E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Indolent Non-Hodgkin Lymphoma |
Linfoma No-Hodgkin Indolente |
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E.1.1.1 | Medical condition in easily understood language |
Indolent Non-Hodgkin Lymphoma |
Linfoma No-Hodgkin Indolente |
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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 | HLT |
E.1.2 | Classification code | 10029621 |
E.1.2 | Term | Non-Hodgkin's lymphomas unspecified histology indolent |
E.1.2 | System Organ Class | 100000004851 |
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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 |
Evaluate the efficacy of DBR vs PBR in subjects with previously-treated iNHL |
Evaluar la eficacia de DBR frente a PBR en sujetos con iNHL previamente tratado. |
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E.2.2 | Secondary objectives of the trial |
- Evaluate the safety of DBR and PBR in subjects with previously-treated iNHL - Characterize the pharmacokinetics (PK) of duvelisib when administered with bendamustine and rituximab (BR) in subjects with previously-treated iNHL Exploratory Objectives: - Evaluate if biomarkers can predict clinical efficacy and/or safety of DBR vs PBR in subjects with previously-treated iNHL - Evaluate Quality of Life (QoL) outcomes in subjects with previously-treated iNHL |
- Evaluar la seguridad de DBR y PBR en sujetos con iNHL previamente tratado. - Caracterizar la farmacocinética (FC) de duvelisib al administrarse con bendamustina y rituximab (BR) en sujetos con iNHL previamente tratado. Objetivos exploratorios: - Evaluar si los biomarcadores pueden predecir la eficacia clínica y/o la seguridad de DBR frente a PBR en sujetos con iNHL previamente tratado. - Evaluar los resultados en cuanto a la calidad de vida (CdV) en sujetos con iNHL previamente tratado. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.?18 years of age 2. Diagnosis of iNHL with one of the following histologic sub-types and grade: - Follicular lymphoma (FL)Grade 1, 2, or 3a - Small lymphocytic lymphoma (SLL) - Marginal zone lymphoma (MZL)( splenic, nodal, or extranodal) 3. Have received the following systemic treatments for iNHL: - an anti-CD20 antibody; and - chemotherapy 4. At least 1 measurable disease lesion > 1.5 cm in at least one dimension by computed tomography (CT)/CT-PET or magnetic resonance imaging (MRI) 5. Eastern Cooperative Oncology Group (ECOG) performance status ?2 (corresponds to Karnofsky Performance Status [(KPS) ?60%]) For full inclusion criteria list, refer to protocol. |
1.?18 años de edad 2. Diagnóstico de iNHL con uno de los siguientes subtipos histológicos y grado: -Linfoma Folicular (FL): Grado 1, 2 o 3a -Linfoma Linfocítico pequeño (SLL) -Linfoma de zona marginal (MZL): esplénico, ganglionar o extraganglionar 3. Haber recibido los siguientes tratamientos sistémicos para el iNHL: -un anticuerpo anti-CD20; y -quimioterapia. 4. Al menos 1 lesión de la enfermedad mensurable >1,5 cm en al menos una dimensión por tomografía computarizada (TAC), tomografía por emisión de positrones (PET)/CT-PET o resonancia magnética nuclear (RM) 5. Estado funcional del Grupo oncológico cooperativo de la Costa Este (ECOG) ?2 (corresponde a un estado funcional de Karnofsky [(KPS) ?60 %]) Para todos los criterios de inclusion refierase al protocolo |
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E.4 | Principal exclusion criteria |
1. Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B FL 2. Refractory to BR, defined as: - Progression of disease while receiving or within 6 months of completing bendamustine + rituximab therapy 3. Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any of the study drugs 4. Received prior allogeneic transplant 5. Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor 6. Infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). 7. History of tuberculosis treatment within the two years prior to randomization 8. History of chronic liver disease, veno-occlusive disease, or alcohol abuse 9. Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids > 20 mg of prednisone (or equivalent) daily (QD) 10. Ongoing treatment for systemic bacterial, fungal, or viral infection at screening 11. Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening 12. Concurrent active malignancy other than adequately treated non-melanoma skin cancer or lentigo maligna without evidence of invasive disease or adequately treated carcinoma in situ without evidence of disease 13. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or a pacemaker within the last 6 months prior to screening For full exclusion criteria list, refer to protocol. |
1. Indicios clínicos de transformación a un subtipo más agresivo de linfoma o FL de grado 3B 2. Resistencia a BR, definida como: - PE mientras recibe tratamiento con bendamustina + rituximab o dentro de los 6 meses posteriores a la finalización del tratamiento 3. Reacción alérgica o anafiláctica grave a cualquier terapia con anticuerposmonoclonales, proteína murina o hipersensibilidad conocida a cualquier medicamento del estudio 4. Haber recibido un alotrasplante previo 5. Haber recibido tratamiento previo con un inhibidor de la fosfoinositida-3-cinasa (PI3K) 6. Infección por hepatitis B, hepatitis C o virus de la inmunodeficiencia humana (VIH) 7. Antecedentes de tratamiento contra la tuberculosis dentro de los dos años previos a la aleatorización 8. Antecedentes de hepatopatía crónica, enfermedad veno-oclusiva o alcoholismo 9. Tratamiento en curso con inmunosupresores crónicos (p. ej., ciclosporina) o esteroides sistémicos >20 mg de prednisona (o equivalente) por día 10. Tratamiento en curso para infección bacteriana, fúngica o vírica en la selección 11. Imposibilidad para recibir tratamiento profiláctico del Pneumocystis, virus de herpes simple (HSV) o herpes zóster (VZV) en la selección 12. Neoplasia maligna activa simultánea que no sea carcinoma cutáneo no melanocítico adecuadamente tratado o lentigo maligno sin indicios de enfermedad invasiva ,o carcinoma localizado del cuello del útero adecuadamente tratado sin indicios de enfermeda 13. Antecedentes de accidente cerebrovascular, angina inestable, infarto de miocardio o arritmia ventricular que requirieron medicación o un marcapasos en el plazo de los últimos 6 meses anteriores a la selección |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-Free Survival (PFS), defined as the time from randomization to documented progressive disease (PD) according to the revised International Working Group (IWG) criteria as assessed by the Independent Review Committee (IRC), or death due to any cause |
Supervivencia sin progresión (SSP), definida como el tiempo desde la aleatorización hasta la progresión documentada de la enfermedad (PE), conforme a los criterios del Grupo Internacional de Trabajo (IWG) según la evaluación del Comité de revisión independiente (CRI) o la muerte por cualquier causa. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From date of enrollment until the date of first documentation of progression or date of death from any cause, whatever came first, assessed up to 78 months |
Desde la primera inclusión hasta la documentacion de la primera progresion o muerte (lo que sea primero) evaluado hasta 78 meses. |
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E.5.2 | Secondary end point(s) |
-Complete Response (CRR): Time Frame is every 3-6 Cycles (each cycle is 28 days) from date of randomization, until date of first documented progression. Subjects will be evaluated for progression through the primary analysis of the study or 5 years from randomization, whichever is later. -Overall Response Rate (ORR) : Time Frame is every 3-6 Cycles (each cycle is 28 days) from date of randomization, until date of first documented progression. Subjects will be evaluated for progression through the primary analysis of the study or 5 years from randomization, whichever is later. -Overall Survival (OS): Time Frame is every 6 months for up to 5 years from date of randomization. -Duration of Response (DOR): Time Frame is every 3-6 Cycles (each cycle is 28 days) from date of randomization, until date of first documented progression. Subjects will be evaluated for progression through the primary analysis of the study or 5 years from randomization, whichever is later. -Safety (Treatment- emergent adverse events (TEAEs) and changes in safety laboratory values) :Time Frame is Continuous from informed consent until 30 days from last dose -Pharmacokinetics (PK): Time Frame is Cycle 1 and Cycle 2 (each cycle is 28 days)] to evaluate the Duvelisib concentration in plasma sample. -Pharmacokinetics (PK): Time Frame is Cycle 1 and Cycle 2 (each cycle is 28 days)] to evaluate IPI-656 (metabolite) concentration in plasma sample. |
Tasa de Respuesta completa (TRC): El marco de tiempo es de cada 3-6 ciclos (cada ciclo es de 28 días) desde la fecha de la aleatorización hasta la fecha de la primera progresión documentada. Los sujetos serán evaluados para la progresión a través del análisis primario del estudio o 5 años a partir de la aleatorizacion, el que sea más tarde. -Tasa de respuesta global (TRG): El marco de tiempo es cada 3-6 ciclos (cada ciclo es de 28 días) desde la fecha de la aleatorización hasta la fecha de la primera progresión documentada. Los sujetos serán evaluados para la progresión a través del análisis primario del estudio o 5 años a partir de la asignación al azar, el que sea más tarde. -Supervivencia global (OS): El marco de tiempo es cada 6 meses hasta un máximo de 5 años desde la fecha de la aleatorizacion. -Duración De la Respuesta (DDR): El marco de tiempo es cada 3-6 ciclos (cada ciclo es de 28 días) desde la fecha de la aleatorización hasta la fecha de la primera progresión documentada. Los sujetos serán evaluados para la progresión a través del análisis primario del estudio o 5 años a partir de la aleatorizacion, el que sea más tarde. -Seguridad (Tratamiento- emergentes eventos adversos (TEAEs) y cambios en los valores de seguridad de laboratorio): El marco de tiempo es continuo desde el consentimiento informado hasta 30 días después de la última dosis Farmacocinetica (FC): El marco de tiempo es los ciclos 1 y 2 (cada ciclo es de 28 días)] para evaluar la concentración de Duvelisib en la muestra de plasma. Farmacocinetica (FC): El marco de tiempo es los ciclos 1 y 2 (cada ciclo es de 28 días)] para evaluar la concentración de IPI-656 (metabolito) en la muestra de plasma. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All timeframe are described in section E.5.2 -Complete Response (CRR) -Overall Response Rate (ORR) -Overall Survival (OS) -Duration of Response (DOR) -Safety (Treatment- emergent adverse events (TEAEs) and changes in safety laboratory values) -Pharmacokinetics (PK) |
Todo plazo se describen en la sección E.5.2 -Tasa de Respuesta completa (TRC) -Tasa de respuesta global (TRG) -Supervivencia global (OS) -Duración De la Respuesta (DDR) -Seguridad (Tratamiento- emergentes eventos adversos (TEAEs) y cambios en los valores de seguridad de laboratorio) Farmacocinetica (FC) |
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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 | 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 | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 80 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 |
Austria |
Belarus |
Belgium |
Brazil |
Bulgaria |
Canada |
China |
Colombia |
Czech Republic |
Denmark |
Ecuador |
Egypt |
Estonia |
Finland |
France |
Georgia |
Germany |
Greece |
Guatemala |
Hong Kong |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lebanon |
Lithuania |
Malaysia |
Mexico |
New Zealand |
Panama |
Peru |
Philippines |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Singapore |
Slovenia |
South Africa |
Spain |
Taiwan |
Thailand |
Turkey |
Ukraine |
United Kingdom |
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 |
Ultima visita del ultimo paciente |
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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 | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |