An Open-label, Randomized, Phase 2 Study of R-CHOP Plus Enzastaurin versus R-CHOP in the First-Line Treatment of Patients with Intermediate and High-Risk Diffuse Large B-Cell Lymphoma - N/A

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-005496-10-IE
• Date of registration: 11/09/2008
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: An Open-label, Randomized, Phase 2 Study of R-CHOP Plus Enzastaurin versus R-CHOP in the First-Line Treatment of Patients with Intermediate and High-Risk Diffuse Large B-Cell Lymphoma - N/A
• Scientific title: An Open-label, Randomized, Phase 2 Study of R-CHOP Plus Enzastaurin versus R-CHOP in the First-Line Treatment of Patients with Intermediate and High-Risk Diffuse Large B-Cell Lymphoma - N/A
• Date of first enrolment: 28/01/2009
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005496-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Ireland

Key inclusion & exclusion criteria

Inclusion criteria:
Patients are eligible to be included in the study only if they meet all of the following
criteria:
[1] Have a histologically confirmed diagnosis of DLBCL based on 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 with a prior history of an indolent lymphoma or a histological diagnosis of follicular Grade 3 lymphoma will not be
eligible for enrollment.
[2] Have received no prior chemotherapy.
[3] Have an IPI score =2 at time of original diagnosis (Protocol Attachment S028.5).
[4] Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology group (ECOG) scale (Protocol Attachment S028.4; Oken et al. 1982).
[5] Have adequate organ function as follows:
• Hepatic: total bilirubin =1.5 times the upper limit of normal (× ULN); alanine transaminase (ALT) and aspartate transaminase (AST) =1.5 × ULN, (=5 × ULN, if liver involvement).
• Renal: serum creatinine =1.5 × ULN
• Adequate bone marrow reserve: platelets =75 × 109/L, absolute neutrophil count (ANC) =1.0 × 109/L, unless there is bone marrow involvement.
[6] Have a normal left ventricular ejection fraction of =50% by echocardiography or nuclear medicine multi-gated (MUGA) scan.
[7] Are at least 18 years of age.
[8] 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 =3 days prior to study enrollment.
[9] Must agree to participate in PGx sampling and analysis.
[10] Have an estimated life expectancy of at least 12 weeks.
[11] Must sign an informed consent document (or legal representative has given informed consent).
[12] Exhibit patient compliance and geographic proximity that allow for adequate follow-up.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 (not including enzastaurin) that has not received regulatory approval for any indication at the time of study entry.
[14] Are receiving concurrent administration of any other systemic anticancer therapy.
[15] Are pregnant or breastfeeding.
[16] Are unable to swallow tablets.
[17] Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin at least 14 days prior to study enrollment (Protocol Attachment S028.3).
[18] Have a serious concomitant systemic disorder, including active bacterial or fungal infection, incompatible with the study (at the discretion of the investigator).
[19] Have human immunodeficiency virus (HIV) associated lymphomas.
[20] 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 (Protocol Attachment S028.6).
[21] Have a prior malignancy (other than DLBCL, or adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer), unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence.
[22] Have central nervous system (CNS) metastases. A screening CT or MRI before enrollment in the absence of a clinical suspicion of brain metastases is not required.
[23] Have previously received enzastaurin therapy in any other clinical trial


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

First-Line Diffuse Large B-Cell Lymphoma
MedDRA version: 9.1 Level: LLT Classification code 10012855 Term: Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation)

Intervention(s)

Product Name: Enzastaurin
Product Code: LY317615
Pharmaceutical Form: Tablet
INN or Proposed INN: Enzastaurin Hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-

Primary Outcome(s)

Secondary Objective: The secondary objectives of the study are as follows:
• to compare R-CHOP plus enzastaurin versus R-CHOP in terms of
complete response (CR) and/or unconfirmed CR (CRu) rate, and overall
response rate (ORR)
• to compare R-CHOP plus enzastaurin versus R-CHOP in terms of the
2-year PFS rate
• to evaluate the PET-negative rates for each treatment arm
• to investigate concordance between CT/MRI assessment and PET scan
• to evaluate the following time-to-event efficacy variables for each
treatment arm:
- event-free survival (EFS)
- overall survival (OS)
- duration of complete response
• to assess biomarkers relevant to enzastaurin and the disease state, as well as their
correlation to clinical outcome
• to evaluate toxicity and tolerability of R-CHOP plus enzastaurin

Main Objective: To compare R-CHOP plus enzastaurin versus R-CHOP in terms of the elapsed
progression-free survival (PFS) time measured in patients with intermediate and/or
high-risk DLBCL receiving first-line treatment.

Primary end point(s): The primary endpoint for this study is progression-free survival

Secondary ID(s)

H6Q-MC-S028