E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/refractory Burkitt's or Burkitt-like lymphoma/leukemia, Diffuse large B-cell lymphoma , or other aggressive mature (CD20+) B-cell lymphomas |
Linfoma / leucemia de Burkitt o similar a Burkitt o recidivante / refractario, linfoma difuso de células B grandes u otros linfomas agresivos de células B maduras (CD20 +) |
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E.1.1.1 | Medical condition in easily understood language |
Lymphoma of B-cell origin |
Lymphoma de origen de células 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 | HLT |
E.1.2 | Classification code | 10006596 |
E.1.2 | Term | Burkitt's lymphomas |
E.1.2 | System Organ Class | 100000004851 |
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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 | 10003903 |
E.1.2 | Term | B-cell lymphoma refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10012822 |
E.1.2 | Term | Diffuse large B-cell lymphoma refractory |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of the study are to evaluate the safety and Pharmacokinetic profile of epcoritamab monotherapy in pediatric patients (and young adults) with relapsed/refractory Burkitt's or Burkitt-like lymphoma/leukemia, DLBCL, or other aggressive mature (CD20+) B-cell lymphomas who have failed to reach remission with re-induction therapy or who are unable to receive further consolidation with cell therapy. |
Los objetivos principales del estudio consisten en evaluar el perfil de seguridad y farmacocinética del epcoritamab en monoterapia en pacientes pediátricos (y adultos jóvenes) con linfoma/leucemia de Burkitt o de tipo Burkitt recidivante o resistente, LDCBG u otros linfomas de linfocitos B (CD20+) maduros agresivos que no han logrado la remisión con el tratamiento de reinducción o que no pueden recibir consolidación ulterior con terapia celular. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to evaluate the preliminary efficacy and immunogenicity of epcoritamab monotherapy. |
El objetivo secundario del estudio es evaluar la eficacia preliminar y la inmunogenicidad de la monoterapia con epcoritamab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects ≥ 1 and < 18 years old at time of primary diagnosis with Burkitt's or Burkitt-like lymphoma/leukemia, DLBCL, or other aggressive mature (CD20+) B-cell lymphomas. Patients up to 25 years of age with Burkitt's or Burkitt-like lymphoma/leukemia are also eligible.
2. Disease pathologically confirmed (tumor tissue) by local testing.
3. Patients with relapsed or primary refractory disease (as above) meeting any of the following criteria: •Progressive disease at any time during second-line chemoimmunotherapy •Best response of stable disease (SD) after a minimum of 2 cycles of second-line chemoimmunotherapy •Best response of partial response (PR) after a minimum of 3 cycles of second-line chemoimmunotherapy •Complete Response after a minimum of 3 cycles of second-line chemoimmunotherapy therapy but unfit or ineligible for consolidation with cell therapy •Not in Complete response and unable to initiate or tolerate (i.e., must discontinue) second-line chemoimmunotherapy •Have received cell therapy (allogeneic or autologous transplant or CAR-T therapy) as consolidation but have not obtained or maintained a complete response
4. Recovery from toxic effects of prior chemoimmunotherapy
5. Performance status by Lansky (< 16 years old at evaluation) or Karnofsky (≥ 16 years old at evaluation) score ≥ 50 or ECOG score ≤ 2
6. Adequate bone marrow, hepatic, and renal function.
7. For those patients who have not reached the age of consent, parent or legal guardian with the willingness and ability to provide written informed consent and subject willing and able to give assent, as appropriate for age and country. |
Sujetos de edad ≥1 y <18 años en el momento del diagnóstico primario con linfoma/leucemia de Burkitt o de tipo Burkitt, LDCBG u otros linfomas de linfocitos B (CD20+) maduros agresivos. También podrán participar pacientes de hasta 25 años con linfoma/leucemia de Burkitt o de tipo Burkitt.
2. Enfermedad confirmada anatomopatológicamente (tejido tumoral) mediante análisis locales.
3. Pacientes con enfermedad recidivante o resistente primaria (como se ha indicado anteriormente) que cumplan cualquiera de los criterios siguientes: • Progresión de la enfermedad en cualquier momento durante la QIT de segunda línea. • Mejor respuesta de enfermedad estable (EE) después de un mínimo de 2 ciclos de QIT de segunda línea. • Mejor respuesta de respuesta parcial (RP) después de un mínimo de 3 ciclos de QIT de segunda línea. • RC después de un mínimo de 3 ciclos de QIT de segunda línea, pero el paciente no es apto para recibir consolidación con terapia celular. • Ausencia de RC e incapacidad de iniciar o tolerar (es decir, debe suspenderse) la QIT de segunda línea. • Recepción previa de terapia celular (alo o autotrasplante o terapia CAR-T) como consolidación, pero sin haber obtenido o mantenido una RC.
4. Recuperación de los efectos tóxicos de la quimioinmunoterapia previa.
5. Estado funcional según la puntuación de Lansky (edad <16 años en el momento de la evaluación) o Karnofsky (edad ≥16 años en el momento de evaluación) ≥50 o según la puntuación del ECOG ≤2.
