E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histological proved diagnosis of B-cell CD20-positive non follicular NHL according to REAL/WHO Classification: a. small lymphocytic lymphoma b. lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia, c. nodal marginal zone lymphoma d. splenic marginal zone lymphomae. e. extranodal non-gastric marginal zone lymphoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029463 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003911 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041652 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025345 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To evaluate the antitumor activity of oral lenalidomide 20mg/day (dd1-21q28) when given in combination with rituximab in patients with indolent non follicular NHL Relapsed after >2, but less than 4 prior lines of (immuno)chemotherapy.- Efficacy will be evaluated in term of ORR (CR+PR) and tumour control rate (CR+PR+SD) measured at 26 weeks, four weeks after the last (VI) Rituximab infusion. - To asses to the safety of R-lenalidomide evaluated by standard criteria (CTC-NCI 3.0). |
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E.2.2 | Secondary objectives of the trial |
- To compare the efficacy of lenalidomide in combination with rituximab in term of duration remission with those obtained after previous line of treatment, when rituximab was utilized.- To evaluate progression free survival (PFS), event free survival (EFS), duration of remission (DR).- To correlate clinical and biological markers of antilymphoma activity of lenalidomide/rituximab combination with specific transcriptional profiles of responder or non responder patients, by means of oligonucleotide microarray DNA analysis |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1)Histological proved diagnosis of B-cell CD20-positive non follicular NHL according to REAL/WHO Classification: a. small lymphocytic lymphoma b. lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia, c. nodal marginal zone lymphoma d. splenic marginal zone lymphomae e. extranodal non-gastric marginal zone lymphoma Tissue biopsy is mandatory when suspected pathological sites (nodal or extranodal) are easily accessible and in presence of extranodal non-gastric marginal or nodal marginal zone lymphoma diagnosis. In the other cases bone marrow biopsy, when representative, may be considered sufficient for defining lymphoma histotype. 2) Disease relapsing after >2, but less than 4 prior lines of (immuno)chemotherapy. At least one of previous treatment had to include rituximab 3) Presence of at least one of the following criteria for the definition of active disease: - systemic symptoms - bulky disease - progressive marrow failure and/or splenomegaly and/or lymph adenopathy 4) Age 18-75; 5) Life expectancy > 6 months; 6) ECOG performance status 0-2; 7) LVEF ³ 45%; 8) Creatinine clearance > 50 mL/min calculated by Cockcroft-Gault estimation; patients with creatinine clearance > 30 and < 50 mL/min, at physician discretion could enter in the study starting at lenalidomide dose level -2 (10 mg ); 9) Total bilirubin up to 2 x ULN. Total bilirubin values higher than 2 x ULN are admitted if related to localization of the disease; 10) Alkaline phosphatase up to 2 x ULN and transaminases up to 3 x ULN; 11) Female and male patients must agree to participate in pregnancy prevention program signed informed Consent 12) Written informed Consent. |
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E.4 | Principal exclusion criteria |
1) Previously untreated patients; 2) Patients with diagnosis of typical Chronic Lymphocytic Leukemia (CLL); 3) Women and men not agreeing to take adequate contraceptive precautions during and for at least 4 weeks after cessation of therapy; 4) Pregnant or lactating women; 5) History of other malignancies within 3 years prior to study entry except for adequately treated carcinoma in situ of the cervix or 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; 6) Active bacterial, viral or fungal infection requiring systemic therapy; 7) Concurrent co-morbid medical condition which might exclude administration of therapy; 8) Cardiac insufficiency (NYHA grade III/IV); 9)Myocardial infarction within 6 months of entry on the 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) Creatinine clearance < 30 mL/min calculated by Cockcroft-Gault estimation; 14)ANC < 1 x 109/L, unless due to lymphoma involvement and not responding to 5 days of G-CFS treatment. 15)Platelets count < 75.000/mm3 unless due to lymphoma involvement 16) HIV and HBV positivity |
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E.5 End points |
E.5.1 | Primary end point(s) |
- To evaluate the antitumor activity of oral lenalidomide 20mg/day (dd1-21q28) when given in combination with rituximab in patients with indolent non follicular NHL Relapsed after >2, but less than 4 prior lines of (immuno)chemotherapy.- Efficacy will be evaluated in term of ORR (CR+PR) and tumour control rate (CR+PR+SD) measured at 26 weeks, four weeks after the last (VI) Rituximab infusion. - To asses to the safety of R-lenalidomide evaluated by standard criteria (CTC-NCI 3.0). |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
studio di fase II, in aperto, multicentrico |
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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.8.3 |
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 | 15 |
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 | Information not present in EudraCT |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |