E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse large B-cell lymphoma DLBCL |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012821 |
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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 is to compare maintenance therapy with enzastaurin versus placebo, in terms of the overall disease-free survival DFS time in patients with DLBCL in first remission with high risk of relapse initial IPI score 3 following R-CHOP using a 14- or 21-day cycle. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to compare the following time-to-event efficacy variables between treatment arms rate of DFS at 2 years DFS2 event-free survival EFS rate of EFS at 2 years EFS2 OS time to compare adverse events between treatment arms to compare health-related quality of life using the FACT-Lym Cella et al. 2005 to assess health status using the EQ-5D scale EuroQol Group 1990 to assess biomarkers relevant to enzastaurin and disease state and their correlation to clinical outcome to characterize the pharmacokinetics PK of enzastaurin and its metabolites using a sparse sampling strategy. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients may be included in the study only if they meet all of the following criteria 1 have had a histologically confirmed diagnosis of DLBCL by the World Health Organization classification Harris et al. 1999 at the time of original diagnosis. Pathology must be reviewed and confirmed prior to enrollment at the investigational site where the patient is entered. Patients may be entered and randomized based on local pathology; however, an independent centralized pathology review will be performed on all enrolled patients see Section 6.4.1 . Patients with a prior history of an indolent lymphoma or a histological diagnosis of follicular Grade 3 lymphoma will not be eligible for enrollment. 2 if any gallium scan was performed, the most recent gallium scan must be negative. However, gallium scans are not a required study procedure. 3 if any PET scan was performed, the most recent PET scan must be negative. However, PET scans are not a required study procedure. 4 have completed six or eight 21-day cycles of R-CHOP, or six 14-day cycles of R-CHOP as first-line therapy for DLBCL. Refer to Section 5.5 for recommended regimens. The patient must have achieved a CR or CRu and have not subsequently progressed according to International Workshop criteria Cheson et al. 1999 . 5 have an IPI score 3 at time of original diagnosis refer to Protocol Attachment JCBJ.4 . 6 have had Stage 3 or 4 disease, or have had Stage 2 with bulky disease defined as 10 cm , at time of original diagnosis. 7 have given informed consent. 8 have an estimated life expectancy of at least 12 weeks. 9 have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group ECOG scale see Protocol Attachment JCBJ.7; Oken et al. 1982 . 10 exhibit patient compliance and geographic proximity that allow for adequate follow-up. 11 have adequate organ function as follows Hepatic total bilirubin 1.5 times upper limit of normal ULN ; alanine transaminase ALT and aspartate transaminase AST 2.5 times ULN Renal serum creatinine 1.5 times ULN Adequate bone marrow reserve platelets 50 x 109/L, absolute neutrophil count ANC 1.0 x 109/L, hemoglobin 8 g/dL. 12 male and female patients with reproductive potential must use an approved contraceptive method, if appropriate for example, intrauterine device IUD , birth control pills, or barrier device during and for 3 months after discontinuation of study treatment. Women with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment. 13 are at least 18 years of age. 14 Patient must receive on-study therapy no later than 42 days from their last cycle Day 1 of induction therapy. |
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria 1 have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. 2 receive concurrent administration of any other systemic anticancer therapy. 3 have received radiation therapy to more than one targeted lesion local residual disease for treatment of lymphoma. 4 are pregnant or breastfeeding. 5 have central nervous system CNS metastases unless the patient has completed successful local therapy for CNS metastases and has been off of corticosteroids for at least 4 weeks before starting study therapy . In the absence of a clinical suspicion of brain metastases, no screening computed tomography CT or magnetic resonance imaging MRI scan before enrollment is required. 6 have serious concomitant disorder, including active bacterial, fungal, or viral infection, incompatible with the study at the discretion of the investigator . 7 have human immunodeficiency virus HIV associated lymphomas. 8 have a second primary malignancy except adequately treated basal cell carcinoma of the skin . Patients who had another malignancy in the past, but have been disease-free for more than 5 years, are eligible. 9 have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV see Protocol Attachment JCBJ.5 . 10 are unable to swallow tablets. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint for this trial is overall DFS. Overall DFS time is defined as the time from the date of study enrollment to the first date of objectively determined disease recurrence 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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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.8.3 |
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 |
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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
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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 |