A Study for Patients With Non-Hodgkin's Lymphomas

Study Overview
=================
Brief Summary
-----------------
In this study, all patients will get investigational drug. There will be no comparator drug. This study will evaluate three tumor types: T-cell lymphoma, Indolent B-cell lymphoma, and Aggressive B-cell lymphoma. Each tumor type will include several tumor subtypes: T-cell lymphoma: Peripheral and Cutaneous T-cell lymphoma (PTCL, CTCL) Indolent B-cell lymphoma: Small lymphocytic lymphoma, follicular lymphoma (Gr 1 or 2) and marginal zone lymphoma Aggressive B-cell lymphoma: Primary CNS lymphoma, follicular lymphoma (Gr 3a and 3b) and aggressive lymphoma with prior clinical history of indolent lymphoma.

Official Title
-----------------
A Multicenter, Open-label, Noncomparative Study of Enzastaurin in Patients With Non-Hodgkin's Lymphomas

Conditions
-----------------
T-Cell Lymphoma, B-Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: enzastaurin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have measurable lesions Have recovered from prior chemotherapies Have an estimated life expectancy of at least 12 weeks Hepatic: total bilirubin less than or equal to 1.5 XULN; ATL/AST less than or equal to 2.0 x ULN (less than 5x if liver metastases are present) Renal: serum creatinine less than or equal to 1.5XULN Adequate bone marrow reserve: platelets greater than or equal to 75 x 109 /Liter (L) Criteria: Have a second primary malignancy (except adequately treated nonmelanomatous skin cancer, or other cancer that is considered cured by surgical resection or radiation). Anti-lymphoma therapy within the past 3 weeks Unable to swallow tablets Unable to discontinue use of carbamazepine, phenobarbital and phenytoin at least 14 days prior to study enrollment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T-Cell<br>T-Cell (TCL): Peripheral and cutaneous T-cell lymphoma (PTCL, CTCL). Participants received enzastaurin 1125 milligram (mg) loading dose then 500 mg, oral, daily until progressive disease or predefined criteria for discontinuation is met. Participants who progress within the first 28 days may remain on study treatment, provided that the participant is not in need of immediate treatment with another anticancer therapy. Study treatment occurs in cycles. 1 cycle = 28 days | Drug: enzastaurin<br>* 1125 mg loading dose then 500 mg, oral, daily until progressive disease<br>* Other names: LY317615;|
| Experimental: Indolent B-Cell<br>Indolent B-Cell (IBCL): Small lymphocytic lymphoma, follicular lymphoma (Grade 1 or 2) and marginal zone lymphoma. Participants received enzastaurin 1125 mg loading dose then 500 mg, oral, daily until progressive disease or predefined criteria for discontinuation is met. Participants who progress within the first 28 days may remain on study treatment, provided that the participant is not in need of immediate treatment with another anticancer therapy. Study treatment occurs in cycles. 1 cycle = 28 days | Drug: enzastaurin<br>* 1125 mg loading dose then 500 mg, oral, daily until progressive disease<br>* Other names: LY317615;|
| Experimental: Aggressive B-Cell<br>Aggressive B-Cell (ABCL): Primary central nervous system (CNS) lymphoma, follicular lymphoma (Grade 3a and 3b) and aggressive lymphoma with prior clinical history of indolent lymphoma. Participants received enzastaurin 1125 mg loading dose then 500 mg, oral, daily until progressive disease or predefined criteria for discontinuation is met. Participants who progress within the first 28 days may remain on study treatment, provided that the participant is not in need of immediate treatment with another anticancer therapy. Study treatment occurs in cycles. 1 cycle = 28 days | Drug: enzastaurin<br>* 1125 mg loading dose then 500 mg, oral, daily until progressive disease<br>* Other names: LY317615;|

What is the study measuring?
-----------------
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 RR is defined as the number of responders divided by the number of treated participants for that tumor subtype. A responder was a participant who exhibited: a CR defined as a modified severity-weighted assessment tool (mSWAT) value of zero or a partial response (PR) defined as a mSWAT value > 50% decrease from baseline [for participants with cutaneous T-cell lymphoma (CTCL) using the mSWAT or CR, unconfirmed CR (Cru), or PR as defined by Abrey et al., (2005) (for participants with central nervous system (CNS) Lymphoma); or for all other participants a CR or complete response - unconfirmed (CRu) or PR as defined by Cheson et al., (1999). | Baseline to Measured Progressive Disease (Up to 114 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Progression-free survival is defined as the time from the date of study enrollment to the first date of objectively determined progressive disease or death from any cause. Progressive disease (PD) is an increase of Sézary cell percentage by greater than or equal to 40% in cluster of differentiation (CD4+/CD7- or 30% in CD4+/CD26- as compared to each respective nadir. mSWAT, primary central nervous system lymphoma (PCSNSL) and International Workshop Response Criteria (IWRC) response criteria were used for CTCL, primary central nervous system lymphoma (CNSL) and all other participants respectively. PFS was censored at the date of the last objective progression-free assessment. | Baseline to Measured Progressive Disease or Death From Any Cause (Up to 114 Months) | 
| Time to Progressive (TTP) Disease | TTP disease is defined as the time from the date of study enrollment to the date of objectively determined disease progression. Objectively determined progressive disease (PD) was interpreted as meeting the criteria for PD. For patients who died without documented objective PD (including death from study disease); TTP was censored at the date of the last objective progression-free disease assessment prior to death. For participants not known to have died as of the data cut-off date and who did not have objective PD, TTP was censored at the date of the last objective progression-free disease assessment. For participants who received subsequent anticancer therapy (after discontinuation from study treatment) prior to objectively determined disease progression, TTP was censored at the date of the last objective progression free disease assessment prior to post-discontinuation therapy. | Baseline to Measured Progressive Disease (Up to 114 Months) | 
| Duration of Response (DOR) | DoR is defined as the time from the date when the measurement criteria were met for CR, CRu, or PR (whichever status was recorded first) until the date of first observation of objectively determined disease progression (CR, CRu, or PR see above definition of responder). For responding participants who died without PD (including death from study disease), DoR was censored at the last assessment demonstrating lack of progression. For responding patients not known to have died as of the data cut-off date and who did not have PD, DoR was censored at the last assessment demonstrating objective response prior to the data cut-off date. For responding participants who received subsequent anticancer therapy (after discontinuation from the study treatment) prior to disease progression, DoR was censored at the last assessment demonstrating objective response prior to the initiation of post-discontinuation anticancer therapy. | Baseline to Measured Progressive Disease (Up to 97 Months) | 
| Percentage of Participants With Progression Free Survival (PFS) at 1-Year | PFS at 1 year was defined as the probability of being alive and having not progressed at 1 year and calculated from the PFS Kaplan-Meier analysis. PFS was censored at the date of the last objective progression-free assessment. Progressive disease (PD) is an increase of Sézary cell percentage by greater than or equal to 40% in cluster of differentiation (CD4+/CD7- or 30% in CD4+/CD26- as compared to each respective nadir. mSWAT, primary central nervous system lymphoma (PCSNSL) and International Workshop Response Criteria (IWRC) response criteria were used for CTCL, primary central nervous system lymphoma (CNSL) and all other participants respectively. PFS was censored at the date of the last objective progression-free assessment. | Baseline to Measured Progressive Disease or Death From Any Cause (1 Year) | 
| Number of Participants With One or More Drug-Related Adverse Events | Number of participants with one or more Drug-Related Adverse Events. Clinically significant events are defined as serious adverse events, regardless of causality. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module. | Baseline to End of Study (Up to 114 Months) |