E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with advanced untreated Indolent non Follicular non-Hodgkin Lymphomas |
Pazienti con Linfoma non Hodgkin Indolente non Follicolare non precedentemente trattati. |
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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 | 10065856 |
E.1.2 | Term | Non-Hodgkin's lymphoma unspecified histology indolent |
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 overall response rate (CR+PR) obtained with Bendamustine in combination with Rituximab in previously untreated INFL. |
Valutare il tasso di risposta globale (RC+RP) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety of Bendamustine in combination with Rituximab in previous untreated INFL • To evaluate the overall survival (OS) • To evaluate the progression-free survival (PFS) • To evaluate the disease –free survival (DFS) |
• Valutare il profilo di tossicita' • Valutare la sopravvivenza globale (OS) • Valutare la sopravvivenza libera da progressione (PFS) • Valutare la sopravvivenza libera da malattia (DFS) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Understand and voluntarily sign an informed consent form 2) Histological (bone marrow or lymph nodes biopsy) proven diagnosis of B-cell CD20- positive non-follicular NHL according to REAL/WHO Classification: i. small lymphocytic lymphoma-SLL (bone marrow or lymph nodes biopsy) ii. lymphoplasmacytic/citoid lymphoma/ Waldenstrom macroglobulinemia (bone marrow or lymph nodes biopsy) iii. nodal marginal zone lymphoma (lymph nodes biopsy) 3) Untreated patients 4) Stage III or IV or stage II with more than three involved sites 5) Presence of at least one of the following criteria for the definition of active disease a. Systemic symptoms b. Hemoglobin less than 10 g/dL (due to lymphoma) c. Platelets less than 100 x 109/L (due to lymphoma) d. Diffuse bone marrow infiltrate e. Lymphocyte doubling time less than 12 months (in leukemic cases) f. Bulky disease (>7 cm) 6) Aged 18 - 75 Life expectancy >6 months 7) ECOG performance status 0-2 8) LVEF ≥45% or FS ≥37% 9) ANC ≥1 x 109/l and Platelets count ≥75 x 109/l, unless due to bone marrow involvement by follicular lymphoma 10) Creatinine up to 1.5 x ULN 11) Conjugated bilirubin up to 2 x ULN 12) Alkaline phosphatase and transaminases up to 2 x ULN 13) Written informed content |
1) Comprensione e firma volontaria del consenso informato 2) Esame istologico (midollo osseso o biopsia linfonodale) comprovante la diagnosi di linfoma NHL indolente non follicolare B-cell CD20 positivo sulla base della classificazione REAL/WHO: i. linfoma a piccole cellule – SLL (biopsia del midollo osseo o dei linfonodi) ii. lymphoplasmacytic/citoid lymphoma/ Waldenstrom macroglobulinemia (biopsia del midollo osseo o dei linfonodi) iii. linfoma della zona marginale nodale (bipsia dei linfonodi) 3) Pazienti non trattati 4) Stadio III o IV o stadio II con piu' di tre siti coinvolti 5) Presenza di almeno uno dei seguenti criteri per la definizione di malattia attiva: a. Sintomi sistemici b. Emoglobina inferiore a 10 g/dL (a causa del linfoma) c. Piastrine inferiori a 100 x 109/L (a causa del linfoma) d. Midollo osseo infiltrato diffuso e. Tempo di raddoppiamento dei linfociti inferiore a 12 mesi (in casi leucemici) f. Malattia bulky (>7 cm) 6) Eta' compresa tra 18 e 75 anni Aspettativa di vita > 6 mesi 7) ECOG performance status 0-2 8) LVEF ≥45% o FS ≥37% 9) ANC ≥1 x 109/l e conta piastrinica ≥75 x 109/l, tranne in caso di coinvolgimento del midollo osseo da linfoma follicolare 10) Creatinina fino a 1.5 x ULN 11) Bilirubina coniugata fino a 2 x ULN 12) Fosfatasi alcalina e transaminasi fino a 2 x ULN 13) Consenso informato scritto |
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E.4 | Principal exclusion criteria |
1. Patients with diagnosis of marginal zone lymphoma of splenic or MALT origin 2. Patients with diagnosis of typical Chronic Lymphocytic Leukemia (CLL) 3. Men not agreeing to take adequate contraceptive precautions during and for at least 6 months after cessation of therapy 4. History of other malignancies within 3 years prior to study entry except for: adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage, localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent 5. Medical condition requiring long term use (>1 months) of systemic corticosteroids 6. Active bacterial, viral, or fungal infection requiring systemic therapy 7. Concurrent medical condition which might exclude administration of therapy 8. Cardiac insufficiency (NYHA grade III/IV) 9. Myocardial infarction within 6 months of entry on study 10. Severe chronic obstructive pulmonary disease with hypoxemia 11. Severe diabetes mellitus difficult to control with adequate insulin therapy 12. Hypertension that is difficult to control 13. Impaired renal function with creatinine clearance <30 ml/min 14. HIV positivity 15. HBV positivity with the exception of patients HbsAg negative and Ab anti-Hbcore positive (these patientes need to receive prophylaxis with Lamivudine) 16. HCV positivity with the exception of patients with HCV RNA negative. 17. CNS involvement by lymphoma 18. Participation at the same time in another study in with investiogational drugs are used 19. Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins 20. Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent 21. Women in pregnancy or breastfeeding |
1. Pazienti con diagnosi di linfoma della zona marginale di origine splenica o MALT 2. Pazienti con diagnosi di leucemia linfocitica cronica tipica (LLC) 3. Uomini che non accettano di adottare adeguate misure contraccettive durante la terapia e per almeno 6 mesi dopo la sospensione della terapia 4. Storia di altri tumori maligni nei 3 anni precedenti all'entrata nello studio ad eccezione di: carcinoma trattato adeguatamente in situ della cervice uterina, del cancro della pelle basale o cellule squamose, di basso grado, stadio precoce, il cancro alla prostata localizzato trattati chirurgicamente con intento curativo; carcinoma duttale in situ buona prognosi del mammella trattati con lumpectomy sola con intento curativo 5. Patologie che richiedono l'uso a lungo termine (> 1 mese) di corticosteroidi per via sistemica 6. Infezioni batteriche, virali o fungine attive che necessitano di terapia sistemica 7. Concomitante condizione medica che possa escludere la somministrazione della terapia 8. Insufficienza Cardiaca (NYHA grado III/IV) 9. Infarto miocardico nei 6 mesi precedenti all'entrata nello studio 10. Grave malattia polmonare ostruttiva cronica con ipossiemia 11. Diabete mellito grave di difficile controllo con la terapia insulinica adeguata 12. Ipertensione difficile da controllare 13. Compromissione della funzione renale con clearance della creatinina <30 ml / min 14. HIV positivita' 15. HBV positivita' con l'eccezione dei pazienti HBsAg negativi e anti-Ab Hbcore positiva (questi pazienti necessitano di ricevere la profilassi con lamivudina) 16. HCV positivita' con l'eccezione dei pazienti con HCV RNA negativo.. 17. Coinvolgimento del SNC da parte del linfoma 18. Partecipazione concomitante a un altro studio in cui vengono utilizzati farmaci sperimentali 19. Nota ipersensibilita' o reazioni anafilattiche a anticorpi murini o proteine 20. Eventuali altre coesistenti condizioni fisiche o psicologiche che precludano la partecipazione del paziente allo studio o che ne compromettano la capacita' di fornire un consenso informato 21. Donne in gravidanza o allattamento |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate and complete remission rate |
Tasso di risposta globale e tasso di remissione completa |
|
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 | 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 | No |
E.8.1.6 | Cross over | No |
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 | 29 |
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
|
La sperimentazione si concludera' dopo l'ultima visita di follow up dell'ultimo paziente arruolato nello studio. |
|
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 | 0 |