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
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Linfoma /leucemia di Burkitt o di tipo Burkitt, linfoma diffuso a grandi cellule B oppure altri linfomi a cellule B mature aggressivi (CD20+) recidivati/refrattari |
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E.1.1.1 | Medical condition in easily understood language |
Lymphoma of B-cell origin
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Linfoma che ha origine dalle cellule 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 | 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.1.2 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.1.3 | 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. |
Gli obiettivi primari dello studio sono quelli di valutare il profilo di sicurezza e di farmacocinetica di epcoritamab in monoterapia in pazienti pediatrici (e in giovani adulti) affetti da linfoma/leucemia di Burkitt o di tipo Burkitt, DLBCL o altri linfomi aggressivi a cellule B mature (CD20+) recidivati/refrattari, che non sono riusciti ad ottenere la remissione con la terapia di re-induzione o non sono in grado di ricevere ulteriore trattamento di consolidamento con terapia cellulare. |
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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. |
L’obiettivo secondario dello studio è quello di valutare l’efficacia preliminare e l’immunogenicità di epcoritamab in monoterapia. |
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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. |
1. Soggetti di età >= 1 anno e < 18 anni al momento della diagnosi primaria di linfoma/leucemia di Burkitt o di tipo Burkitt, DLBCL, oppure altri linfomi aggressivi a cellule B mature (CD20+). Sono inoltre eleggibili pazienti di età fino a 25 anni affetti da linfoma/leucemia di Burkitt o di tipo Burkitt.
2. Malattia con conferma istologica (tessuto tumorale) in base ad esami eseguiti localmente.
3. Pazienti con malattia recidivata o malattia refrattaria primaria (secondo quanto indicato sopra) che soddisfino qualsiasi fra i seguenti criteri: • Malattia progressiva in qualsiasi momento nel corso della di chemioimmunoterapia di seconda linea • Miglior risposta di malattia stabile (SD) dopo un minimo di 2 cicli di chemioimmunoterapia di seconda linea • Miglior risposta di risposta parziale (PR) dopo un minimo di 3 cicli di chemioimmunoterapia di seconda linea • Risposta Completa dopo un minimo di 3 cicli di chemioimmunoterapia di seconda linea, ma condizioni generali non adeguate (unfit) oppure non idoneo al trattamento di consolidamento con terapia cellulare • Non in Risposta completa e non in grado di iniziare o di tollerare (in altre parole, deve interrompere) chemioimmunoterapia di seconda linea • Aver ricevuto terapia cellulare (trapianto allogenico o autologo oppure terapia CAR-T) come trattamento di consolidamento senza ottenere o mantenere una risposta completa
4. Risoluzione degli effetti tossici di chemioimmunoterapia pregressa
5. Punteggio relativo allo stato funzionale >= 50 secondo Lansky (< 16 anni al momento della valutazione) oppure Karnofsky (>= 16 anni al momento della valutazione) oppure punteggio ECOG <= 2.
6. Funzione midollare, epatica e renale adeguate.
7. Per i pazienti che non abbiano raggiunto la maggiore età, presenza di genitore o tutore legale disposto e in grado di fornire il consenso informato scritto, e soggetto disponibile e in grado di fornire l’assenso, secondo quanto appropriato per l’età e la nazione. |
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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. Noto interessamento da linfoma del sistema nervoso centrale allo screening confermato da scansioni cerebrali con RM/TAC/PET allo screening (saranno eleggibili pazienti con evidenza di malattia dell’SNC esclusivamente nel liquido cerebrospinale).
2. Attualmente in trattamento con terapia antineoplastica, comprese chemioterapia (ad eccezione della terapia intratecale), radioterapia, farmaci a piccola molecola, anticorpi monoclonali, terapia cellulare oppure altri agenti sperimentali.
3. Altre neoplasie maligne che necessitano di terapia. |
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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.
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Gli endpoint primari sono la sicurezza e la tollerabilità, compresi gli eventi avversi di interesse speciale (adverse events of special interest, AESI) rappresentati da sindrome di rilascio di citochine (Cytokine Release Syndrome, CRS), sindrome da neurotossicità associata alle cellule immunitarie (Immune Cell-Associated Neurotoxicity Syndrome, ICANS) e sindrome da lisi tumorale clinica (Clinical Tumor Lysis Syndrome, CTLS), e parametri di PK per epcoritamab in 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 sicurezza e tollerabilità verranno valutate nel corso dell’intero studio clinico
I parametri di farmacocinetica vengono valutati alle seguenti tempistiche: • Ciclo 1: Giorno 10, dal Giorno 15 al Giorno 17 , Giorno 19, Giorno 22 • Ciclo 2: Giorno 1, dal Giorno 8 al Giorno 10, Giorno 12, Giorno 15 • Dal Ciclo 3 al Ciclo 10: Giorno 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]) |
•Tasso di risposta completa (CR) in base ai criteri International Pediatric Non-Hodgkin Lymphoma Response Criteria •Sopravvivenza libera da eventi (event-free survival, EFS) •Sopravvivenza globale (overall survival, OS) •Tasso di esecuzione di trapianto di cellule staminali oppure di avvio di terapia CAR-T (chimeric antigen receptor T-cell) •Risposta globale (overall response, OR) •Durata della risposta (duration of response, DOR) •Durata della risposta completa (duration of complete response, DOCR) •Immunogenicità (anticorpi anti-farmaco [ADA] e anticorpi neutralizzanti l’effetto del farmaco [nAb]) |
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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. |
Saranno eseguite valutazioni della malattia (TAC/RM/PET) per tutti pazienti prima della somministrazione di epcoritamab il Giorno 1 e alle seguenti tempistiche rispetto al Giorno 1: Settimana 6, Settimana 12, Settimana 24, Settimana 36, Settimana 48, 18 mesi e 24 mesi, oltre che prima di avviare la terapia successiva, e secondo quanto clinicamente indicato. Per i pazienti che non ottengono una CR nel corso della terapia con epcoritamab sono previste valutazioni aggiuntive della malattia alle tempistiche Settimana 18, Settimana 30, Settimana 42 e in seguito ogni 3 mesi. I pazienti saranno seguiti per un minimo di 3 anni dopo l’arruolamento. |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
a braccio singolo |
single-arm |
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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 | 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 | 2 |
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 | Information not present in EudraCT |
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 |
Czechia |
France |
Germany |
Israel |
Italy |
Korea, Republic of |
Netherlands |
Russian Federation |
Spain |
Turkey |
United Kingdom |
United States |
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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. |
Per fine dello studio si intende la data dell’ultima visita dell’ultimo soggetto oppure la data dell’ultimo contatto di follow-up, quale di questi eventi avvenga per ultimo. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 |