E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas |
Linfomas Recidivantes/Resistentes positivos para el Virus de Epstein-Barr (VEB+) |
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E.1.1.1 | Medical condition in easily understood language |
Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas |
Linfomas Recidivantes/Resistentes positivos para el Virus de Epstein-Barr (VEB+) |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071441 |
E.1.2 | Term | Epstein-Barr virus associated 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 evaluate the anti-tumor activity of the combination treatment of nanatinostat (Nstat) with valganciclovir (VGCV) based on objective tumor response rates |
Evaluar la actividad antitumoral del tratamiento combinado de nanatinostat (Nstat) con valganciclovir (VGCV) basado en las tasas de respuesta tumoral objetiva. |
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E.2.2 | Secondary objectives of the trial |
To determine the duration of tumor control To determine survival outcomes To describe the safety profile of the combination treatment of Nstat with VGCV To generate pharmacokinetic (PK) data |
+ Determinar la duración del control tumoral. + Determinar los resultados de supervivencia. + Describir el perfil de seguridad del tratamiento combinado de Nstat con VGCV. + Generar datos de farmacocinética (FC) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult patients age ≥18 years at the time of informed consent. 2. EBV+ relapsed/refractory lymphoma following 2 or more prior systemic therapies 3. EBV+ DLBCL, NOS: Must have received at least one course of an anti-CD20 immunotherapy, and at least one course of anthracycline-based chemotherapy 4. PTLD: Must have received immunotherapy with an anti-CD20 agent. 5. Hodgkin lymphoma: Must have received at least one course of antracycline-based chemotherapy. Patients with classical Hodgkin lymphoma should have failed or be ineligible for an anti-PD-1 agent and CD30-directed therapy. 6. For extranodal NK/T-cell lymphoma patients only: Relapsed/refractory disease following 1 or more prior systemic therapies. Patients must have failed an a sparaginase-containing regimen. 7. No available therapies in the opinion of the investigator. 8. Not eligible for high-dose chemotherapy with allogeneic/autologous stem cell transplantation or CAR-T Therapy. 9. Measurable disease per Lugano 2007. 10. ECOG performance status 0, 1, 2. 11. Adequate bone marrow function. |
1.Pacientes adultos de ≥18 años en el momento del consentimiento informado. 2. Linfoma recidivante/resistente VEB+ después de 2 o más tratamientos sistémicos previos con confirmación histológica 3. En el caso del LDLBG sin especificar VEB+: deben haber recibido al menos un ciclo de inmunoterapia anti-CD20, y al menos un ciclo de quimioterapia basada en antraciclinas. 4. TLPT: los pacientes deben haber recibido inmunoterapia con un fármaco anti-CD20. 5. Linfoma de Hodgkin: deben haber recibido al menos un ciclo de quimioterapia basada en antraciclinas. Los pacientes con linfoma de Hodgkin clásico deben haber fracasado o no ser aptos para recibir un fármaco anti-PD-1 ni tratamiento dirigido a CD30. 6. Solo para pacientes con linfoma extraganglionar de linfocitos NK/T: enfermedad recidivante/resistente tras 1 o más tratamientos sistémicos previos. Los pacientes debían haber fracasado con una pauta posológica que contuviera asparaginasa. 7. No hay tratamientos estándar disponibles en opinión del investigador. 8. No ser apto para quimioterapia en dosis altas con trasplante alogénico/autólogo de células madre o tratamiento CAR-T en el momento de la entrada en el estudio. 9. Enfermedad medible por Lugano 2007. 10. Estado funcional del Grupo Oncológico Cooperativo de la Costa Este (ECOG) de 0, 1 o 2 11. Función de la médula ósea adecuada |
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E.4 | Principal exclusion criteria |
1. Presence or history of central nervous system (CNS) involvement by lymphoma. 2. Systemic anticancer therapy or CAR within 21 days. 3. Antibody (anticancer) agents within 28 days. 4. Less than 60 days from prior autologous hematopoietic stem cell or solid organ transplant. 5. Less than 90 days from prior allogeneic transplant. 6. Daily corticosteroids (≥20 mg of prednisone or equivalent) within week prior to Cycle 1 Day 1. 7. Inability to take oral medication, malabsorption syndrome or any other gastrointestinal condition (nausea, diarrhea, vomiting) that may impact the absorption of nanatinostat and valganciclovir. 8. Active infection requiring systemic therapy (Excluding viral upper respiratory tract infections |
1. Presencia o antecedentes de afectación del sistema nervioso central (SNC) a causa del linfoma. 2. Tratamiento antineoplásico sistémico o CAR-T en los 21 días previos. 3. Anticuerpos (antineoplásicos) en los 28 días previos. 4. Han transcurrido menos de 60 días después de un trasplante autólogo de células madre hematopoyéticas o de órgano sólido. 5. Han transcurrido menos de 90 días desde el trasplante alogénico previo. 6. Recibir corticoesteroides (20 mg/día de prednisona o equivalente) durante la última semana antes del día 1 del ciclo 1. 7. Incapacidad para tomar medicación por vía oral, síndrome de malabsorción o cualquier otra afección gastrointestinal (náuseas, diarrea, vómitos) que pueda afectar a la absorción de nanatinostat y valganciclovir. 8. Infección activa que requiera tratamiento sistémico (se excluyen las infecciones víricas de las vías respiratorias altas). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) as assessed by an Independent Review Committee (IRC) per the 2007 International Working Group (IWG) criteria. |
Tasa de respuesta objetiva (TRO) evaluada por un Comité de Revisión Independiente (CRI), según los criterios del Grupo de Trabajo Internacional de 2007 (International Working Group, IWG) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy endpoint is ORR assessed by an IRC every 8 weeks until 24 weeks, and then every 12 weeks for the remainder of the study. |
La variable principal de eficacia es la TRO evaluada por un CRI cada 8 semanas hasta la semana 24, y después cada 12 semanas durante el resto del estudio |
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E.5.2 | Secondary end point(s) |
• Duration of response (DOR) • Time to next anti-lymphoma treatment • Progression-free survival • Time to progression • Overall survival (OS) • Pharmacokinetic (PK) parameters (eg, time to maximum plasma concentration [tmax], maximum plasma concentration [Cmax], area under the plasma concentration-time curve [AUC]). |
+ Duración de la respuesta (DR) + Tiempo transcurrido hasta el siguiente tratamiento contra el linfoma + Supervivencia sin progresión. + Tiempo hasta la progresión. + Supervivencia global (SG). + Parámetros farmacocinéticos (p. ej., tiempo hasta la concentración plasmática máxima [tmáx.], concentración plasmática máxima [Cmáx.], área bajo la curva de concentración plasmática frente al tiempo [ABC]). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall survival,Time to next anti-lymphoma treatment, Duration of response, Progression free survival |
Supervivencia global, Tiempo transcurrido hasta el siguiente tratamiento contra el linfoma, Duración de la respuesta, Supervivencia sin progresión |
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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) | 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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Estudio con diseño en cesta |
basket design study |
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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 | 8 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Singapore |
Taiwan |
United States |
France |
Spain |
Germany |
Italy |
United Kingdom |
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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
|
The end of the study occurs when all patients have either progressed, discontinued, died, become lost to follow-up, or have maintained a CR, PR, or SD for at least 3 years, or when the trial is terminated by the Sponsor. |
El final del estudio tiene lugar cuando todos los pacientes hayan sufrido progresión, discontinuado, fallecido, pasen a perderse para el seguimiento, o hayan mantenido una RC, RP o EE durante al menos 3 años, o cuando el promotor decida darlo por terminado |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |