| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Classical Hodgkin Lymphoma |
| Linfoma di Hodgkin classico |
|
| E.1.1.1 | Medical condition in easily understood language |
| Hodgkin Lymphoma |
| Linfoma di Hodgkin |
|
| 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 | LLT |
| E.1.2 | Classification code | 10020328 |
| E.1.2 | Term | Hodgkin's lymphoma |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020328 |
| E.1.2 | Term | Hodgkin's lymphoma |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
| Parts B and C: To assess the complete response (CR) rate at EOT with AN+AD in subjects with previously untreated cHL |
| Parti B e C: Valutare il tasso di risposta completa (CR) a fine trattamento (EOT) con AN+AD in soggetti con linfoma di Hodgkin classico (cHL) precedentemente non trattato |
|
| E.2.2 | Secondary objectives of the trial |
Parts B and C:
To assess the safety and tolerability of AN+AD
- To assess the overall response rate (ORR)
- To assess the duration of response (DOR)
- To assess the duration of complete response (DOCR)
- To assess the event-free survival (EFS)
- To assess the progression-free survival (PFS)
- To assess the overall survival (OS) |
Parti B e C:
- Valutare la sicurezza e la tollerabilità di AN+AD
- Valutare il tasso di risposta complessiva (ORR)
- Valutare la durata della risposta (DOR)
- Valutare la durata della risposta completa (DOCR)
- Valutare la sopravvivenza libera da eventi (EFS)
- Valutare la sopravvivenza libera da progressione (PFS)
- Valutare la sopravvivenza complessiva (OS) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Treatment-naïve, cHL subjects:
a. Subjects enrolling in Part B of the study must have Ann Arbor Stage I or II cHL with bulky mediastinal disease, or Stage III or IV disease.
b. Subjects enrolling in Part C of the study must have Ann Arbor Stage I or II cHL without bulky mediastinal disease.
• Histologically confirmed cHL according to the current World Health
Organization Classification.
• Bidimensional measurable disease as documented by PET/CT or CT imaging.
• Age 12 years or older in the United States. For regions outside of the United States, subjects must be age 18 years or older.
• An Eastern Cooperative Oncology Group (ECOG) performance status < = 2.
Other protocol defined inclusion criteria may apply. |
• Soggetti con cHL naïve al trattamento:
a. I soggetti che si arruolano nella Parte B dello studio devono presentare cHL allo stadio di Ann Arbor I o II, con malattia massiva del mediastino o malattia allo stadio III o IV.
b. I soggetti che si arruolano nella Parte C dello studio devono presentare cHL allo stadio di Ann Arbor I o II senza malattia massiva del mediastino.
• cHL istologicamente confermato secondo l’attuale Classificazione dell’Organizzazione Mondiale della Sanità.
• Malattia misurabile bidimensionale documentata mediante PET/TC o TC.
• Età pari o superiore a 12 anni negli Stati Uniti. Per le regioni al di fuori degli Stati Uniti, i soggetti devono avere un’età pari o superiore a 18 anni.
• Stato di performance secondo l’Eastern Cooperative Oncology Group (ECOG) <= 2.
Potrebbero applicarsi criteri di inclusione aggiuntivi definiti dal protocollo. |
|
| E.4 | Principal exclusion criteria |
• Nodular lymphocyte predominant HL
• History of another malignancy within 3 years before the first dose of study drug or any evidence of residual disease from a previously
diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death. Subjects with nonmelanoma skin cancer,
localized prostate cancer, or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 4 weeks of first study drug dose.
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or antiCTLA-4 antibody, or any other antibody or drug specifically targeting Tcell
co-stimulation or checkpoint pathways.
• Active cerebral/meningeal disease related to the underlying malignancy.
• Any active Grade 3 or higher (per the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] Version
4.03) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study drug.
• Current therapy with other systemic anti-neoplastic or investigational agents.
• Planned consolidative radiotherapy during the study treatment period (Parts B and C only).
• Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary
toxicity (Parts B and C only).
• Grade 3 or higher pulmonary disease unrelated to underlying malignancy.
• Idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon monoxide <50% predicted.
• Documented history of a cerebral vascular event within 6 months prior to their first dose of brentuximab vedotin.
• Subjects with Child-Pugh B or C hepatic impairment.
• Grade 2 or higher peripheral sensory or motor neuropathy at baseline.
• Subjects with acute or chronic graft-versus-host-disease (GvHD) or receiving immunosuppressive therapy as treatment for or prophylaxis
agent against GvHD.
• Previous treatment with brentuximab vedotin.
• Subjects who are pregnant or breastfeeding.
Other protocol defined exclusion criteria may apply. |
• LH predominante dei linfociti nodulari:
• Anamnesi di altra malignità nei 3 anni precedenti la prima dose del farmaco in studio o qualsiasi evidenza di malattia residua da una malignità precedentemente diagnosticata. Costituiscono eccezioni le malignità con un rischio trascurabile di metastasi o decesso. I soggetti con carcinoma cutaneo non melanoma, carcinoma prostatico localizzato o carcinoma in situ di qualsiasi tipo non sono esclusi se sono stati sottoposti a resezione completa.
• Precedente chemioterapia immunosoppressiva, radiazione terapeutica o qualsiasi immunoterapia entro 4 settimane dalla prima dose di farmaco dello studio
• Precedente trattamento con un anticorpo anti-proteina di morte programmata-1 (anti-PD-1), anti-ligando 1 della proteina di morte cellulare programmata (anti-PD-L1), anti-ligando 2 della proteina di morte cellulare programmata (anti-PD-L2) o anti-proteina 4 associata ai linfociti T citotossici (anti-CTLA-4) o qualsiasi altro anticorpo o farmaco specificamente mirato alla co-stimolazione delle cellule T o ai pathway del checkpoint
• Malattia cerebrale/meningea attiva correlata alla malignità sottostante.
• Qualsiasi infezione virale, batterica o fungina attiva di Grado 3 o superiore (secondo i Criteri terminologici comuni per gli eventi avversi del National Cancer Institute [NCI CTCAE] versione 4.03) entro le 2 settimane precedenti la prima dose di farmaco dello studio.
• Attuale terapia con altri agenti antineoplastici sistemici o sperimentali.
• Radioterapia consolidativa programmata durante il periodo di trattamento dello studio (solo Parti B e C).
• Malattia polmonare interstiziale attiva sintomatica o che può interferire con il rilevamento o la gestione di sospetta tossicità polmonare correlata al farmaco (solo Parti B e C).
• Malattia polmonare di Grado 3 o superiore non correlata a malignità sottostante.
• Polmonite interstiziale idiopatica o capacità di diffusione del polmone per il monossido di carbonio <50% prevista.
• Anamnesi documentata di evento cerebrovascolare nei 6 mesi precedenti la prima dose di brentuximab vedotin.
• Soggetti con compromissione epatica secondo Child-Pugh B o C.
• Neuropatia sensoriale periferica o motoria di Grado 2 o superiore al basale.
• Soggetti con malattia da trapianto contro l’ospite (GvHD) cronica o acuta o che ricevono una terapia immunosoppressiva come trattamento o un agente di profilassi contro la GvHD.
• Precedente trattamento con brentuximab vedotin.
• Soggetti in gravidanza o in fase di allattamento al seno.
Potrebbero applicarsi criteri di esclusione aggiuntivi definiti dal protocollo. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| CR rate at EOT |
| Percentuale della CR all’EOT |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Fino a 6 mesi |
| Up to 6 months |
|
| E.5.2 | Secondary end point(s) |
- Incidence, severity, seriousness, and relatedness of AEs; incidence and severity of lab abnormalities
- Estimate the ORR
- DOR
- DOCR
- EFS
- PFS |
- Incidenza, gravità, serietà e correlazione degli eventi avversi (EA); incidenza e gravità delle anomalie di laboratorio
- Stimare l’ORR
- DOR
- DOCR
- EFS
- PFS |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Up to 7 months
- Up to 6 months
- Up to 5 years
- Up to 5 years
- Up to 5 years
- Up to 5 years
- Up to 5 years |
- Fino a 7 mesi
- Fino a 6 mesi
- Fino a 5 anni
- Fino a 5 anni
- Fino a 5 anni
- Fino a 5 anni
- Fino a 5 anni |
|
| 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 | No |
| 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 | 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 | 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 | 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 | 15 |
| 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 |
| Canada |
| United States |
| Italy |
| Spain |
|
| 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
|
| The study will be closed approximately 5 years after the last subject receives the last dose, or when no subjects remain in follow-up, whichever occurs first |
| Lo studio verrà chiuso circa 5 anni dopo che l'ultimo soggetto ha ricevuto l'ultima dose, o quando nessun soggetto rimane nel follow-up, a seconda di quale condizione si verifica per prima |
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| 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 |
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