease following allogeneic transplant, or autologous stem cell transplant within the last 3 months. • Use or expected use during the study of any prohibited medications, including potent cytochrome P450 3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug. • Prior treatment with the following: − Group A: Prior treatment with a selective phosphatidylinositol 3-kinase (PI3K) δ inhibitor (eg, idelalisib), a pan-PI3K inhibitor, or a BTK inhibitor (eg, ibrutinib). − Group B: Prior treatment with a selective PI3Kδ inhibitor (eg, idelalisib) or a pan-PI3K inhibitor. |
-Linfoma macrocítico de linfocitos B mediastínico (tímico) primario. -Metástasis conocidas cerebrales o en el sistema nervioso central o antecedentes de convulsiones incontroladas. -Alotrasplante de células madre en los últimos 6 meses o enfermedad de injerto contra huésped activa después del alotrasplante o autotrasplante de células madre en los últimos 3 meses. -Uso o uso previsto durante el estudio de cualquier medicamento prohibido, incluyendo inhibidores o inductores potentes del citocromo P450 3A4 en un plazo de 14 días o 5 semividas (lo que sea más prolongado) antes de la primera dosis del fármaco del estudio. -Tratamiento previo con los siguientes: Grupo A: tratamiento previo con un inhibidor selectivo de la fosfatidilinositol 3-cinasa (PI3K) δ (p. ej., idelalisib), un inhibidor de todas las PI3K o un inhibidor de BTK (p. ej., ibrutinib). Grupo B: tratamiento previo con un inhibidor selectivo de PI3Kδ (p. ej., idelalisib) o un inhibidor de todas las PI3K. |
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E.5 End points |
E.5.1 | Primary end point(s) |
ORR in Group A, defined as the percentage of subjects with a complete response/complete metabolic response (CR/CMR) or partial response/partial metabolic response (PR/PMR) as defined by revised response criteria for lymphomas (Cheson et al 2014), as determined by an Independent Review Committee. |
Tasa de respuesta objetiva en el Grupo A, definida como el porcentaje de sujetos con una respuesta completa/respuesta metabólica completa (RC/RMC) o respuesta parcial/respuesta metabólica parcial (RP/RMP) según la definición de los criterios revisados de respuesta en linfomas, según determine un comité de revisión independiente (CRI). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 2 years after the first dose is administered to the last subject enrolled |
Hasta 2 años después de administrar la primera dosis al último sujeto reclutado |
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E.5.2 | Secondary end point(s) |
• DOR in Group A, defined as the time from first documented evidence of CR/CMR or PR/PMR until disease progression or death from any cause among subjects who achieve an objective response, as determined by radiographic disease assessment provided by an IRC. • PFS in Group A, defined as the time from the date of the first dose of study drug until the earliest date of disease progression, as determined by radiographic disease assessment provided by an IRC, or death from any cause. • OS in Group A, defined as the time from the date of the first dose of study drug until death by any cause. • Safety as measured by clinical assessments, including vital signs and physical examinations, 12-lead electrocardiograms (ECG), chemistry and hematology laboratory values, and adverse events (AEs). |
Duración de la respuesta en el Grupo A, definida como el tiempo transcurrido desde la primera evidencia documentada de RC/RMC o RP/RMP hasta la progresión de la enfermedad o la muerte por cualquier causa en los sujetos que alcancen una respuesta objetiva, según se determine mediante una evaluación radiográfica de la enfermedad proporcionada por un CRI. Supervivencia sin progresión en el Grupo A, definida como el tiempo transcurrido desde la fecha de la primera dosis del fármaco del estudio hasta la fecha más temprana de progresión de la enfermedad, según se determine mediante una evaluación radiográfica de la enfermedad proporcionada por un CRI, o la muerte por cualquier causa. SG en el Grupo A, definida como el tiempo transcurrido desde la fecha de la primera dosis del fármaco del estudio hasta la muerte por cualquier causa. Seguridad, según se determine mediante evaluaciones clínicas, que incluyen constantes vitales y exploraciones físicas, electrocardiogramas (ECG) de 12 derivaciones, valores analíticos de bioquímica y hematología, y acontecimientos adversos (AA). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 2 years after the first dose is administered to the last subject enrolled |
Hasta 2 años después de administrar la primera dosis al último sujeto reclutado |
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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) | 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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
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 | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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 |
Canada |
Korea, Republic of |
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
|
The study will continue up to 2 years after the first dose of study treatment is administered to the last subject enrolled, at which point the study will be closed. |
El estudio continuará hasta 2 años después de que se administre la primera dosis de tratamiento del estudio al último sujeto reclutado, momento en el que el estudio se cerrará. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 1 |