A Study of Oral LY317615 in Relapsed or Refractory Diffuse Large B-Cell Lymphomas.

Study Overview
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Brief Summary
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This study will measure the effectiveness and any side effects of LY317615 in participants with diffuse large B-cell lymphoma (DLBCL: a sub-type of Non-Hodgkins Lymphoma).

Official Title
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A Phase 2 Evaluation of Oral LY317615 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: LY317615


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of recurrent or refractory DLBCL. Adequate organ functions. Able to swallow capsules. Exclusion Criteria: More than 3 prior treatments for this disease. Serious heart problems.

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: LY317615<br>500 milligrams (mg), oral, daily (QD), up to six (6) 28-day cycles | Drug: LY317615<br>* 500 mg, oral, QD, up to six 28 day cycles<br>* Other names: enzastaurin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Relapsed or Refractory DLBCL Who Are Progression-Free for at Least 2 Cycles (28-Day Cycles) After Receiving Enzastaurin (LY317615) (Clinical Response Rate) | Clinical Response Rate in participants with DLBCL was calculated as (number of participants who were progression-free for at least two 28-day cycles [clinical responder]) divided by (total number of participants analyzed) multiplied by 100. Progression free survival (PFS) defined as the time from randomization to the first observation of disease progression or death due to any cause. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0) as 20% increase in the sum of the of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Randomization to measured progressive disease (PD) up to 34.3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate) | Overall response rate was defined as best study response (CR or PR) using modified Southwest Oncology Group (SWOG) Response criteria. CR defined as the disappearance of detectable clinical and radiographic evidence of disease; regression of lymph nodes, nodal masses and spleen to normal size and absence of lymphoma in bone marrow infiltrate. PR was defined as a ≥50% decrease in the sum of the products of their diameters (SPD) in the 6 largest dominant nodes or nodal masses; no increase in size in the other nodes or liver or spleen; regression of nodes/lesions in organs by ≥50% in the SPD; or no new disease sites. The percentage participants was calculated as: (number of participants with CR or PR) divided by (number of participants qualified for tumor response analysis) multiplied by 100. | Randomization to measured PD or death up to 34.3 months | 
| Progression Free Survival (PFS) | PFS was defined as the time from randomization to the first observation of disease progression or death due to any cause. For participants not known to have died as of the data cut-off date and who did not have PD, PFS was censored at the date of last follow-up visit. Progression is determined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0) as 20% increase in the sum of the of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Randomization to PD or death due to any cause up to 34.3 months | 
| Duration of Overall Response (DOR) | Duration of CR or PR was defined as the time from first objective assessment to first time of disease progression or death from any cause using the modified SWOG Response criteria. CR defined as the disappearance of detectable clinical and radiographic evidence of disease, regression of lymph nodes, nodal masses and spleen to normal size and absence of lymphoma in bone marrow infiltrate. PR was defined as a ≥50% decrease in the SPD in the 6 largest dominant nodes or nodal masses, no increase in size in the other nodes, liver or spleen, regression of nodes/lesions in organs by ≥50% in the SPD, and no new disease sites. PD defined as >50% increase in SPD of the dominant nodal/non-nodal sites or new lesions. For participants who died, the duration of response was censored at death. For participants still alive, duration of overall response was censored at the last visit or follow-up visit. DOR was not analyzed due to low number of responders (CR or PR). | Time of response to PD up to 34.3 months | 
| Number of Participants With Adverse Events (AEs) or Who Died | Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs. Participants who died due to PD, AEs while on treatment or died during the 30-day post-treatment period are included. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Randomization to study completion [Baseline up to 37 cycles (28-day cycles, 34.3 months) and 30-day follow-up] | 
| Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval (AUC0-24,ss) of Enzastaurin and Its Metabolite LY326020 | AUC0-24,ss during 1 dosing interval at steady state for Enzastaurin and its metabolite LY326020. | Cycle 1 Day 1 predose, 1 to 4 hours postdose and Cycle 1 Day 28 predose and at least 1-hour postdose (28-day cycle) | 
| PKCβ Expression by IHC in Readily Assessable DLBCL Tumors From Participants | Protein expression was measured (cytoplasmic staining) using an IHC assay from a small subset of tumor tissue samples that were scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system, where higher staining indicated a greater PKCβ expression. | Baseline |