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

Phase 2
Completed
Conditions
Non-Hodgkin's Lymphoma
Interventions
Registration Number
NCT00042666
Lead Sponsor
Eli Lilly and Company
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
55
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
LY317615LY317615500 milligrams (mg), oral, daily (QD), up to six (6) 28-day cycles
Primary Outcome Measures
NameTimeMethod
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)Randomization to measured progressive disease (PD) up to 34.3 months

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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate)Randomization to measured PD or death up to 34.3 months

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.

Progression Free Survival (PFS)Randomization to PD or death due to any cause up to 34.3 months

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.

Duration of Overall Response (DOR)Time of response to PD up to 34.3 months

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).

Number of Participants With Adverse Events (AEs) or Who DiedRandomization to study completion [Baseline up to 37 cycles (28-day cycles, 34.3 months) and 30-day follow-up]

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.

Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval (AUC0-24,ss) of Enzastaurin and Its Metabolite LY326020Cycle 1 Day 1 predose, 1 to 4 hours postdose and Cycle 1 Day 28 predose and at least 1-hour postdose (28-day cycle)

AUC0-24,ss during 1 dosing interval at steady state for Enzastaurin and its metabolite LY326020.

PKCβ Expression by IHC in Readily Assessable DLBCL Tumors From ParticipantsBaseline

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.

Trial Locations

Locations (1)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

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Rochester, Minnesota, United States

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