E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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 |
|
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 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 |
|
E.2.2 | Secondary objectives of the trial |
To compare OS between study arms • To evaluate in each study arm and compare between study arms the following: overall response rate 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 • To analyze pharmacoeconomics (medical resource utilization) in both arms of the study • To assess patient-reported outcomes (PROs) in both treatment arms |
|
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 |
DNA REPOSITORY SUBSTUDY IN ASSOCIATION WITH RO5072759 (GA101) STUDY GAO4753g, dated 18 december 2009 |
|
E.3 | Principal inclusion criteria |
- Histologically documented, CD20+, indolent NHL - 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). - Previously treated with a maximum of three unique chemotherapy‑containing treatment regimens -All patients must have at least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan).
|
|
E.4 | Principal exclusion criteria |
- 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 - 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 - Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results - 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 - Vaccination with a live vaccine a minimum of 28 days prior to randomization - Recent major surgery (within 4 weeks), other than for diagnosis - Presence of positive test results for Hepatitis B or Hepatitis C - Known history of HIV seropositive status - Positive test results for HTLV 1 virus in endemic countries - Women who are pregnant or lactating - Fertile men or women of childbearing potential unless 1) surgically sterile or 2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly -Ongoing corticosteroid use > 30 mg/day prednisone or equivalent |
|
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. |
|
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 |
|
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
|
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 | 19 |
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 |
|
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
|
The end of the study is defined as when 264 deaths have occurred, which will be approximately 4 years after the last patient is enrolled. The Sponsor has the right to terminate the study at any time. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 7 |
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 |