E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
high-risk diffuse large B-cell lymphoma (DLBCL ) |
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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 |
Main objective : evaluation of progression free survival on R-GEMOX and enzastaurin, 1 year after treatment start, in patients with relapsed DLBCL or transformed (CD20+) indolent lymphoma, who are older than 60 years. Patients who are younger than 60 may be included if they are not eligible for HDC followed by ASCT |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives: • Evaluation of best response (CR, CRu, PR, SD, progression) during R-GEMOX • Evaluation of progression free survival including Year 2 and Year 4 • Evaluation of overall survival including Year 1, Year 2, and Year 4 • Evaluation of event free survival including Year 1, Year 2 and Year 4 • Assess biomarkers relevant to enzastaurin and disease state and their correlation to clinical outcome; • Characterize pharmacokinetics of enzastaurin and its metabolite when administered in combination with R-GEMOX in the patients participating for safety assessment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients may be included in the study only if they meet all of the following criteria: [1] Histology diagnosis of DLBCL or transformed (CD20+) indolent lymphoma by the World Health Organization classification (Harris et al. 1999) at the time of relapse. In the case that histology diagnosis is not available, cytology diagnosis is accepted. [2] Performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale (see Protocol Attachment S013.6; Oken et al. 1982). [3] Have relapsed/progressed after CR, CRu or PR obtained in 1st or 2nd line treatment, or patients that have not progressed after SD obtained in 1st or 2nd line. [4] Prior treatment with at least one anthracycline-containing regimen. [5] Patients must have finished an interval of no less than 4 weeks from the completion of prior chemotherapy before receiving study treatment. [6] Measurable disease according to Cheson criteria (lymph node greater than 1.5 cm in its longest transverse diameter by CT scan) (see Protocol Attachment S013.5). [7] Estimated life expectancy of at least 12 weeks. [8] Patient compliance and geographic proximity that allow adequate follow-up. [9] Adequate organ function including the following: • Hepatic: total bilirubin < or = 1.5 times upper limit of normal (ULN); alanine transaminase (ALT) and aspartate transaminase (AST) < or = 2.5 times ULN; • Renal: serum creatinine <1.5 times ULN; • Adequate bone marrow reserve: platelets ≥75 x 109/L, absolute neutrophil count (ANC) ≥1.5 x 109/L. [10] 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 12 months after the study. Women with childbearing potential must have a negative serum pregnancy test within 3 days prior to study enrollment. [11] Have given informed consent. [12] ≥60 years or <60 (but ≥18 years) who are not eligible to HDC and ASCT. |
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: [13] 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. [14] Allogeneic transplantation. Prior autologous transplantation is allowed. [15] More than 2 prior anti-cancer treatment regimens. [16] Are pregnant or breastfeeding. [17] Central nervous system (CNS) metastases (unless the patient has completed successful local treatment for CNS metastases and has been off of corticosteroids for at least 4 weeks before starting study treatment). 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. [18] Have a serious concomitant systemic disorder (including active bacterial, fungal, or viral infection) that, in the opinion of the investigator, would compromise the safety of the patient and his/her ability to complete the study. [19] Human immunodeficiency virus (HIV) associated lymphomas. [20] 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. [21] 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 S013.4). [22] Inability to swallow tablets. [23] Previous exposure to gemcitabine or oxaliplatin. [24] Are unable to discontinue concurrent administration of carbamazepine, phenobarbital, or phenytoin. [25] Patients with grade 3-4 polineurophathy. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival at 1 year is the primary efficacy endpoint. Overall PFS time is defined as the time from the date of first treatment with study medication to the first date of disease progression or death from any cause. For patients not known to have died as of the data cut-off date and who do not have disease progression, overall PFS will be censored at the date of the last tumor assessment. For patients who receive subsequent anticancer treatment (after discontinuation from the study treatment) prior to disease progression, overall PFS will be censored at the date of the latest progression-free assessment prior to the initiation of subsequent treatment. |
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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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
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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Study closure will occur as soon as all patients have a last (4-year) follow-up assessment, i.e. the latest timepoint for study closure is 4 years after the last patient started treatment with study medication.
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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 | |
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 |