E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
relapsed non follicular non-Hodgkin s Lymphoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10029621 |
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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 demonstrate a statistical benefit in overall response rate ORR of the Bortezomid/Rituximab association in relapsed /refractory indolent non-follicular and mantle cell non-Hodgkin lymphoma patients that was na ve or sensitive to rituximab |
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E.2.2 | Secondary objectives of the trial |
1 To evaluate the Complete Response CR rate of relapsed /refractory indolent non-follicular and mantle cell non-Hodgkin lymphoma patients treated with the Bortezomid/Rituximab association 2 To evaluate the efficacy of the Bortezomid/Rituximab association to prolong 2-year failure-free survival FFS rate compared to historical standard treatment 3 To assess the safety of Bortezomid/Rituximab association in relapsed/refractory indolent non follicular and mantle cell non Hodgkin lymphoma patients 4 To evaluate overall survival of the patients treated with Bortezomid/Rituximab association |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Patients with na ve or sensitive rituximab indolent non-follicular and mantle cell non-Hodgkin s Lymphoma disease that had failed to respond or relapsed after primary therapy. There is a demonstrated progressive disease requiring further treatment. Histological subtype included into the study are are as follows Attachment 2 WHO classification of Lymphoma 61623; Small lymphocytic/lymphoplasmocytic lymphoma; 61623; Nodal marginal zone Lymphoma MALT lymphoma are excluded 61623; Splenic marginal zone lymphoma 61623; Mantle cell lymphoma A lympnode biopsy is advisable if it is not harmful for the patients, before enrollement of the patient into the study in order to confirm diagnosis and to rule out histologic transformation. Lymphnode biopsy should be performed within 6 months before study entry. 2. Age 18-75 3. Relapse or failure to respond after one or more maximum three lines of chemotherapy 4. Any type of prior chemotherapy, rituximab included. Patients who had received high dose chemotherapy and ASCT can be enrolled into the study 5. Na ve or sensitive rituximab disease. If the patient received Rituximab, he/she must have responded and the TTP from the last dose to rituximab must have been 6 months or more. 6. Measurable and/or evaluable disease. 7. Adequate haematological counts ANC 1.0 x 109/L and PLTs counts 75 x 109/L unless due to bone marrow involvement by lymphoma. 8. Conjugated bilirubin up to 2 x ULN. 9. Alkaline phosphatase and transaminases up to 2 x ULN. 10. Creatinine clearances 8805;30 m/min. 11. Non peripheral neuropathy or CNS disease. 12. Life expectancy 6 months. 13. Performance status 2 according to ECOG scale. 14. Written informed Consent |
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E.4 | Principal exclusion criteria |
Potential patients who meet any of the following criteria will be excluded from participating in the study 1. Has known or suspected hypersensitivity or intolerance to rituximab, boron, mannitol, or heparin, if an indwelling catheter is used 2. History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances 3. Uncontrolled diabetes if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug 4. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association NYHA Class III or IV heart failure Attachment 5, NYHA Classification of Cardiac Disease , uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis 5. History of hypotension or has decreased blood pressure sitting systolic blood pressure SBP 100 mmHg and/or sitting diastolic blood pressure DBP 60 mmHg 6. Pregnant or breastfeeding 7. Neuropathy Grade 2 8. HIV positivity 9. HBV positivity with the exception of patients with HBVcAb , HbsAg -, HBs Ab /- with HBV-DNA negative 10. HCV positivity with the exception of patients with no signs of active chronic hepatitis histologically confirmed 11. Active opportunistic infection 12. Receipt of extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 4 weeks before enrollment 13. Exposure to rituximab within 24 weeks before screening 14. Have received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study. 15. Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response Rate ORR Complete Remission, Complete Remission Unconfirmed, Partial Remission. |
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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 | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
E.8.2.3.1 | Comparator description |
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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.8.5 | 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 | Information not present in EudraCT |
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
| |
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 | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |