A study of experimental drug called enzastaurin in patients who have a type of cancer that effects the lymph system called follicular lymphoma.

• Conditions: Grade 1 or 2 follicular lymphoma; MedDRA version: 17.1Level: PTClassification code 10003899Term: B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 17.1Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 17.1Level: LLTClassification code 10029473Term: Nodular (follicular) lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 17.1Level: HLTClassification code 10003900Term: B-cell lymphomas NECSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2007-006246-17-DE
• Lead Sponsor: Eli Lilly and Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-04-23
• Last Update Posted: 2 March 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Patients are eligible to be included in the study only if they meet all of the following
criteria:
[1] Have had a histologically confirmed diagnosis of Grade 1 or 2 FL, according to World Health Organization classification (Harris et al.1999), at the original time of diagnosis. Pathology must be confirmed locally prior to enrollment at the investigational site.
[2] Have Ann Arbor Stage III or IV disease (see Protocol Attachment S011.4).
[3] Must be chemonaive OR have relapsed disease after receiving only one prior chemotherapy regimen. The chemotherapy must have been completed at least 6 months prior to first dose of study treatment. Relapse after one prior course of single-agent rituximab treatment (in the chemonaive setting) is also allowed if completed at least 6 months prior to first dose of study treatment.
[4] Patients must not require cytoreductive therapy for at least 3 months from first dose of study treatment, in the opinion of the investigator.
[5] Previous radiation therapy is allowed, but should have been limited and must not have included whole pelvis radiation. Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed 30 days before study entry. Lesions that have been
irradiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy.
[6] Have measurable disease as defined by International Working Group recommendations (Cheson et al. 1999; Protocol Attachment S011.5).
[7] Have adequate organ function including the following:
• Adequate bone marrow reserve: absolute neutrophil count (ANC) =1.5 × 109/L, platelet count =75.0 × 109/L, and hemoglobin >9.0 g/dL.
• Hepatic: bilirubin =1.5 times the upper limit of normal (× ULN); aspartate transaminase (AST) and alanine transaminase (ALT) =2.5 × ULN, or AST and ALT <5 × ULN with liver metastases.
• Renal: serum creatinine =1.5 × ULN.
[8] Have an estimated life expectancy of at least 12 weeks.
[9] Patient compliance and geographic proximity that allow for adequate follow-up.
[10] Patients must sign an informed consent document for the study including consent for all pharmacogenomic sampling.
[11] Patients must be at least 18 years of age.
[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 =7 days prior to study enrollment.
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 13
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion Criteria

Patients will be excluded from the study if they meet any of the following criteria:
[13] Are unable to swallow tablets.
[14] Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin (refer to Section 5.7.1).
[15] Are receiving concurrent administration of any other antitumor therapy.
[16] Are pregnant or breastfeeding.
[17] Have a serious concomitant systemic disorder (including active bacterial, fungal, or viral infection) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol.
[18] 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 S011.7).
[19] Have any tumor mass >10cm.
[20] Have B” symptoms: unexplained weight loss (>10%), unexplained fever (> 38°C or 100.4°F), or night sweats.
[21] Have Grade 3 FL, or transformed lymphoma.
[22] Are human immunodeficiency virus (HIV) positive.
[23] Have a prior malignancy (other than FL, 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.
[24] 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.
[25] 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.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Evaluation of the primary analysis (RR) will occur after all patients have progressed, have died, have been lost to follow up, or have been followed for at least 12 months from start of study treatment. ;Main Objective: To evaluate the antitumor activity, as measured by tumor response rate of enzastaurin in patients with follicular lymphoma.;Primary end point(s): The primary outcome measure is the tumor response rate. A response rate of 20% (CI 95%, 10.8% to 32.3%) would be considered a clinically meaningful response in the study.;Secondary Objective: To assess the following efficacy variables:<br>- Progression-free survival (PFS)<br>- Time to response (TtR)<br>- Duration of response (DoR).<br><br>To evaluate the safety of enzastaurin in this patient population.<br><br>To assess biomarkers relevant to enzastaurin and the disease state, as well<br>as their correlation to clinical outcomes.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Progressive Free Survival (PFS) and Duration of Response (DoR) will be calculated, endpoint not defined. ;Timepoint(s) of evaluation of this end point: At same time of the primary analysis.