E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse large B-cell lymphoma |
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MedDRA Classification |
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 efficacy and safety of the Zevalin study regimen compared with observation alone in patients with DLBCL who are in complete remission (CR or CRu) after first-line CHOP-R. Overall survival (OS) will be the primary endpoint. |
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E.2.2 | Secondary objectives of the trial |
Disease-free survival (DFS) will be the secondary endpoint. An additional secondary endpoint will be health-related quality of life (HRQL) as assessed by the patient using standard questionnaires (FACT-G and EuroQoL EQ-5D). |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Histologically confirmed, Ann Arbor stage II, III, or IV DLBCL according to the REAL/WHO classification (from initial diagnosis made prior to starting CHOP-R therapy) 2. Central pathology review confirming the DLBCL diagnosis and CD20 positivity, and no evidence of DLBCL in bone marrow 3. First-line treatment of DLBCL must have been 6 or 8 cycles of standard CHOP chemotherapy (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 up to a maximum of 2 mg on day 1, and at least 40 mg/m2/day prednisone on Days 1 to 5 every three weeks) in combination with rituximab (375 mg/m2) 4. Complete remission (CR) or unconfirmed complete remission (CRu) according to the International Workshop Response Criteria for NHL described by Cheson et al and modified for this study after first-line treatment with CHOP-R. CT scans of the neck, thorax, abdomen, and pelvis must have been performed within 6 weeks after the last dose of the last course of CHOP R 5. Central radiographic review of the CT scans (neck, thorax, abdomen, and pelvis) from before and after first-line treatment with CHOP-R fulfilling the radiological requirements for CR/CRu 6. Patients 60-years-of-age or older at time of randomization 7. WHO performance status (PS) of 0 to 2 within 1 week of randomization 8. Absolute neutrophil count (ANC) >= 1.5 x 109/L within 1 week of randomization 9. Hemoglobin (Hgb) >= 10 g/dL within 1 week of randomization 10. Platelets >= 150 x 109/L within 1 week of randomization 11. Life expectancy of 3 months or longer 12. Written informed consent obtained according to local guidelines |
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E.4 | Principal exclusion criteria |
1. Presence of any other malignancy or history of prior malignancy except non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma 2. Prior radioimmunotherapy, radiation therapy, or any other NHL therapy except first-line CHOP-R 3. Presence of gastric, central nervous system (CNS), or testicular lymphoma at first diagnosis 4. Histological transformation of low-grade NHL 5. Known seropositivity for hepatitis C virus (HCV) or hepatitis B surface antigen (HbsAg) 6. Known history of HIV infection 7. Abnormal liver function: total bilirubin > 1.5 x ULN or ALT > 2.5 x ULN within 1 week of randomization 8. Abnormal renal function: serum creatinine > 2.0 x ULN within 1 week of randomization 9. Nonrecovery from the toxic effects of CHOP-R therapy 10. Known hypersensitivity to murine or chimeric antibodies or proteins 11. G-CSF or GM-CSF therapy within two weeks (or four weeks if pegylated) prior to screening laboratory sampling 12. Concurrent severe and/or uncontrolled medical disease (e.g., uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months of study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study 13. Male and female patients of child-bearing potential unwilling to practice effective contraception during the study and unwilling or unable to continue contraception for 12 months after their last dose of study treatment 14. Female patients who are pregnant or are currently breastfeeding 15. Treatment with investigational drugs less than 4 weeks before the planned Day 1 or nonrecovery from the toxic effects of such therapy 16. Surgery less than 4 weeks before the planned Day 1 or nonrecovery from the side effects of such surgery 17. Concurrent corticosteroid use for any reason except as premedication in case of known or suspected allergies to contrast media or as premedication for potential side effects of rituximab treatment 18. Unwillingness or inability to comply with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Observation only (no treatment) |
|
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 | Yes |
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 | 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
|
IDMC to review safety & efficacy, to recommend continuation/stop of study based on group-sequential design:success, futility, or insufficient data. Analyses after 20 events (deaths from any cause), then after every 10 cases up to maximum 76. Once IDMC recommendation is accepted by steering committee, recruitment to be stopped. All treated patients to be followed until last patient completed 12 weeks safety period. IDMC Charter to be established prior to enrolling the first patient in the study. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |