E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029547 |
E.1.2 | Term | Non-Hodgkin's lymphoma |
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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 |
The primary objective for this study is as follows: • To evaluate clinical benefit in terms of PFS, as assessed by an IRF, for GA101 when used in combination with bendamustine compared with bendamustine alone in patients with indolent NHL refractory to prior rituximab-containing therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives for this study are as follows: • To compare OS between study arms • To evaluate in each study arm and compare between study arms the following: overall response rate (ORR = rate of complete response [CR] + partial response [PR]) and CRR after the end of 6 months of treatment; best ORR achieved during treatment or within 12 months of the start of treatment; disease-free survival in CR patients; and duration of response in patients with CR and PR • To compare event-free survival (EFS) between the two study arms • To evaluate and compare the safety profiles of patients treated with the combination of GA101 + bendamustine and bendamustine alone. • To characterize the pharmacokinetics of GA101 in combination with bendamustine and evaluate for drug-drug interactions by comparing the pharmacokinetics of the combination with the pharmacokinetics of bendamustine alone Et al. |
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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 |
FARMACOGENETICA: Versione:12-2009 Data:2009/12/18 Titolo:DNA REPOSITORY SUBSTUDY IN ASSOCIATION WITH RO5072759 (GA101) STUDY GAO4753g, dated 18 december 2009 Obiettivi:The primary objective of this study is to perform exploratory analyses to generate hypotheses identifying genes associated with treatment response, toxicity, or disease risk. If such genetic hypotheses are identified, they may be tested in future clinical studies within this therapeutic area.
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E.3 | Principal inclusion criteria |
Patients must meet the following inclusion criteria to be eligible for study entry: • History of histologically documented, CD20+, indolent NHL (including follicular lymphoma, grades 1-3a; marginal zone lymphoma [including splenic, nodal, and extra-nodal]; and small lymphocytic lymphoma with an absolute lymphocyte count < 5000). For each patient, a prior biopsy demonstrating CD20 positivity of tumor cells must be available locally at the investigator site prior to dosing; this will be further confirmed retrospectively following central pathology review. A lymph node biopsy to rule out transformation is required in patients for whom there is clinical suspicion of transformation. • Refractory to a regimen containing rituximab, defined as no response to, or progression within 6 months of completion of, the last dose of rituximab therapy (either as monotherapy or in combination with chemotherapy), including: Patients with progressive disease while receiving rituximab monotherapy, rituximab + chemotherapy, or rituximab maintenance therapy, after having received at least one full dose (375 mg/m2) of rituximab Patients with no clinical response (PR or better) to a rituximab-containing regimen consisting of at least 4 weekly doses of rituximab monotherapy or at least 4 cycles of rituximab + chemotherapy Patients with disease relapse (after having achieved a clinical response) within 6 months of completion of the last dose of rituximab therapy in a regimen consisting of at least 4 weekly doses of rituximab monotherapy or at least 4 cycles of rituximab + chemotherapy • Previously treated with a maximum of three unique chemotherapy containing treatment regimens (“unique treatment regimen” is defined as at least two cycles of treatment of a planned multi-dose regimen containing chemotherapy with or without antibody-based therapy). Prior autologous stem cell transplant or radioimmunotherapy is permitted if it is completed more than 6 months prior to study entry. • All patients must have at least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan). Tumor response will be based on the status of all areas of disease and assessed according to the modified response criteria for NHL (Cheson et al. 2007; see Appendix E). • Able and willing to provide written informed consent and to comply with the study protocol. • Age >= 18 years. • ECOG performance status of 0, 1, or 2 (see Appendix D). |
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E.4 | Principal exclusion criteria |
The following will exclude patients from study entry: • Prior use of any monoclonal antibody (other than anti-CD20) within 3 months of the start of Cycle 1 • Chemotherapy or other investigational therapy within 28 days prior to the start of Cycle 1 • Prior treatment with bendamustine within 1 year of the start of Cycle 1 Patients with prior bendamustine treatment (i.e., greater than 1 year prior to the start of Cycle 1) must have achieved either a partial or complete response to the bendamustine regimen of at least 6 months in duration prior to relapse/progression in order to be eligible • Prior allogeneic stem cell transplant • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (e.g., patients in whom re-dosing with rituximab would be contraindicated for safety reasons) • History of sensitivity to mannitol • Central nervous system lymphoma or histological evidence of transformation to high grade or diffuse large B-cell lymphoma • History of other malignancy that could affect compliance with the protocol or interpretation of results Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will also be excluded, unless the malignancy has been in remission without treatment for >= 2 years prior to enrollment. • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm) • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks of the start of Cycle 1 • Vaccination with a live vaccine a minimum of 28 days prior to randomization • Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis • Any of the following abnormal laboratory values: Creatinine > 1.5 times the upper limit of normal (unless creatinine clearance normal), or creatinine clearance < 40 mL/min Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the upper limit of normal Total bilirubin ≥3 x ULN Platelet count < 75 x 10^9/L (unless due to underlying disease, as established by extensive bone marrow involvement) For patients with autologous prior stem cell transplant, platelet count < 100 x 10^9/L (unless due to underlying disease as established by extensive bone marrow involvement). Neutrophil count < 1.5 x 10^9/L (unless due to underlying disease, as established by extensive bone marrow involvement) Hemoglobin <10g/dL (unless due to underlying disease, as established by extensive bone marrow involvement) Et al. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival is defined as the time from randomization to the first occurrence of progression or relapse as assessed by the IRF, or death from any cause. |
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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 | Yes |
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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | 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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 145 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | Yes |
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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Lo studio si concluder� quando si verificheranno 264 decessi, approssimativamente 4 anni dopo l`arruolamento dell`ultimo paziente. Lo Sponsor ha il diritto di interrompere lo studio in ogni momento. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |