E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hodgkin’s Lymphoma |
Linfoma di Hodgkin |
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E.1.1.1 | Medical condition in easily understood language |
Hodgkin’s Lymphoma |
Linfoma di Hodgkin |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10005329 |
E.1.2 | Term | Blood and lymphatic system disorders |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the activity of brentuximab vedotin in terms of complete remission (CT scan and FDG-PET negative) in patients with relapsed/refractory Hodgkin’s Lymphoma not responding (FDG-PET positive) to salvage treatment with IGEV. |
Valutare l'attività di brentuximab vedotin in termini di remissione completa (TC scan e FDG-PET negativa) in pazienti affetti da Linfoma di Hodgkin recidivato o refrattario non rispondenti (FDG-PET positiva) alla terapia di salvataggio con IGEV. |
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E.2.2 | Secondary objectives of the trial |
To evaluate if brentuximab vedotin administration after unsatisfactory response to IGEV is able to achieve CR, thus improving progression free survival (PFS) and duration of remission.
To evaluate the toxicity of brentuximab vedotin in terms of haematological and extra-haematological side effects according to the NCI CTCAE (Version 4.03).
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Valutare se la somministrazione di brentuximab vedotin dopo la risposta insoddisfacente a IGEV è in grado di raggiungere una risposta completa (RC), migliorando così la sopravvivenza libera da progressione (PFS) e la durata della remissione. Valutare la tossicità di brentuximab vedotin in termini di effetti collaterali ematologici ed extra-ematologiche secondo il NCI CTCAE (versione 4.03). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Classical Hodgkin Lymphoma according to the World Health Organisation (WHO) classification 2. Histologically confirmed CD30+ HL at diagnosis 3. Patients at the first line salvage therapy 4. FDG-PET positivity after two cycles of IGEV treatment 5. PBPCs should have been collected after the first or the second IGEV cycle 6. Age≥ 18 years 7. ECOG performance status of 0-2 8. Life expectancy > 6 months. 9. Written informed consent was obtained from the patient prior to any study-specific screening procedures 10. Patients must be available for periodic blood sampling, study-related assessments and management of toxicity at the treating institution 11. Females of childbearing potential must have a negative β-HCG pregnancy test result (pregnancy test should be performed at screening an on day 1 of cycle 1 prior to brentuximab vedotin treatment). 12. Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
13. Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse. 14. Required baseline laboratory data: - Absolute neutrophil count ≥ 1500/µl - Platelet count ≥ 75.000/ µl - Haemoglobin must be ≥ 8 g/dL - Serum bilirubin ≤ 1.5 times ULN - Serum creatinine < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute. - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN
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1. Linfoma di Hodgkin a istologia classica secondo la classificazione WHO. 2. Histologically confirmed CD30+ HL at diagnosis 3. Pazienti alla prima linea di terapia di salvataggio. 4. FDG-PET positive dopo 2 cicli di trattamento con IGEV 5. PBPCs raccolte dopo il primo o il secondo ciclo di IGEV. 6. Età ≥ 18 7. ECOG performance status 0-2 8. Aspettativa di vita > 6 mesi 9. Firma del consenso informato prima di effettuare le procedure di screening studio specifiche. 10. I pazienti dovranno essere disponibili per i periodici prelievi di sangue, la valutazione e la gestione della tossicità presso l’ospedale che li ha in cura. 11. Le donne in età fertile dovranno effettuare un test di gravidanza che dovrà risultare β-HCG negativo (il test dovrà essere effettuato allo screening e al giorno 1 del ciclo 1 prima della somministrazione di Brentuximab vedotin. 12. Donne in menopausa da almeno 1 anno prima della visita di screening o rese chirurgicamente sterili o donne in età fertile che si impegnano a utilizzare almeno 2 metodi contraccettivi considerati efficaci dalla firma del consenso informato fino a 6 mesi dopo l’ultima somministrazione del farmaco in studio o donne che si impegnano ad astenersi completamente dai rapporti eterosessuali. 13. Pazienti di sesso maschile, anche se resi chirurgicamente sterili (stato di post vasectomia) che si impegnano a utilizzare un efficace contraccettivo a barrier durante tutta la durata dello studio e fino a 6 mesi dopo l’ultima somministrazione del farmaco in studio o pazienti di sesso maschile che si impegnano ad astenersi completamente da rapporto eterosessuali. 14. Al baseline richiesti i seguenti valori di laboratorio: - Conta assoluta dei neutrofili ≥ 1500/µl - Conta piastrinica ≥ 75.000/ µl - Emoglobina ≥ 8 g/dL - Bilirubina sierica ≤ 1.5 times ULN - Creatinine < 2.0 mg/dL e/o creatinine clearance o creatinine clearance calcolata > 40 mL/minute. - ALT e AST ≤ 2.5 times ULN
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E.4 | Principal exclusion criteria |
1. Peripheral neuropathy > Grade 1 2. Histologic diagnosis different from Hodgkin Lymphoma 3. First line treatment with BEACOPP 4. Compressive symptoms caused by the presence of Lymphoma 5. Patients who have been treated previously with any anti-CD30 antibody. 6. Known hypersensitivity to any recombinant proteins, murine proteins, or excipients contained in the brentuximab vedotin formulation. 7. Known human immunodeficiency virus (HIV) positive 8. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection 9. Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 10. Patients with known history of any of the following cardiovascular conditions : • Myocardial infarction within 2 years of randomization • New York Heart Association (NYHA) Class III or IV heart failure (see Appendix E) • Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities • Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50% 11. Patients with known active viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy within 2 weeks prior to the first dose of brentuximab vedotin. 12. Patients with known active Grade 3 or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of brentuximab vedotin. 13. Patients with known cerebral/meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencephalopathy (PML). 14. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to protocol. 15. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications. 16. Patients who are pregnant, or lactating and breastfeeding. 17. Patients that have not completed any prior treatment chemotherapy and/or other investigational agents within at least 5 half-lives of last dose of that prior treatment. |
1. Neuropatia periferica > grado 1 2. Diagnosi istologica diversa da Linfoma di Hodgkin 3. Prima linea di trattamento con BEACOPP 4. Sintomi da compressione causati dalla presenza del linfoma 5. Pazienti trattati precedentemente con anticorpo anti-CD30 6. Nota ipersensibilità a qualsiasi proteina ricombinante, proteine murine, o eccipienti contenuti nella formulazione di Brentuximab vedotin. 7. Pazienti HIV positivi 8. Epatite B nota HBsAg + o sospetta infezione da epatite C attiva. 9. Altra neoplasia diagnosticata o trattata nei 3 anni precedenti l’inizio della terapia o neoplasia diagnosticata in precedenza con evidenza di malattia residua. Non vengono esclusi i pazienti con tumori della pelle (non melanoma) o carcinoma in situ sottoposti a resezione completa. 10. Pazienti con anamnesi di una qualsiasi delle seguenti condizioni cardiovascolari: - Infarto del miocardio entro 2 anni - Insufficienza cardiac di classe III o IV secondo la classificazione New York Heart Association (NYHA) (see Appendix E) - Evidenza di condizioni cardiovascolari non controllate incluse aritmie cardiache, insufficienza cardiaca congestizia (CHF), angina, o evidenza elettrocardiografica di ischemia acuta o anomalie attive del sistema di conduzione. - Recenti evidenze (entro 6 mesi dalla somministrazione della prima dose del farmaco in studio) di una frazione di eiezione ventricolare sinistra <50%. 11. Pazienti con infezione virale, batterica o fungina attiva che richiede un trattamento con terapia antibiotica entro 2 settimane precedenti alla prima dose di Brentuximab vedotin. 12. I pazienti infezione attiva virale, batterica o fungina di grado superiore o uguale a 3 entro 2 settimane precedenti alla prima dose di Brentuximab vedotin. 13. I pazienti con nota malattia cerebrale / meningea (HL o qualsiasi altra eziologia), compresi i segni o i sintomi di leucoencefalopatia multifocale progressiva (PML). 14. Qualsiasi grave malattia medica o psichiatrica che potrebbe, a giudizio dello sperimentatore, potenzialmente interferire con il completamento del trattamento secondo il protocollo. 15. Malattia neurologica sintomatica che compromette le normali attività della vita quotidiana o che richiede l’utilizzo di farmaci. 16. Pazienti in gravidanza o in fase di allattamento 17. Pazienti che non hanno completato qualsiasi trattamento chemioterapico precedente e/o altra terapia sperimentale da almeno 5 volte l’emivita dell’ultima dose di tale trattamento.
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 year and half from the beginning of the study |
1 anno e mezzo dall’inizio dello studio |
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E.5.2 | Secondary end point(s) |
Toxicity and PFS |
Tossicità e PFS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Toxicity: 1 year and half from the beginning of the study PFS: 2 years and half from the beginning of the study |
La tossicità va pari alla risposta (valutazione finale dello studio dopo 1 anno e mezzo dall’'inizio dello studio). PFS dopo circa 2.5 anni dall’inizio dello studio. |
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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 | 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.8.3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |