E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent or Refractory pediatric cancer |
Neoplasie maligne pediatriche ricorrenti o refrattarie |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent or Refractory Pediatric Malignancies |
Neoplasie maligne pediatriche ricorrenti o resistenti al trattamento |
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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 | PT |
E.1.2 | Classification code | 10029260 |
E.1.2 | Term | Neuroblastoma |
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 | PT |
E.1.2 | Classification code | 10015560 |
E.1.2 | Term | Ewing's sarcoma |
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 | PT |
E.1.2 | Classification code | 10039022 |
E.1.2 | Term | Rhabdomyosarcoma |
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 | LLT |
E.1.2 | Classification code | 10049280 |
E.1.2 | Term | Solid tumour |
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 | 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 |
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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 | 10024329 |
E.1.2 | Term | Leukemia |
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065443 |
E.1.2 | Term | Malignant glioma |
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 | PT |
E.1.2 | Classification code | 10027107 |
E.1.2 | Term | Medulloblastoma |
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 | PT |
E.1.2 | Classification code | 10014967 |
E.1.2 | Term | Ependymoma |
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 | 10007958 |
E.1.2 | Term | Central nervous system neoplasm |
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 |
Primary - Part A Safety Lead-in:
- Safety Lead-in: To estimate the safety and tolerability of study treatment in pediatric participants with malignant neoplasms that are refractory, relapsed, or participants for whom curative treatments are lacking.
- To characterize the pharmacokinetics (PK) of bempegaldesleukin and nivolumab in pediatric participants with malignant neoplasms that are refractory, relapsed, or participants for whom curative treatments are lacking.
Primary - Part B Expansion
To estimate the preliminary efficacy (eg, ORR of study treatment separately in the following disease cohorts):
B1: Neuroblastoma
B2: Ewing sarcoma
B3: Rhabdomyosarcoma
B4: Miscellaneous solid tumors
B5: Non-Hodgkin lymphoma (NHL)/leukemia ¿
B6: High-grade glioma
B7: Medulloblastoma and embryonal tumors ¿
B8: Ependymoma
B9: Miscellaneous central nervous system (CNS) tumors |
Primario - Parte A Lead-in di sicurezza • Lead-in di sicurezza: Stimare la sicurezza e la tollerabilità del trattamento dello studio nei partecipanti pediatrici con neoplasie maligne refrattarie, recidivanti o nei partecipanti per i quali mancano trattamenti curativi. • Caratterizzare la farmacocinetica (PK) di bempegaldesleukin e nivolumab nei partecipanti pediatrici con neoplasie maligne refrattarie, recidivanti o nei partecipanti per i quali mancano trattamenti curativi. Primario - Parte B Espansione • Stimare l’efficacia preliminare (ad es., l’ORR [tasso di risposta obiettivo] del trattamento dello studio separatamente nelle seguenti coorti di malattia): o B1: neuroblastoma o B2: sarcoma di Ewing o B3: rabdomiosarcoma o B4: vari tumori solidi o B5: linfoma non-Hodgkin (LNH)/leucemia o B6: glioma di alto grado o B7: medulloblastoma e tumori embrionali o B8: ependimoma o B9: vari tumori del sistema nervoso centrale (SNC) |
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E.2.2 | Secondary objectives of the trial |
Secondary - Part B Expansion
- To estimate the safety of study therapy in pediatric participants.
- To estimate the progression-free survival (PFS) and overall survival (OS) of study therapy in pediatric participants. |
Secondario - Parte B Espansione • Stimare la sicurezza della terapia dello studio nei partecipanti pediatrici. • Stimare la PFS (sopravvivenza libera da progressione) e la OS (sopravvivenza complessiva) della terapia dello studio nei partecipanti pediatrici |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetics Version: CA045020/19-214-27 Date: 08/10/2020 Title: CLINICAL PROTOCOL CA045020/19-214-27 Phase 1/2 Study of Bempegaldesleukin in Combination with Nivolumab in Children, Adolescents, and Young Adults with Recurrent or Refractory Malignancies (PIVOT IO 020) Sez. 9.8.1 Additional Research Collection Objectives: Sez. 9.8.1 Additional Research Collection
Pharmacogenomics Version: CA045020/19-214-27 Date: 08/10/2020 Title: CLINICAL PROTOCOL CA045020/19-214-27 Phase 1/2 Study of Bempegaldesleukin in Combination with Nivolumab in Children, Adolescents, and Young Adults with Recurrent or Refractory Malignancies (PIVOT IO 020) Sez. 9.8.1 Additional Research Collection Objectives: Sez. 9.8.1 Additional Research Collection
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Farmacogenetica Versione: CA045020/19-214-27 Data: 08/10/2020 Titolo: PROTOCOLLO CLINICO CA045020/19-214-27 Studio di fase 1/2 su Bempegaldesleukin in combinazione con Nivolumab in bambini, adolescenti e giovani adulti con neoplasie maligne ricorrenti o refrattarie (PIVOT IO 020) Sezione. 9.8.1 Raccolta per la Ricerca addizionale Obiettivi: Sezione. 9.8.1 Raccolta per la Ricerca addizionale
Farmacogenomica Versione: CA045020/19-214-27 Data: 08/10/2020 Titolo: PROTOCOLLO CLINICO CA045020/19-214-27 Studio di fase 1/2 su Bempegaldesleukin in combinazione con Nivolumab in bambini, adolescenti e giovani adulti con neoplasie maligne ricorrenti o refrattarie (PIVOT IO 020) Sezione. 9.8.1 Raccolta per la Ricerca addizionale Obiettivi: Sezione. 9.8.1 Raccolta per la Ricerca addizionale
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E.3 | Principal inclusion criteria |
- Age < 18 years for Part A and Part B
- Age up to 30 years for Part B Cohorts B2, B3 and B4
- Must have received standard of care therapy and there must be no potentially curative treatment available
- Histologically confirmed with malignant neoplasms that are refractory, relapsed, or curative treatments are lacking
