E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse Large B-Cell Lymphoma |
Linfoma difuso de células B grandes |
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E.1.1.1 | Medical condition in easily understood language |
Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of cell that is responsible for producing antibodies. |
El linfoma difuso de células B grandes (DLBCL) es un cáncer de células B, un tipo de célula responsable de producir anticuerpos. |
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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 | 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 evaluate the efficacy of glofitamab in combination with R-CHOP in circulating-tumor DNA (ctDNA) high-risk patients with previously untreated DLBCL based on end of treatment (EOT) complete response (CR) rate as determined by the investigator according to 2014 Lugano Response Criteria |
Evaluar la eficacia de glofitamab en combinación con R-CHOP en pacientes de alto riesgo con LDCBG no tratado previamente y ADNtc, basado en la tasa de respuesta completa (RC) al final del tratamiento (EOT) según lo determinado por el investigador de acuerdo con Criterios de respuesta de Lugano 2014. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of glofitamab in combination with R-CHOP in ctDNA high-risk patients with previously untreated DLBCL based on objective response rate (ORR) at the EOT, progression-free survival (PFS) and overall survival (OS) as determined by the investigator according to 2014 Lugano Response Criteria • To evaluate the safety of glofitamab in combination with R-CHOP in ctDNA high-risk participants with DLBCL • To characterize the serum pharmacokinetics (PK) profile of glofitamab in combination with R-CHOP • To evaluate potential effects of anti-drug antibodies (ADAs) |
- Evaluar la eficacia de glofitamab en combinación con R-CHOP en pacientes de alto riesgo con LDCBG no tratado previamente y ADNtc, basado en TRO al final del tratamiento (EOT) según lo determinado por el investigador conforme a los criterios de respuesta de Lugano de 2014. - Evaluar la eficacia de glofitamab en combinación con R-CHOP en pacientes de alto riesgo con LDCBG y ADNtc. - Caracterizar el perfil farmacocinético en suero de glofitamab en combinación con R-CHOP. - Evaluar los efectos potenciales de los ADAs (anti-drug antibodies) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age >=18 years at the time of signing Informed Consent Form • Previously untreated patients with CD20-positive DLBCL, including one of the following diagnoses made according to the 2016 World Health Organization (WHO) classification of lymphoid neoplasms o DLBCL, not otherwise specified, including GCB and ABC/non-GCB types as well as double-expressor lymphoma (coexpression of MYC and BCL2) o High-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 translocations o Patients with de novo transformed follicular lymphoma (patients with discordant bone marrow involvement, i.e., evidence of low-grade histology in bone marrow) may be considered after discussion with the Medical Monitor • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0–2 • International Prognostic Index (IPI): 1-5 • Life expectancy of >=6 months • Adequate biomarker blood samples prior to initiation of R-CHOP on Day 1 of Cycle 1 and on Day 1 of Cycle 2 submitted for screening for determination of ctDNA status • At least one bi-dimensionally fluorodeoxyglucose (FDG)-avid measurable lymphoma lesion on positron emission tomography/computed tomography (PET/CT) scan • Left ventricular ejection fraction (LVEF) >=50%, as determined on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO) • Adequate hematopoietic function • Contraception use Additional Inclusion Criterion for ctDNA High-Risk Participants • Plasma sample evaluated to be ctDNA high risk, defined as <2-log fold reduction in ctDNA levels between Day 1 of Cycle 1 and Day 1 of Cycle 2 by central laboratory assessment |
• Edad >=18 años en el momento de firmar el documento de consentimiento informado. • Pacientes con LDLBG CD20-positivo no tratados previamente, incluido uno de los siguientes diagnósticos según la clasificación de las neoplasias linfoides de la OMS de 2016. – LDLBG, sin especificar, incluidos los tipos GCB y ABC/no GCB, así como el linfoma con doble expresión (coexpresión de MYC y BCL2) Linfoma de linfocitos B de alto grado (LLBAG) con translocaciones de MYC y BCL2 o BCL6 Podrá considerarse la participación de pacientes con linfoma folicular transformado de novo (pacientes con afectación discordante de la médula ósea, es decir, signos de histología de bajo grado en la médula ósea) previa consulta con el monitor médico. • Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0–2 • Índice Pronóstico Internacional (IPI) 1-5 • Esperanza de vida >= 6 meses. • Muestras de sangre adecuadas para análisis de biomarcadores antes del inicio de R-CHOP el día 1 del ciclo 1 y el día 1 del ciclo 2 enviadas para la selección a fin de determinar el estado del ADNtc. • Al menos una lesión linfomatosa mensurable en dos dimensiones con avidez por FDG en la PET/TC • Fracción de eyección del ventrículo izquierdo >= 50%, determinada mediante ventriculografía isotópica en equilibrio (MUGA) o ecocardiografía transtorácica. • Función hematopoyética adecuada • Uso de anticoncepción Criterio de inclusión adicional para pacientes de alto riesgo con ADNtc • Muestra de plasma considerada de alto riesgo con ADNtc, definida como una reducción logarítmica < 2 veces de la concentración de ADNtc entre el día 1 del ciclo 1 y el día 1 del ciclo 2 según la evaluación del laboratorio central. |
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E.4 | Principal exclusion criteria |
• Current diagnosis of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma (gray-zone lymphoma), primary mediastinal (thymic) large B-cell lymphoma, Burkitt lymphoma, central nervous system (CNS) lymphoma (primary or secondary involvement), primary effusion DLBCL, and primary cutaneous DLBCL • Contraindication to any of the individual components of R-CHOP, including prior receipt of anthracyclines, history of severe allergic or anaphylactic reactions to murine monoclonal antibodies, or known sensitivity or allergy to murine products • Prior treatment for indolent lymphoma • Prior solid organ or allogeneic stem cell transplant • Prior therapy for DLBCL and high-grade B-cell lymphoma (HGBCL) with the exception of palliative, short-term treatment with corticosteroids • Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the final dose of R-CHOP, 3 months after the final dose of tocilizumab (if applicable), or 2 months after the final dose of glofitamab |
• Diagnóstico actual de linfoma de linfocitos B, inclasificable, con características intermedias entre LDLBG y linfoma de Hodgkin clásico (linfoma de la zona gris), linfoma mediastínico primario de linfocitos B grandes (tímico), linfoma de Burkitt, linfoma del SNC (afectación primaria o secundaria), LDLBG con derrame primario y LDLBG cutáneo primario. • Contraindicación de cualquiera de los componentes individuales de R CHOP, como tratamiento previo con antraciclinas, antecedentes de reacciones alérgicas o anafilácticas graves a anticuerpos monoclonales murinos o sensibilidad o alergia conocidas a productos de origen murino. • Tratamiento previo del linfoma poco activo • Trasplante de órgano sólido o alotrasplante de células progenitoras previo (Trasplante previo de órganos sólidos o células madre alogénicas) • Tratamiento previo del LDLBG y el LLBAG con la excepción del tratamiento paliativo a corto plazo con corticosteroides. • Embarazo o lactancia, o intención de quedarse embarazada durante el estudio o en los 12 meses siguientes a la última dosis de R-CHOP, 3 meses después de la última dosis de tocilizumab (si procede) o 2 meses después de la última dosis de glofitamab. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. EOT CR rate, as determined by the investigator according to the 2014 Lugano Response Criteria for Malignant Lymphoma |
1. Tasa de RC al FDT, según lo determinado por el investigador conforme a los criterios de respuesta de Lugano para el linfoma maligno de 2014. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 24 months |
1. Hasta aproximadamente 24 meses |
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E.5.2 | Secondary end point(s) |
1. ORR at the EOT, as determined by the investigator according to the 2014 Lugano Response Criteria 2. PFS, as determined by the investigator according to the 2014 Lugano Response Criteria 3. OS 4. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) 5. Tolerability, as assessed by dose modifications, dose intensity, and study treatment discontinuation because of adverse events 6. Serum concentrations of glofitamab at specified timepoints 7. Serum trough concentrations of glofitamab at specified timepoints 8. Maximum concentration (Cmax) of glofitamab at specified timepoints 9. Area under the concentration–time curve (AUC) of glofitamab at specified timepoints 10. Relationship between ADA status and efficacy, safety, or PK endpoints |
1.TRO al FDT, según lo determinado por el investigador conforme a los criterios de respuesta de Lugano de 2014. 2.SLP, según lo determinado por el investigador conforme a los criterios de respuesta de Lugano de 2014. 3.SG 4.Incidencia e intensidad de los acontecimientos adversos, con determinación de la intensidad conforme a los criterios NCI-CTCAE v5.0. 5.Tolerabilidad, evaluada mediante las modificaciones de la dosis, la intensidad de la dosis y la suspensión del tratamiento del estudio por acontecimientos adversos. 6.Concentración sérica de glofitamab en momentos especificados. 7.Concentración sérica mínima de glofitamab en momentos especificados. 8. Concentración máxima (Cmax) de glofitamab en momentos específicos 9. Área bajo la curva de concentración-tiempo (AUC) de glofitamab en momentos específicos 10.Relación entre la presencia de ADA( ACF) y los criterios de valoración de eficacia, seguridad o farmacocinética |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3. Up to approximately 24 months 4-5. Up to 90 days after the final dose of study treatment 6-10. During treatment (up to approximately 10 months) and at treatment completion/discontinuation visit |
1-3. Hasta aproximadamente 24 meses 4-5. Hasta 90 días después de la dosis final del tratamiento del estudio. 6-10. Durante el tratamiento (hasta aproximadamente 10 meses) y en la visita de finalización / interrupción del tratamiento |
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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 | 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 | 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
| 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 | 4 |
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 |
United States |
Denmark |
France |
Netherlands |
Poland |
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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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 | 1 |
E.8.9.1 | In the Member State concerned days | 13 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 13 |