high-risk diffuse large B-cell lymphoma (DLBCL ) MedDRA version: 14.1 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851
Conditions
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
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). Commonly accepted histological variants of DLBCL, such as immunoblastic lymphoma, primary mediastinal B-cell lymphoma, and T-cell rich B-cell lymphoma are allowed. [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, as judged by local radiologist and/or physician (an independent centralized radiology review will also be performed on these patients). Exceptions may be made (after consultation with the Lilly clinical research physician) for patients with PET-positive lesions in which a subsequent confirmation procedure (for instance, biopsy) reveals the lesion is not due to DLBCL. However, PET scans are not a required study procedure. (See Protocol Section 6.1.1 for more information.) [4] have completed six or eight 21-day cycles of R-CHOP, or six to eight 14-day cycles of R-CHOP as first-line therapy for DLBCL. (Refer to Section 5.5 for recommended regimens.) Patient must have achieved a CR or CRu (and have not subsequently progressed) according to International Workshop criteria (Cheson et al. 1999), or must be PET scan negative (according to Juweid et al. 2007), as judged by local radiologist and/or physician (an independent centralized radiology review will also be performed on these patients). Exceptions may be made (after consultation with the Lilly clinical research physician) for patients with PET-positive lesions in which a subsequent confirmation procedure (for instance, biopsy) reveals the lesion is not due to DLBCL. [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 1
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if they meet any of the following criteria: [15] 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. [16] receive concurrent administration of any other systemic anticancer therapy. Also, any systemic anti-cancer agent (for example, methotrexate or etoposide, and including investigational agents) initiated for treatment of DLBCL in combination with R-CHOP is not allowed. Patients who had been receiving chronic therapy such as hormonal therapy (for example, tamoxifen), low-dose (7.5 mg/week) methotrexate, or corticosteroids prior to the diagnosis and treatment of DLBCL, may continue to receive these therapies while on study, after agreement with the Lilly clinical research physician; however, initiation of these medications while the patient is on study is not allowed. Intrathecal prophylaxis is allowed. [17] have received radiation therapy to more than one targeted lesion (local residual disease) for treatment of lymphoma or have not recovered from the acute effects of radiation therapy prior to study entry. [18] are pregnant or breastfeeding. [19] 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. [20] have serious concomitant disorder, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the investigator). [21] are known to be HIV positive. [22] have a second primary malignancy (except adequately treated basal cell carcinoma of the skin or other cancer that is considered cured by surgical resection or radiation). Patients who had another malignancy in the past, but have been disease-free for more than 5 years, are eligible. [23] 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 Attachment JCBJ.5). It is recommended that patients with a prolonged QT interval corrected for heart rate (QTc) > 450/470 msec (males/females) at baseline on electrocardiogram (ECG), and patients who have a congenital long QT syndrome in their own or family medical history should be excluded, at the investigator’s discretion. It is recommended that QTc be calculated using Fridericia correction formula (QTcF; see Attachment JCBJ.10). A patient may still be entered on study with prolonged QT-interval only after discussion and agreement between the principal investigator and the Lilly clinical research physician. [24] are unable to swallow tablets. [25] requires use of carbamazepine, phenobarbital, or phenytoin (refer to Section 5.7). [26] prior stem cell or bone marrow transplantation. [27] a prior clinical history of an indolent lymphoma.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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;Secondary Objective: To compare time-to-event efficacy variables including rate of disease free survival at 2 years,event free survival between treatment arms,rate of event free survival at 2 years,overall survival time. To compare adverse events between treatment arms. To compare health-related quality of life using the FACT-Lym. To assess health status using the EQ-5D scale. To perform exploratory assessments of 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.;Primary end point(s): Overall Disease Free survival is the primary efficacy endpoint. 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. For patients not known to have died as of the data cut-off date and who do not have objectively determined disease recurrence, overall DFS will be censored at the date of the last objectively determined disease-free assessment. For patients who receive subsequent anticancer therapy (after discontinuation from the study therapy) prior to objectively determined disease recurrence, overall DFS will be censored at the date of the latest objectively-determined disease-free assessment prior to the initiation of subsequent therapy.;Timepoint(s) of evaluation of this end point: Last Patient Entered Treatment + 3 years (LPET+3 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Patients will continue to be followed for DFS for up to 5 years after LPET (LPET+5 years).;Timepoint(s) of evaluation of this end point: LPET+5 years | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, India, Italy, Japan, Korea, Republic of, Mexico, Poland, Portugal, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Eli Lilly
Outcome results
None listed