| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with an established histological diagnosis of MCL on lymph‐node biopsy, bone marrow biopsy, or extranodal tissue. |
| Sono eleggibili pazienti con una diagnosi istologica di diagnosi di linfoma mantellare eseguita su linfonodo, BOM, o tessuto estranodale. |
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| E.1.1.1 | Medical condition in easily understood language |
| Mantle cell Lymphoma |
| Linfoma Mantellare |
|
| 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 | 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 |
|
| 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 |
| The primary objective is to determine the activity (complete remission rate according to Cheson 2007 criteria) and safety of age‐adjusted Rituximab‐Bendamustine‐Cytarabine (RBAC500) regimen at the end of treatment in older untreated patients with MCL. |
| L'obiettivo primario è quello di determinare l'attività (tasso di remissione completa secondo criteri Cheson 2007) e la sicurezza del regime Rituximab-bendamustina-citarabina (RBAC500) alla fine del trattamento nei pazienti anziani non trattati con MC |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objectives are to determine: ‐ The rate of molecular response (characterized by labs of the FIL) ‐The progression‐free survival (PFS) ‐The overall survival (OS) ‐The duration of responses (DOR) ‐The rate of patients that complete the expected treatment schedule (6 courses) ‐ The rate of patients that are subject to dose reductions or delays |
| Gli obiettivi secondari sono di determinare: - Il tasso di risposta molecolare - La sopravvivenza libera da progressione (PFS) -La sopravvivenza globale (OS) -La durata della risposta (DOR) -Il tasso di pazienti che completano lo schema di trattamento previsto (6 cicli) - Il tasso di pazienti che sono soggetti a riduzione della dose o ritardi |
|
| 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 |
OTHER SUBSTUDIES:
MDR Study: Molecular response is the proportion of patients with molecular rearrangements at baseline that become negative during treatment, measured by qualitative and quantitative PCR.
|
ALTRI SOTTOSTUDI:
Studio sulla Malattia minima residua e sulla risposta molecolare come pervisto dagli end point
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| E.3 | Principal inclusion criteria |
| • Previously untreated patients with MCL aged >65 years if they are FIT according to the geriatric CGA assessment. • age 60‐65 years not eliglible to high‐dose chemotherapy plus transplantation, FIT or UNFIT according to the geriatric CGA assessment. • ECOG performance status ≤2. • Positivity for cyclin D1 and SOX11 [the latter being mandatory in cases lacking cyclin D1‐ or t(11;14)‐negative], CD20 and CD5. • Adequate renal function (Creatinine clearance >40 mL/min), with preserved diuresis. • Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <2.5 x upper limit of normal (ULN) value, total bilirubin <2 mg/dL, unless directly attributable to the patient’s tumor. • Hepatitis B core antibody (HBcAb) positive/HBsAg negative/HBV‐DNA negative patients may be enrolled if correct antiviral prophylaxis is administered at least 2 weeks before initiating protocol treatment. • Written informed consent. |
| • pazienti con MCL precedentemente non trattati di età > 65 anni se sono FIT in base alla valutazione geriatrica CGA. • età 60-65 anni non eliglible a chemioterapia ad alte dosi più trapianto, FIT o non idonee in base alla valutazione geriatrica CGA. • performance status ECOG ≤ 2. • positività per la ciclina D1 e SOX11 [quest'ultimo è obbligatorio nei casi mancano ciclina D1-o t (11; 14)-negativi], CD20 e CD5. • Adeguata funzionalità renale (clearance della creatinina > 40 ml / min), con diuresi conservata. • Adeguata funzionalità del fegato: alanina aminotransferasi (ALT) / aspartato aminotransferasi (AST) <2.5 volte il limite superiore del valore normale (ULN), bilirubina totale <2 mg / dl, a meno che tali valori non siano direttamente imputabili al tumore del paziente. • anticorpi anti core dell'epatite B (HBcAb) positivi / HBsAg negativi / pazienti HBV-DNA negativi possono essere arruolati se effettuata una corretta profilassi antivirale almeno 2 settimane prima di iniziare il protocollo di trattamento. • consenso informato scritto. |
|
| E.4 | Principal exclusion criteria |
| • Human immunodeficiency virus (HIV) positive. • Previous treatment for lymphoma • Medical conditions or organ injuries that could interfere with administration of therapy. • Active bacterial, viral, or fungal infection requiring systemic therapy. • Seizure disorders requiring anticonvulsant therapy. • Severe chronic obstructive pulmonary disease with hypoxiemia. • History of severe cardiac disease: New York Heart Association (NYHA) functional class III‐IV, myocardial infarction within 6 months, ventricular tachyarrhythmias, dilatative cardiomyopathy, or unstable angina. • Uncontrolled diabetes mellitus. • Active secondary malignancy. • Known hypersensitivity or anaphylactic reactions to murine antibodies and proteins, to Bendamustine ormannitol. • Major surgery within 4 weeks of study Day 1. • HBsAg+ • HCVAb+ patients with active viral replication (HCV‐RNA+ with AST>2 x normal limit) • Any co‐existing medical or psychological condition that would preclude participation in the study or compromise the patient’s ability to give informed consent, or that may affect the interpretation of the results, or render the patient at high risk from treatment complications. • CNS involvement (a diagnostic lumbar puncture will be performed in patients with the blastoid variant of MCL) |
| • HIV positivo • precedente trattamento per il linfoma • Condizioni mediche o lesioni d'organo che potrebbero interferire con la somministrazione della terapia. • Attiva infezione batterica, virale, fungina o che richiede terapia sistemica. • Disturbi del sequestro che richiede terapia anticonvulsiva. • Grave malattia polmonare ostruttiva cronica con hypoxiemia. • Storia di una grave malattia cardiaca: la New York Heart Association (NYHA) di classe funzionale III-IV, infarto miocardico entro 6 mesi, tachiaritmie ventricolari, cardiomiopatia dilatativa, o angina instabile. • diabete mellito non controllato. • tumore maligno secondario. • note reazioni di ipersensibilità o anafilattiche agli anticorpi murini e proteine, per bendamustina o mannitolo. • chirurgia maggiore entro 4 settimane dalla giornata di studio 1. • HBsAg + • HCVAb + pazienti con attiva replicazione virale (HCV-RNA + con AST> 2 volte il limite normale) • Eventuale co-esistente condizione medica o psicologica che potrebbe precludere la partecipazione allo studio o compromettere la capacità del paziente di dare un consenso informato, o che possono influenzare l'interpretazione dei risultati, o rendere il paziente ad alto rischio di complicazioni per il trattamento. • coinvolgimento del SNC (una puntura lombare diagnostica sarà eseguita in pazienti con la variante blastoid di MCL) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Primary efficacy end point of the study is the proportion of CR defined according to Cheson criteria (2007) at the end of treatment (6 or 4 cycles). Primary safety end point is the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity. |
| L'Endpoint primario di efficacia dello studio è la percentuale di Risposte Complete definita secondo criteri di Cheson (2007) alla fine del trattamento (6 o 4 cicli). L'End point primario di sicurezza è la presenza di uno dei criteri definiti per l'interruzione dello studio o di qualsiasi episodio di tossicità rilevante. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| Secondary end points are MRD defined response, OS, PFS and DOR (Cheson 2007). Molecular response is the proportion of patients with molecular rearrangements at baseline that become negative during treatment, measured by qualitative and quantitative PCR. |
| Gli end point secondari sono la risposta definita secondo MRD, OS, PFS e DOR (Cheson 2007). La risposta molecolare è la proporzione di pazienti con riarrangiamenti molecolari al basale, che diventano negativi durante il trattamento, misurata con PCR qualitativa e quantitativa. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| OS is measured from enrollment until death from any cause. PFS is measured from the time of enrollment until disease progression, relapse or death from any cause. DOR is measured from the first assessment that documents response (CR or PR) to the date of disease relapse or progression. |
| L'OS è il periodo di tempo che va dall'arruolamento al decesso per ogni causa; PFS è misurato dal momento dell'arruolamento fino alla progressione della malattia, recidiva o morte per qualsiasi causa. DOR è misurata dal momento di valutazione della prima risposta (CR o PR) alla data di recidiva o di progressione della malattia. |
|
| 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 | 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 | 56 |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 24 |
| E.8.9.1 | In the Member State concerned days | 0 |
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