PRELUDE:Study to Investigate the Prevention of Relapse in Lymphoma Using Daily Enzastaurin

Study Overview
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Brief Summary
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This clinical research study is to investigate the prevention of relapse in patients with diffuse large B cell lymphoma (DLBCL) using enzastaurin daily. This is a randomised trial which compares Enzastaurin to Placebo (dummy treatment), the chance of receiving Enzastaurin is 2 to 1.

Official Title
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A Phase 3 Clinical Study to Investigate the Prevention of Relapse in Lymphoma Using Daily Enzastaurin

Conditions
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Non Hodgkin Lymphoma

Intervention / Treatment
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* Drug: enzastaurin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of diffuse large B cell lymphoma Recently completed R-CHOP therapy and achieved remission International Prognostic Index (IPI) score 3,4,5 At least 18 years of age Agree to study follow-up schedule Exclusion Criteria: Have received therapy other than R-CHOP for lymphoma Serious medical condition such as infection,second cancer,heart disease Received radiation to more than one lesion Unable to swallow tablets

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: enzastaurin<br>* 1125 mg loading dose then 500 mg, oral, daily, until disease progression or maximum of 3 years<br>* Other names: LY317615;|
| Placebo Comparator: B<br> | Drug: placebo<br>* oral, daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Disease-Free Survival | Overall Disease-Free Survival (DFS) time is defined as the time from the date of study enrollment to the first date of objectively determined disease recurrence (progressive disease) or death from any cause. DFS was assessed according to International Working Group recommendations. Progressive disease (PD) is defined as a ≥ 50% increase from the lowest point in the sum of the product of the diameters (SPD) of any previously identified abnormal node for partial or nonresponders, or the appearance of any new lesion during or at the end of therapy. | Baseline to Measured Progressive Disease or Death from Any Cause (up to 80.30 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival at 2 Years | Disease-free survival at 2 years (DFS2) is defined as the rate of DFS at 2 years from the date of study enrollment and is determined using the distribution of overall DFS times. Disease-free survival rates at 2 years will be estimated using the Kaplan-Meier method. | Baseline to 2 Years | 
| Event-Free Survival | Overall Event-Free Survival (EFS) time is defined as the time from the date of study enrollment to the first date of objectively determined disease recurrence (progressive disease), institution of a new anti-cancer treatment, or death from any cause. Progressive disease (PD) is defined as a ≥ 50% increase from the lowest point in the sum of the product of the diameters (SPD) of any previously identified abnormal node for partial or nonresponders, or the appearance of any new lesion during or at the end of therapy. | Baseline to Objective PD, Start of New Therapy or Death From Any Cause (up to 76.81 months) | 
| Event-Free Survival at 2 Years | Event-Free Survival at 2 years (EFS2) is defined as the rate of EFS at 2 years from the date of study enrollment and is determined using the distribution of overall EFS times. Event-free survival rates at 2 years will be estimated using the Kaplan-Meier method. | Baseline to 2 Years | 
| Overall Survival | Overall survival (OS) time is defined as the time from the date of study enrollment to the date of death from any cause. | Baseline to Date of Death from Any Cause (up to 80.30 months) | 
| Number of Participants With Treatment-Emergent Adverse Events | Number of participants with treatment-emergent adverse events. | First dose through 30 days post-study treatment discontinuation (up to 81.30 months) | 
| Quality of Life: Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Score | The FACT-Lym assesses health-related quality of life (HRQoL) in participants with non-Hodgkin lymphoma. It includes the 27-item cancer-specific FACT-G (General), which assesses physical, social/family, emotional and functional well-being, plus a 15-item subscale that assesses concerns specific to lymphoma. Each item is scored on a scale from 0 (not at all) to 4 (very much), yielding a possible score of 0-168, with higher scores representing better HRQoL. This analysis utilized mixed-effect model repeated measure (MMRM) analysis of change from baseline adjusting for baseline covariates. | Baseline, Month 2; Baseline, Month 4; Baseline, Month 6; Baseline, Month 12; Baseline, Month 18; Baseline, Month 24; Baseline, Month 36 | 
| Change From Baseline in EuroQol-5D (EQ-5D) Score | The EQ-5D instrument is a participant-rated questionnaire used to evaluate health status. The EQ-5D assesses five dimensions (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression) that participants rate using three levels (no problem, some problem, or extreme problem), as well as overall health status. The five dimensions can be combined using country-specific weights to create an estimate of overall health status score. The possible values for score range from -0.594 (severe problems in all 5 dimensions) to 1 (no problem in all dimensions) on a scale where 1 represents the best possible health state. This analysis utilized mixed-effect model repeated measure (MMRM) analysis of change from baseline in the EQ-5D for the United Kingdom population-based index score adjusting for baseline covariates. | Baseline, Month 6; Baseline, Month 24; Baseline, Month 33 | 
| Translational Research: DFS Participants With Diffuse Large B-cell Lymphoma (DLBCL) Germinal-center B-cells (GCB) Versus Non-germinal-center B-cells | Reported are the DFS for GCB and non-GCB status. DLBCL molecular subtypes of GCB/non-GCB using Hans' algorithm were determined by protein expression by immunohistochemistry (IHC) staining was used to assess molecular subtype characterization of GCB and non-GCB. | Baseline to 24 months (2 years) | 
| Translational Research: DFS of Participants With Diffuse Large B-cell Lymphoma (DLBCL) Protein Kinase C-β2 (PKC-β2) Expression | Reported are the DFS based on PKC-β2 protein expression. Immunohistochemistry (IHC) staining was performed to assess protein expression of PKC-β2 in cytoplasm scored for percent of tumor cells stained, and using 50% positive staining as the cutoff for high/low expression (high expression: >=50% staining, low expression: <50% staining). | Baseline to 94.5 months | 
| Pharmacokinetics: Average Steady-State Concentration (Cavg,ss) for Total Analyte |  | Month 2, Month 4: Predose |