E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
marginal zone B-cell lymphomas (MZL) |
linfoma marginale di tipo B |
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E.1.1.1 | Medical condition in easily understood language |
marginal zone B-cell lymphomas (MZL) |
linfoma marginale di tipo B |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029463 |
E.1.2 | Term | Nodal marginal zone B-cell lymphoma recurrent |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029464 |
E.1.2 | Term | Nodal marginal zone 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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy (Overall Remission Rate) of ofatumumab and bendamustine in relapsed or refractory marginal zone B-cell lymphomas |
Valutare la percentuale di risposta (Overall Remission Rate, ORR) della combinazione bendamustina e ofatumumab in pazienti con linfoma marginale di tipo B refrattario o ricaduto |
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E.2.2 | Secondary objectives of the trial |
- Duration of antitumor activity - Safety profile - Feasibility of the combination |
- Durata dell'attività antitumorale - Profilo di sicurezza - Fattibilità della combinazione |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age > 18 2. Histologically proven diagnosis of marginal zone B-cell lymphoma relapsing/refractory following at least 1 prior systemic treatment (chemotherapy and/or monoclonal antibodies) 3. Any stage (Ann Arbor I-IV) 3. Life expectancy of at least 6 months and ECOG performance status 0-1 4. No evidence of histological transformation to diffuse large cells lymphoma 5. Adeguate bone marrow function, renal function or liver function 6. Signed informed consent |
• Età > 18 anni • Istologia di linfoma marginale a cellule B refrattario o ricaduto dopo almeno un precedente trattamento sistemico (chemioterapia o anticorpi monoclonali). • Aspettativa di vita di almeno 6 mesi ed ECOG performance status 0-1 • Nessuna evidenza di trasformazione istologica a linfoma diffuso a grandi cellule • Adeguata funzionalità renale, midollare ed epatica • Firma del consenso informato |
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E.4 | Principal exclusion criteria |
1. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment 2. Treatment with anti-CD20 monoclonal antibody or alemtuzumab within 8 weeks prior to the enrollment 3. Treatment with corticosteroids during the last 4 weeks 4.Other past or current malignancy 5. Previous organ transplantation 6.Clinically significant cardiac or pulmonary disease 7.History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequele 8. Concomitant infectious diseases, HIV positive, Hepatitis B or C positive. |
• Altro trattamento sperimentale nelle 4 settimane prima dell’arruolamento • Trattamento con un anticorpo monoclonale anti-CD20 o alemtuzumab entro le ultime 8 settimane • Trattamento con corticosteroidi nelle ultime 4 settimane • Presenza di altre patologie tumorali • Precedente trapianto d’organo • Malattia cardiaca o polmonare clinicamente rilevanti • Malattie cerebrovascolari nei precedenti 6 mesi o presenti al momento dell’arruolamento con sintomi o sequelae • Infezioni concomitanti, positività HIV, positività e epatite B o C |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate (CR+PR), defined according to Cheson criteria (Cheson et al 2007). For patients with splenic MZL response is defined according to Matutes et al. 2008 and for patients with gastric lymphomas histological response is evaluated according to GELA scoring system (Copie-Bergman et al 2003) |
Tasso di risposta complessivo (ORR = CR+PR), secondo i criteri di Cheson (Cheson et al 2007). Per i pazienti con MZL della milza la risposta è definita secondo Matutes et al. 2008 e per i pazienti con linfoma gastrico la risposta istologica è valutata secondo il GELA scoring system (Copie-Bergman et al 2003) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
CT-scan at the end of cycle 2 and at F-up 1 (4 mos), F-up 2 (8 mos) e F-up 3 (24 mos) after the end of treatment. |
Valutazione radiologica (CT-scan) alla fine del secondo ciclo e ai F-up 1 (4 mesi), F-up 2 (8 mesi) e F-up 3 (24 mesi) dalla fine del trattamento. |
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E.5.2 | Secondary end point(s) |
- Two years Progression Free Survival (PFS) - Time to next treatment - Adverse events according to NCI-CTC V3 |
- Sopravvivenza libera da progressione (PFS) a 2 anni - Tempo mediano alla successiva terapia - Durata mediana della risposta - Eventi avversi secondo NCI-CTC V3 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- PFS: 2 years after the end of the treatment. - Time to next treatment. - Time to relapse. - Continuous evaluation of AE. |
- Due anni dalla fine del trattamento per la valutazione della sopravvivenza. - Tempo al quale si rende necessaria una nuova terapia. - Tempo al quale si manifesta la ricaduta (o progressione o morte per qualunque causa) - Rilevazione continua durante l'intero studio per gli eventi avversi. |
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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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 6 |
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 | Yes |
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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 30 |
E.8.9.2 | In all countries concerned by the trial days | 0 |