E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory diffuse large B-cell lymphoma |
Linfoma difuso de células B grandes recidivante o resistente al tratamiento |
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E.1.1.1 | Medical condition in easily understood language |
A type of non-Hodgkin lymphoma (NHL). NHL is a cancer of the lymphatic system. |
Un tipo de linfoma no Hodgkin (LNH). El LNH es un cáncer del sistema linfático. |
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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 | LLT |
E.1.2 | Classification code | 10012820 |
E.1.2 | Term | Diffuse large B-cell lymphoma NOS |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Determine the safety and efficacy of the combination of plamotamab, tafasitamab, and lenalidomide compared to tafasitamab and lenalidomide in adult subjects with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). |
Determinar la seguridad y la eficacia de la combinación del plamotamab, el tafasitamab y la lenalidomida en comparación con el tafasitamab y la lenalidomida en pacientes adultos con linfoma difuso de células B grandes recidivante o resistente al tratamiento (LDCBG R-R). |
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E.2.2 | Secondary objectives of the trial |
Compare the combination of plamotamab, tafasitamab, and lenalidomide to tafasitamab and lenalidomide for the assessments as detailed in the protocol. |
comparar la combinación del plamotamab, el tafasitamab y la lenalidomida con el tafasitamab y la lenalidomida para las evaluaciones detalladas en el protocolo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed diagnosis of DLBCL, NOS, including DLBCL arising from low grade lymphoma • CD20+ and CD19+ lymphoma • Archival paraffin embedded tumor tissue or unstained slides must be available for retrospective cell of origin determination • Relapsed or refractory DLBCL • At least 1 prior systemic line(s) of therapy, one of which must have included multi-agent chemoimmunotherapy that includes an anti-CD20 monoclonal antibody. • At least 1 bidimensionally measurable disease site. The lesion must have a greatest transverse diameter of ≥ 1.5 cm and greatest perpendicular diameter of ≥ 1.0 cm at baseline. The lesion must have a positive finding on positron emission tomography (PET) scan. • Ineligible for or refuse hematopoietic stem cell transplantation (HSCT). • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. • Completed vaccination for the SARS-CoV-2 virus prior to study entry. • Fertile subjects must agree to use 2 highly effective methods of birth control during for at least 6 months (male subjects) and 8 months (female subjects) after the last dose of study treatment. Further inclusion criteria are provided in the protocol. |
• Diagnóstico de LDCBG confirmado histológicamente, sin especificar, incluido el LDCBG surgido a partir de un linfoma de bajo grado. • Linfoma CD20+ y CD19+ • Deberán estar disponibles tejido tumoral de archivo incrustado en parafina o secciones sin teñir para una determinación retrospectiva de la célula de origen • LDCBG recidivante o resistente al tratamiento • Al menos 1 o varias líneas de tratamiento sistémico anterior, una de las cuales debe incluir una quimioinmunoterapia con múltiples fármacos, incluido un anticuerpo monoclonal anti-CD20 • Al menos 1 zona de la lesión medible de forma bidimensional. La lesión debe tener un diámetro transversal máximo ≥1,5 cm y un diámetro perpendicular máximo ≥1,0 cm en el momento basal. La lesión debe detectarse en la tomografía por emisión de positrones (TEP). • Pacientes que no sean aptos para un trasplante de células madre hematopoyéticas (TCMH) o que lo rechacen • Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 a 2 • Vacunación completa contra el virus SARS-CoV-2 antes de entrar en el estudio • Los sujetos fértiles deben aceptar usar 2 métodos anticonceptivos altamente efectivos durante al menos 6 meses (sujetos masculinos) y 8 meses (sujetos femeninos) después de la última dosis del tratamiento del estudio. En el protocolo se proporcionan más criterios de inclusión. |
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E.4 | Principal exclusion criteria |
• Any other histological type of lymphoma, including high-grade B-cell lymphoma, including those with MYC and BCL2 and/or BCL6 rearrangements primary mediastinal (thymic) large B cell (PMBL) or Burkitt lymphoma • A prior diagnosis of CLL (Richter’s Transformation) • Primary central nervous system (CNS) lymphoma Further exclusion criteria are provided in the protocol. |
• Cualquier otro tipo histológico de linfoma, incluido linfoma de linfocitos B de alto grado, incluidos los pacientes con reordenamiento de MYC y BCL2 o BCL6, linfoma de linfocitos B de alto grado sin especificar incluido el linfoma de Burkitt o linfoma mediastínico (tímico) primario de células B grandes (LMPCBG) • Diagnóstico anterior de leucemia linfocítica crónica (LLC) (síndrome de Richter) • Linfoma primario del sistema nervioso central (SNC) En el protocolo se proporcionan más criterios de exclusión. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• For Part 1, safety as measured by incidence of cytokine release syndrome (CRS) and treatment-emergent adverse events (TEAEs) • For Part 2, progression-free survival (PFS) |
•para la parte 1: la seguridad, medida según la incidencia del SLC y de los AAST; y •para la parte 2: la SSP, definida como el tiempo desde la aleatorización hasta la primera incidencia registrada de progresión de la enfermedad o muerte. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• For Part 1 Baseline Day 1 to end of Part 1 • For Part 2 Baseline Day 1 to end of study (EOS) |
• Para la parte 1 desde la evaluacion inicial, Día 1, hasta la finalización de la parte 1. • Para la parte 2 desde la evaluación inicial, Día 1, hasta el final del estudio (FdE) |
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E.5.2 | Secondary end point(s) |
1. Best objective response rate (ORR) 2. Overall survival (OS) 3. Duration of response (DOR) 4. Incidence, timing, and severity of CRS 5. Incidence, timing, and severity of immune effector cell-associated neurotoxicity syndrome (ICANS) 6. Incidence and severity of TEAEs, with severity defined by National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
La mejor tasa de respuesta objetiva (TRO) La SG, definida como el tiempo entre la aleatorización y la muerte Duracion de respuesta (DR) Incidencia, momento y gravedad del SLC Incidencia, momento y gravedad del síndrome de neurotoxicidad asociado a células efectoras inmunitarias Incidencia y gravedad de los AAST en la parte 2, estando la gravedad de acuerdo con los criterios terminológicos comunes para los acontecimientos adversos del National Cancer Institute (NCI) (CTCAE; versión 5.0) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline Day 1 through EOS |
Desde la evaluacion inicial, día 1, hasta el final del estudio |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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) | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 |
Korea, Republic of |
United States |
France |
Spain |
United Kingdom |
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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 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 | 6 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |