E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent or Refractory Classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma |
Linfoma di Hodgkin classico e Linfoma Non-Hodgkin ricorrente o refrattario |
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E.1.1.1 | Medical condition in easily understood language |
Hodgkin Lymphoma and Non-Hodgkin Lymphoma |
Linfoma di Hodgkin e Linfoma Non-Hodgkin |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080208 |
E.1.2 | Term | Classical Hodgkin lymphoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025322 |
E.1.2 | Term | Lymphomas non-Hodgkin's unspecified histology |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025320 |
E.1.2 | Term | Lymphomas non-Hodgkin's B-cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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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 |
Part A: To characterize the safety, tolerability, and define the MTD or RP2D for the combination of relatlimab + nivolumab in pediatric participants less than 18 years of age with R/R cHL and NHL. Part A: To characterize the PK of relatlimab for the combination of relatlimab + nivolumab in pediatric participants less than 18 years of age with R/R cHL and NHL. Part B: To assess the preliminary efficacy of relatlimab + nivolumab based on the RP2D from part A in participants less than or equal to 30 years old with cHL (Cohort 1). |
Parte A: caratterizzare la sicurezza e la tollerabilità, nonché definire la MTD o la RP2D per la combinazione di relatlimab + nivolumab in partecipanti pediatrici di età inferiore a 18 anni con cHL e LNH R/R. Parte A: caratterizzare la PK di relatlimab per la combinazione di relatlimab + nivolumab in partecipanti pediatrici di età inferiore a 18 anni con cHL e LNH R/R. Parte B: valutare l’efficacia preliminare di relatlimab + nivolumab in base alla RP2D della Parte A in partecipanti di età inferiore o uguale a 30 anni con cHL (Coorte 1). |
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E.2.2 | Secondary objectives of the trial |
Part B: To assess the safety of relatlimab + nivolumab in R/R cHL (Cohort 1) and NHL (Cohort2) Part B: To evaluate the ORR of relatlimab + nivolumab in participants <= 30 years of age with cHL (Cohort 1) |
Parte B: valutare la sicurezza di relatlimab + nivolumab nel cHL (Coorte 1) e LNH (Coorte 2) R/R. Parte B: valutare l’ORR di relatlimab + nivolumab in partecipanti di età <= 30 anni con cHL (Coorte 1). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female participants less than 18 years of age (Part A), and less than or equal to 30 years of age (Part B) with Recurrent or Refractory Classical Hodgkin Lymphoma (R/R cHL) (Cohort 1) and Non Hodgkin Lymphoma (NHL) (Cohort 2). • Participants with pathologically confirmed high-risk R/R cHL, after non-response to or failure of first-line standard therapy prior to HDCT/ASCT. • Participants with pathologically confirmed high-risk, R/R NHL after failure or non-response to first-line therapy • Participants must have measurable FDG-PET-CT positive disease in both cHL and NHL cohorts. |
• Partecipanti di sesso maschile e femminile di età inferiore a 18 anni (Parte A) e di età pari o inferiore a 30 anni (Parte B) con cHL (Coorte 1) e LNH (Coorte 2) R/R. • Partecipanti con cHL R/R ad alto rischio confermato patologicamente, dopo mancata risposta o fallimento della terapia standard di prima linea prima di HDCT/ASCT. • Partecipanti con LNH R/R ad alto rischio confermato patologicamente dopo fallimento o mancata risposta alla terapia di prima linea • I partecipanti devono presentare malattia positiva alla FDG-PET-TC misurabile in entrambe le coorti cHL e LNH. |
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E.4 | Principal exclusion criteria |
• Prior treatment with an anti-cytotoxic T-lymphocyte-associated protein 4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways, with the exception of anti-PD(L)-1 targeted therapies. • Prior treatment with LAG-3-targeted agents. • Participants with prior autologous stem cell transplantation (HDCT/ASCT). • Participants with a history of allogeneic bone marrow transplantation and with active graft versus host disease (GVHD) and prior history of Grade > 2 GVHD. • Participants with clinically significant systemic illnesses unrelated to the cancer as judged by the investigators, which would compromise the participant's ability to tolerate the study treatment. • Participants with autoimmune disease. |
• Precedente trattamento con un anticorpo anti-proteina 4 associata ai linfociti T citotossici o qualsiasi altro anticorpo o farmaco specificamente mirato alla co-stimolazione delle cellule T o ai pathway del checkpoint, ad eccezione delle terapie mirate anti-PD(L)-1. • Precedente trattamento con agenti mirati a LAG-3. • Partecipanti con precedente trapianto autologo di cellule staminali (HDCT/ASCT). • Partecipanti con anamnesi di trapianto allogenico di midollo osseo e con malattia del trapianto contro l’ospite (GVHD) attiva e anamnesi pregressa di GVHD di grado >2. • Partecipanti con malattie sistemiche clinicamente significative non correlate al tumore secondo il giudizio degli sperimentatori, che comprometterebbero la capacità del partecipante di tollerare il trattamento dello studio. • Partecipanti con malattia autoimmune. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1/Part A- Dose-limiting toxicities (DLTs), Maximum Tolerated Dose/Recommended Phase 2 Dose; (MTD/RP2D), and incidences of Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to discontinuation, deaths and laboratory abnormalities 2/Part A- maximum observed serum concentration (Cmax), trough observed concentration (Ctrough), time to maximum concentration (Tmax), and area under the curve within a dosing interval (AUC(TAU)) for relatlimab 3/Part B- Complete Metabolic Response (CMR) rate |
1/ Parte A: tossicità dose-limitante (DLT), Dose Massima Tollerata/Dose raccomandata per la Fase 2 (MTD/RP2D) e incidenze di Eventi Avversi (EA), Eventi avversi gravi (SAE) ed EA che portano all’interruzione del trattamento, al decesso e ad anomalie di laboratorio 2/ Parte A: concentrazione sierica massima osservatao(Cmax), Concentrazione minima osservata (Cmin), tempo alla concentrazione massima (Tmax) es area sotto la curva entro l'intervallo di dosaggio AUC(TAU) per relatlimab 3/ Parte B: Tasso di Risposta metabolica completa (RMC) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1/Up to 100 days after the last dose of study Treatment 2/At specified timepoints in Section 9.5 of the protocol 3/Up to 32 weeks from last patient first treatment |
1/ Fino a 100 giorni dopo l'ultima dose di trattamento in studio 2/ Agli specifici tempi come nella sezione 9.5 del protocollo 3/ Fino a 32 settimane dopo il primo trattamento dell'ultimo paziente |
|
E.5.2 | Secondary end point(s) |
1/Part B: Incidences of AEs, SAEs, AEs leading to discontinuation, deaths, and laboratory abnormalities 2/Part B: Overall Response Rate (ORR) |
1/ Parte B: incidenze di Eventi Avversi (EA), Eventi avversi gravi (SAE) ed EA che portano all’interruzione del trattamento, al decesso e ad anomalie di laboratorio 2/ Parte B: Tasso di risposta totale |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/Up to 100 days after the last dose of study Treatment 2/Up to 2 years after LPFT |
1/ Fino a 100 giorni dopo l'ultima dose di trattamento in studio 2/ Fino a 2 anni dopo il primo trattamento dell'ultimo paziente |
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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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tollerabilità |
|
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 |
Dose-finding cohort by age/weight group |
individuazione della dose per coorte di età/peso |
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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 | 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 | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
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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
|
The last participant last visit in the survival follow-up period |
LVLS nel periodo di follow-up di sopravvivenza |
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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 | 7 |
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 | 7 |
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 |