- Must have measurable or evaluable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for solid tumors, Response Assessment in Neuro-Oncology (RANO) or Response Assessment in Pediatric Neuro-Oncology (RAPNO) for central nervous system tumors, International Pediatric Non-Hodgkin Lymphoma Response Criteria for non-Hodgkin lymphoma (NHL), revised International Neuroblastoma Response Criteria (INRC) for neuroblastoma, modified National Comprehensive Cancer Network (NCCN) Criteria for acute lymphoblastic leukemia, and modified Cheson et al International Working Group criteria for acute myeloid leukemia
- Lansky play score for age = 16 years or Karnofsky performance score for age > 16 years assessed within 2 weeks of enrollment must be = 60 |
• Età inferiore a 18 anni a per la Parte A e la Parte B. • Età sino a 30 anni per la Parte B Coorti B2, B3 e B4 • I partecipanti devono aver ricevuto la terapia standard e non deve essere disponibile alcun trattamento potenzialmente curativo. • Neoplasie maligne, confermate istologicamente, recidivanti o refrattarie, o per cui mancano trattamenti curativi • I partecipanti devono presentare malattia misurabile o valutabile in base ai Response Evaluation Criteria in Solid Tumors RECIST v1.1 per i tumori solidi, Response Assessment in Neuro-Oncology (RANO) o Response Assessment in Pediatric Neuro-Oncology (RAPNO) per i tumori del SNC, International Pediatric NonHodgkin Lymphoma Response Criteria per Lnforma non –Hodgkin (LNH), International Neuroblastoma Response Criteria (INCR) revisionati per il neuroblastoma, National Comprehensive Cancer Network Criteria (NCCN) modificati per la leucemia linfoblastica acuta e Cheson et al International Working Group Criteria modificati per la leucemia mieloide acuta. • Il punteggio di Lansky relativo alle attività di gioco per partecipanti di età =16 anni o il punteggio della scala di Karnofsky per partecipanti di età >16 anni, valutato entro 2 settimane dall’arruolamento, deve essere =60. |
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E.4 | Principal exclusion criteria |
- Osteosarcoma, T-cell/NK-cell leukemia/lymphoma, and Hodgkin lymphoma
- Need for > 2 antihypertensive medications for management of hypertension (including diuretics)
- Known cardiovascular history, including unstable or deteriorating cardiac disease, within the previous 12 months prior to screening
- Inadequately treated adrenal insufficiency
- Active, known, or suspected autoimmune disease
- Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment
- Prior allogeneic stem cell transplant
- Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either suspected or confirmed within 4 weeks prior to screening |
• Osteosarcoma, leucemia/linfoma a cellule T/cellule Natural Killer e linfoma di Hodgkin • Necessità di >2 farmaci antipertensivi per la gestione dell’ipertensione (compresi i diuretici) • Anamnesi cardiovascolare nota, inclusa malattia cardiaca instabile o in peggioramento, nei 12 mesi precedenti lo screening • Insufficienza surrenalica non trattata adeguatamente • Patologia che richiede il trattamento sistemico con corticosteroidi o altri farmaci immunosoppressori nei 14 giorni precedenti l’inizio del trattamento dello studio • Precedente trapianto allogenico di cellule staminali • Precedente infezione da SARS-CoV-2 (sindrome respiratoria acuta grave Coronavirus-2), sospetta o confermata, nelle 4 settimane precedenti lo screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A:
1. Incidence of dose-limiting toxicities, adverse events (AEs), serious AEs (SAEs), drug-related AEs, AEs leading to discontinuation and death.
2. Pharmacokinetic (PK) parameters: Peak concentration, trough concentration, time-averaged concentration, clearance (CL) and volume of distribution (Vd).
Part B:
3. Investigator-assessed objective response rate (ORR) |
Parte A: 1) Incidenza di tossicità dose-limitanti, eventi avversi (EA), EA seri (EAS), EA correlati al farmaco, EA che portano all’interruzione e al decesso 2) Parametri PK: picco di concentrazione, concentrazione minima, concentrazione media nel tempo, clearance (CL) e volume di distribuzione (Vd) Parte B 3) Tasso di risposta obiettiva valutato dallo sperimentatore |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 2 years and 100 days
2. Up to 2 years
3. Up to 5 years |
1) Fino a 2 anni e 100 giorni 2) Fino a 2 anni 3) Fino a anni |
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E.5.2 | Secondary end point(s) |
Part B:
- Incidence of AEs, SAEs, drug-related AEs, AEs leading to discontinuation and death.
- Incidence of laboratory abnormalities: Hematology tests and clinical chemistry tests.
- Progression-free survival (PFS)
- Overall survival (OS) |
Parte B • Incidenza di eventi avversi (EA), eventi avversi seri (EAS), EA correlati al farmaco, EA che determinano interruzione del trattamento e decesso. • Incidenza di anomalie di laboratorio: ematologici e chimici • Sopravvivenza libera da progressione (PFS) • Sopravvivenza complessiva (OS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 5 years |
Fino a 5 anni |
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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 | Yes |
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 | 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) | 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 |
Phase IB - Dose-finding study design |
fase 1b (dose finding) |
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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 | 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 | 13 |
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 | 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 | 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 |
United States |
France |
Germany |
Italy |
Netherlands |
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 |
LVLS (ultima visita dell’ultimo soggetto) |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 10 |