6. Función medular, hepática y renal adecuada
7. En los pacientes que no hayan alcanzado la edad de consentimiento, progenitor o tutor legal con voluntad y capacidad de otorgar su consentimiento informado por escrito y paciente con voluntad y capacidad de otorgar su asentimiento, según proceda, para la edad y el país. |
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E.4 | Principal exclusion criteria |
1. Known CNS involvement by lymphoma at screening as confirmed by screening MRI/CT/PET brain scans (patients with evidence of CNS disease only in the CSF will be eligible).
2. Currently receiving anti-cancer therapy, including chemotherapy (excluding intrathecal therapy), radiotherapy, small molecules, monoclonal antibodies, cell therapy, or other investigational agents.
3. Other malignancy requiring therapy. |
1.afectación conocida del SNC por el linfoma en el periodo de selección, confirmado mediante la RM/TC/PET cerebral de selección (solo podrán participar pacientes con signos de afectación del SNC en el LCR).
2.estar recibiendo actualmente tratamiento antineoplásico, como quimioterapia (excepto tratamiento intratecal), radioterapia, moléculas pequeñas, anticuerpos monoclonales, terapia celular u otros fármacos experimentales.
3. Otra neoplasia maligna que requiera tratamiento. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are safety and tolerability, including adverse events of special interest (AESIs) of Cytokine Release Syndrome (CRS), Immune Cell-Associated Neurotoxicity Syndrome (ICANS), and Clinical Tumor Lysis Syndrome (CTLS), and PK parameters of epcoritamab monotherapy. |
Los criterios de valoración principales son la seguridad y la tolerabilidad, incluidos los acontecimientos adversos de interés especial (AAIE) de síndrome de liberación de citocinas (SLC), síndrome de neurotoxicidad asociada a células inmunitarias (SNACI) y síndrome de lisis tumoral clínico (SLTC), así como los parámetros farmacocinéticos de epcoritamab en monoterapia. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety and tolerability are evaluated throughout the study.
Pharmacokinetic parameters are evaluated the following timepoint: • Cycle 1: Day 10, Day 15-17, Day 19, Day 22 •Cycle 2: Day 1, Day 8-10, Day 12, Day 15 •Cycle 3-10: Day 1 |
La seguridad y la tolerabilidad se evalúan a lo largo del estudio.
Los parámetros farmacocinéticos se evalúan en el siguiente período de tiempo: •Ciclo 1: Día 10, Día 15-17, Día 19, Día 22 •Ciclo 2: Día, Día 8-10, Día 12, Día 15 •Ciclo 3-10: Día 1 |
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E.5.2 | Secondary end point(s) |
•Complete response rate (CR) per the International Pediatric Non- Hodgkin Lymphoma Response Criteria •Event free survival (EFS) •Overall survival (OS) •Rate of initiation of stem cell transplantation or chimeric antigen receptor T-cell (CAR-T) therapy •Overall Response (OR) •Duration of response (DOR) •Duration of complete response (DOCR) •Immunogenicity (antidrug antibody [ADA] and neutralizing anti-drug antibodies [nAb]) |
• CR per the International Pediatric Non-Hodgkin Lymphoma Response Criteria • Supervivencia sin episodios (SSE). • Supervivencia global (SG). • Tasa de inicio de trasplante de células madre o de terapia CAR-T (linfocitos T con receptores antigénicos quiméricos). • Respuesta global (RG). • Duración de la respuesta (DR). • Duración de la RC (DRC). • Inmunogenicidad (anticuerpos contra el fármaco [ACF] y anticuerpos contra el fármaco neutralizantes [AcN]). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Disease evaluation (CT/MRI/PET) will be performed for all patients prior to administration of epcoritamab on Day 1 and at the following time points relative to Day 1: W6, W12, W24, W36, W48, 18 months, and 24 months, as well as prior to initiation of subsequent therapy, and as clinically indicated. Patients who do not attain a CR during therapy with epcoritamab will have additional disease assessments at W18, W30, W42, and every 3 months thereafter. Patients will be followed for a minimum of 3 years after enrollment. |
Se realizará una evaluación de la enfermedad (TC/RM/PET) en todos los pacientes antes de la administración de epcoritamab el día 1 y en los momentos siguientes con respecto al día 1: S6, S12, S24, S36, S48, 18 y 24 meses, así como antes del inicio del tratamiento posterior y cuando esté clínicamente indicado. Los pacientes que no logren una RC durante el tratamiento con epcoritamab se someterán a evaluaciones adicionales de la enfermedad en las semanas 18, 30 y 42 y, posteriormente, cada tres meses. Los pacientes serán objeto de seguimiento durante un mínimo de 3 años después de su inclusión |
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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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
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 |
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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.8.3 |
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 | 18 |
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 |
Turkey |
Canada |
Czechia |
Germany |
Israel |
Italy |
Korea, Republic of |
Netherlands |
Russian Federation |
Spain |
United Kingdom |
United States |
France |
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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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The end-of-study is defined as the date of the last subject's last visit or date of the last follow-up contact, whichever is later. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |