E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously untreated, activated B-cell (ABC) type diffuse large B-cell lymphoma (DLBCL). |
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E.1.1.1 | Medical condition in easily understood language |
DLBCL is a blood cell cancer of B-lymphocytes which are part of the immune system. There are different types of DLBCL and this study is for patients with DLBCL of the ABC type who haven't been treated |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012859 |
E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) stage II |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012855 |
E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012860 |
E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) stage III |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012861 |
E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) stage IV |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of lenalidomide, rituximab, cyclophosphamide, doxorubicin,vincristine, and prednisone (R2-CHOP) chemotherapy versus placebo, rituximab,cyclophosphamide, doxorubicin, vincristine, and prednisone (placebo-R-CHOP) chemotherapy in subjects who have previously untreated ABC type DLBCL. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to compare the safety of lenalidomide, rituximab, cyclophosphamide, doxorubicin,vincristine, and prednisone (R2-CHOP) chemotherapy versus placebo, rituximab,cyclophosphamide, doxorubicin, vincristine, and prednisone (placebo-R-CHOP) chemotherapy in subjects who have previously untreated ABC type DLBCL |
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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 |
The pharmacokinetic (PK) substudy is designed to evaluate the PK of lenalidomide when co-administered with and without R-CHOP. It will be conducted at selected sites and will be optional for subjects at those sites. Approximately 20 subjects will be included in the PK substudy. |
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E.3 | Principal inclusion criteria |
-Histologically proven Diffuse Large B-Cell Lymphoma (DLBCL) of the ABC type.
-Newly diagnosed, previously untreated Diffuse Large B-Cell Lymphoma (DLBCL)
-Measurable Diffuse Large B-Cell Lymphoma (DLBCL) disease by Computed Tomography (CT)
-Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
Age from 18. For subjects > 80years, if their ECOG ≤ 1; each of their
individual organ systems scores is ≤ 2 using the Modified Cumulative
Illness Rating Scale (CIRS) for co-morbidity; and if they would otherwise
be eligible for full-dose R-CHOP per local practice.
- HCV patients who do not have hepatitis C and who are acceptable for
R-CHOP chemotherapy.
- Hemoglobin criterion 11c≥7.5 g/dL |
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E.4 | Principal exclusion criteria |
-Diagnosis of lymphoma histologies other than Diffuse Large B-Cell Lymphoma (DLBCL).
-History of malignancies, other than Diffuse Large B-Cell Lymphoma (DLBCL), unless the patient has been disease free for 5 years or more.
-Known seropositive for, or history of, active Human Immunodeficiency Virus (HIV) (testing is at investigator discretion)
-Seropositive for HBV (testing is required)
-Seropositive for HCV, with chronic hepatisc C, or subjects with an active hepatitis infection (testing is required)
-Contraindication to any drug in the chemotherapy regimen, and specifically: LVEF < 45% or peripheral neuropathy grade > =2
- T-cell/histiocyte rich Diffuse Large B-Cell Lymphoma (DLBCL) cases
-Post-transplant Lymphoproliferative Disorder (PTLPD) cases |
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E.5 End points |
E.5.1 | Primary end point(s) |
-Progression-free Survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-This will be analyzed after a total of 192 PFS events in the ITT population have been observed. This is estimated to occur approximately 42 months after the first subject is randomized.
-An interim analysis for futility is planned after a total of 96 PFS events in the ITT population have been observed. This is estimated to occur approximately 28 months after the first subject is randomized. |
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E.5.2 | Secondary end point(s) |
Key secondary endpoint
-Event-free Survival (EFS)
Other secondary endpoints
-Overall Survival (OS)
-Complete Response (CR) rate
-Duration of CR
-Time to next lymphoma therapy (TTNLT)
-Objective response rate (ORR)
-Health-related quality of life (HRQoL) as measured by the EuroQuol 5 Dimension Scale (EQ-5D) and the Functional Assessment of Cancer Therapy for Patients with Lymphoma (FACT Lym) standardized measures of health status. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- At time of primary endpoint evaluation (applies for all secondary end points listed above) |
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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 | 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 | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
exploratory objectives ie
- to compare the progression free survival 2 and genetic mutations
- to explore minimal residual disease
- to explore molecular markers
- to explore PK parameters of lenalidomide |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 147 |
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 | No |
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 |
Australia |
Belgium |
Canada |
China |
Czech Republic |
France |
Ireland |
Italy |
Japan |
Korea, Republic of |
Netherlands |
New Zealand |
Poland |
Portugal |
Russian Federation |
Spain |
Switzerland |
Taiwan |
Turkey |
United States |
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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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The date of the last visit of the last subject to complete the study, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the Statistical Analysis Plan, whichever is the later date |
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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 | 8 |
E.8.9.1 | In the Member State concerned months | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |