| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| High-risk diffuse large B-cell lymphoma (DLBCL) |
|
| MedDRA Classification |
| 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 |
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. |
|
| 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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion 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 Bcell
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 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.) The 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 18 years of age.
[14] patients must receive on-study therapy no later than 90 days either
from their last cycle (Day 1) of induction therapy or from the last day
of consolidation radiotherapy. |
|
| E.4 | Principal exclusion 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. 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 nonmelanomatous
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 Protocol Attachment JCBJ.5).
[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. |
|
| E.5 End points |
| E.5.1 | 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. |
|
| 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 | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| 1. Health Related Quality of Life (EQ-5D) 2. Health Status (FACT-Lym) |
|
| 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 | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 80 |
| 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 |
|
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 10 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 10 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
Print
