PRELUDE: Study to Investigate the Prevention of Relapse in Lymphoma Using Daily Enzastauri

• Conditions: High-risk Diffuse Large B-cell Lymphoma (DLBCL ); Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 14.1Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851

• Registration Number: EUCTR2005-004630-41-HU
• Lead Sponsor: Eli Lilly and Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-02-16
• Last Update Posted: 2 September 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 709

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 Protocol 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 to 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 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 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

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 non-melanomatous skin cancer, 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 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 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified