E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prognosis of high-risk patients with diffuse large B-cell lymphoma is still less then optimal. According to revised Int. Prognostic Index, patients with 3-5 adverse prognostic factors have only about 50% chance of survival in 4 years. In theory, there are 3 possibilities how to improve prognosis of patients with poor-risk DLBCL: intensification of induction therapy, high-dose consolidation treatment with autologous stem cell transplant or combination of both methods. |
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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 compare PFS in arms treated with intensive immuno-chemotherapy followed by observation or by HDT and ASCT in early PET negative (PET-) pts and To determine safety and PFS of intensified salvage immuno-chemotherapy followed by HDT and ASCT in early PET positive (PET+) pts. |
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E.2.2 | Secondary objectives of the trial |
To compare EFS and OS in arms treated with intensified immuno-chemotherapy followed by observation or by HDT and ASCT in early PET negative pts To determine ORR, CR, EFS and OS of the intensified salvage immuno-chemotherapy followed by HDT and ASCT in early PET positive pts and compare PFS, EFS and OS with outcomes of the early PET negative patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 18-60 years • Newly diagnosed, CD20 positive, untreated diffuse large B-cell lymphoma or composite follicular/diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma (according to the WHO classification) • High intermediate or high risk according to age adjusted International Prognostic Index (aaIPI 2-3) • No significant organ dysfunction, no active uncontrolled disease • ECOG Performance Status 0-3 • Ejection fraction of at least 50% as determined by echocardiography or alternative suitable method • Signed informed consent |
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E.4 | Principal exclusion criteria |
• Relapse of the lymphoma • CD20 negative diffuse large-cell lymphoma. • Post-transplant or other EBV-associated lymphoproliferative diseases. • Contraindication to any of planned treatments (for specific details refer to Summary of Product Characteristic (SPC) of each respective compound, including known hypersensitivity or allergy to murine products • Frank CNS involvement, diagnosed clinically, or by CT, NMR, or by unequivocal liquor positivity • Any history of malignant disease treated with chemotherapy or radiotherapy, with the exception of targeted radiotherapy for skin squamo-cellular carcinoma or basalioma. • Other serious disease or condition • HIV positivity, active hepatitis B or hepatitis C • Treatment within a clinical trial within 30 days prior to trial entry • Women who are breast-feeding, are not using effective contraception, are pregnant or do not agree not to become pregnant during the treatment phase and the 12 months thereafter. Men who do not agree not to father a child during the treatment phase and the 12 months thereafter. |
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E.5 End points |
E.5.1 | Primary end point(s) |
PET negative part of the protocol: To compare progression free survival (PFS) between arms treated with rituximab-based immunochemotherapy followed by observation or by HDT + ASCT in early PET negative young (under 60) high intermediate or high risk (aaIPI 2-3) CD20+ DLBCL patients. PET positive part of the protocol: To determine safety and progression free survival (PFS) of rituximab-based salvage immunochemotherapy followed by HDT + ASCT in early PET positive young (under 60) high intermediate or high risk (aaIPI 2-3) CD20+ DLBCL patients. |
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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 | No |
E.6.5 | Efficacy | No |
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) | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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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Criteria for subject withdrawal include (but are not limited to) death, toxicity, an intercurrent illness, noncompliance (including loss of subject to follow-up), voluntary withdrawal, and failure to meet the eligibility criteria. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 15 |