A Study of Enzastaurin in Participants With Follicular Lymphoma

Study Overview
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Brief Summary
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To evaluate the antitumor activity, as measured by tumor response rate, of enzastaurin in participants with Follicular Lymphoma (FL).

Official Title
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A Phase 2 Study of Enzastaurin in Participants With Follicular Lymphoma

Conditions
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Lymphoma, Follicular

Intervention / Treatment
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* Drug: Enzastaurin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants must: 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. Have Ann Arbor Stage III or IV disease. Must be chemo-naive 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 chemo-naive setting) is also allowed if completed at least 6 months prior to first dose of study treatment. Participants must not require cytoreductive therapy for at least 3 months from first dose of study treatment, in the opinion of the investigator. Previous radiation therapy is allowed, but should have been limited and must not have included whole pelvis radiation. Participants 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. Exclusion Criteria: Participants will be excluded from the study if they meet any of the following criteria: Are unable to swallow tablets. Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin. Are receiving concurrent administration of any other antitumor therapy. Are pregnant or breastfeeding. Have a serious concomitant systemic disorder (including active bacterial, fungal, or viral infection) that, in the opinion of the investigator, would compromise the participant's ability to adhere to the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzastaurin<br>Enzastaurin: 1125 milligram (mg) loading dose then 500 mg, oral daily, up to 3 years | Drug: Enzastaurin<br>* Administered orally<br>* Other names: LY317615;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response Rate (RR) (Percentage of Participants Exhibiting Complete Response [CR] or Complete Response Unconfirmed [CRu] or Partial Response [PR]) | Tumor response rate is defined as the number of responders divided by the number of treated patients. A responder is a patient who exhibits a complete response (CR), complete response unconfirmed (CRu), or partial response (PR) as defined by Cheson et al. CR, the disappearance of target lesions and any pathological lymph nodes [target or non-target] taking as reference the baseline sum of diameters in response to treatment; CRu, complete disappearance of all detectable clinical and radiographic evidence of disease, return of spleen to non-palpable if involved, residual lymph node mass greater than 1.5 centimeters (cm) has regressed by more than 75%; PR, 50% decrease in the sum of the products of the greatest diameter (SPD) of the 6 largest dominant masses, no increase of other nodes, liver or spleen and no new sites of disease. | Baseline to Measured Progressive Disease (up to 1559 Days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS is defined as the time from the date of study enrollment to the first date of measured progressive disease or death from any cause. For patients not known to have died as of the data cut-off date and who do not have objective progressive disease, PFS will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression or death, PFS will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation anticancer therapy. For reference, PFS will also be calculated and analyzed based on an alternative definition of censoring: for each patient who is not known to have died or to have had objective progression of disease as of the data cut-off date, PFS will be censored for that analysis at the date of last prior contact. | Baseline to Measured Progressive Disease or Death from Any Cause (Up to 1559 Days) | 
| Time to Response (TtR) | TtR is defined as the time from the date of study enrollment to the date of response (CR, CRu, or PR) for patients who have responded prior to receiving any subsequent anticancer therapy.CR, the disappearance of target lesions and any pathological lymph nodes [target or non-target] taking as reference the baseline sum of diameters in response to treatment; CRu, complete disappearance of all detectable clinical and radiographic evidence of disease, return of spleen to non-palpable if involved, residual lymph node mass greater than 1.5 centimeters (cm) has regressed by more than 75%; PR, 50% decrease in the sum of the products of the greatest diameter (SPD) of the 6 largest dominant masses, no increase of other nodes, liver or spleen and no new sites of disease. | Baseline to Date of Confirmed Response (Up to 890 Days) | 
| Duration of Response (DoR) | DoR is defined as the time from the date when the measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the date of first observation of measured progressive disease. For responding participants who die without progressive disease (including death from study disease), DoR will be censored at the date of death. For responding participants not known to have died as of the data cut-off date and who do not have progressive disease, DoR will be censored at the last objective progression-free assessment date prior to the data cut-off date. For responding participants who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to disease progression, DoR will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation anticancer therapy. | Time of Response to Measured Progressive Disease (Up to 1415 Days) | 
| Number of Participants With Response With Expression of Protein Biomarkers | Correlative analyses of tumor RR for PKC-β2 (protein kinase C-β) protein expression. Immunohistochemistry (IHC) staining was performed to assess protein expression of PKC-β2 in cytoplasm reported as H scores (logistic model of response rate), which was derived from a weighted average of staining intensity (scale 0 to 3, increasing intensity) and percentage of positive cells (0 to 100%) at each staining intensity. PKC-β2 expression was further classified into high vs. low expression using the cutpoint of the median of the distribution of PKC-β2 H scores. | Baseline |