| ID | Type | Description | Link |
|---|---|---|---|
| H6Q-MC-JCAI | Other Identifier | Eli Lilly and Company |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY317615 | Experimental | 500 milligrams (mg), oral, daily (QD), up to six (6) 28-day cycles |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY317615 | Drug | 500 mg, oral, QD, up to six 28 day cycles |
|
|
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 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. | Royal Oak | Michigan |
Participant Flow is reporting participants who discontinued from study drug. Per the protocol, a participant completed the study if the planned duration of treatment (6 cycles) was completed in the absence of disease progression or other reasons for discontinuation.
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| ID | Title | Description |
|---|---|---|
| FG000 | Enzastaurin | 500 milligrams (mg) enzastaurin (LY317615) tablets were administered in the morning within 30 minutes following a meal for 28 days (1 cycle) to be continued for up to 6 cycles in the absence of disease progression. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Enzastaurin | 500 mg enzastaurin (LY317615) tablets were administered in the morning within 30 minutes following a meal for 28 days (1 cycle) to be continued for up to 6 cycles in the absence of disease progression. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All randomized participants who remained on study for at least 1 cycle of treatment. | Posted | Number | 95% Confidence Interval | percentage of participants | Randomization to measured progressive disease (PD) up to 34.3 months |
|
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Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Enzastaurin | 500 mg enzastaurin tablets were administered in the morning within 30 minutes of a meal for 28 days (1 cycle) to be continued for up to 6 cycles in the absence of disease progression. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 16.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 16.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
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| ID | Term |
|---|---|
| C504878 | enzastaurin |
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| 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 |
| United States |
| 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. | Minneapolis | Minnesota | United States |
| 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. | Rochester | Minnesota | United States |
| Participant/Physician Perception |
|
| Progressive Disease |
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| Other |
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| Other |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
| PKCβ expression by IHC in DLBCL Tumors | Protein Kinase C Beta (PKCβ) and Diffuse Large B-Cell Lymphoma (DLBCL). Protein expression was measured using an Immunohistochemistry (IHC) assay from tumor tissue samples that were scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic and nuclear staining. Three (3) participants had diagnostic tissue samples available for assay. | Count of Participants | Participants | No |
|
| OG000 |
| Enzastaurin |
500 mg enzastaurin (LY317615) tablets were administered in the morning within 30 minutes following a meal for 28 days (1 cycle) to be continued for up to 6 cycles in the absence of disease progression. |
|
|
| Secondary | 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. | All randomized participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | Randomization to measured PD or death up to 34.3 months |
|
|
|
| Secondary | 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. | All randomized participants who received at least 1 dose of study drug. Five (5) participants were censored. | Posted | Median | 95% Confidence Interval | months | Randomization to PD or death due to any cause up to 34.3 months |
|
|
|
| Secondary | 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). | Zero participants were analyzed. | Posted | Median | 95% Confidence Interval | months | Time of response to PD up to 34.3 months |
|
|
|
| Secondary | 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. | All randomized participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | No | Randomization to study completion [Baseline up to 37 cycles (28-day cycles, 34.3 months) and 30-day follow-up] |
|
|
|
| Secondary | 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. | All randomized participants who received at least 1 dose of study drug and had evaluable PK data to calculate AUC0-24,ss. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomoles*hour per liter (nmol*h/L) | 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) |
|
|
|
| Secondary | 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. | Participants who had paired diagnositic and relapsed tumor assessed for PKCβ expression. | Posted | Number | participants | Baseline |
|
|
|
| 21 |
| 55 |
| 51 |
| 55 |
| Angina unstable | Cardiac disorders | 16.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Asthenia | General disorders | 16.0 | Systematic Assessment |
|
| Fatigue | General disorders | 16.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | 16.0 | Systematic Assessment |
|
| Pyrexia | General disorders | 16.0 | Systematic Assessment |
|
| Clostridium difficile sepsis | Infections and infestations | 16.0 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | 16.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | 16.0 | Systematic Assessment |
|
| Pneumonia pneumococcal | Infections and infestations | 16.0 | Systematic Assessment |
|
| Septic shock | Infections and infestations | 16.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | 16.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | 16.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | 16.0 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | 16.0 | Systematic Assessment |
|
| Syncope | Nervous system disorders | 16.0 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | 16.0 | Systematic Assessment |
|
| Azotaemia | Renal and urinary disorders | 16.0 | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | 16.0 | Systematic Assessment |
|
| Ureteric obstruction | Renal and urinary disorders | 16.0 | Systematic Assessment |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | 16.0 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 16.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | 16.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | 16.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Asthenia | General disorders | 16.0 | Systematic Assessment |
|
| Chills | General disorders | 16.0 | Systematic Assessment |
|
| Fatigue | General disorders | 16.0 | Systematic Assessment |
|
| Oedema | General disorders | 16.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | 16.0 | Systematic Assessment |
|
| Pyrexia | General disorders | 16.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | 16.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | 16.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | 16.0 | Systematic Assessment |
|
| Weight decreased | Investigations | 16.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | 16.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | 16.0 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | 16.0 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | 16.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | 16.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | 16.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | 16.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | 16.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | 16.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | 16.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | 16.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | 16.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | 16.0 | Systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | 16.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | 16.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 16.0 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | 16.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | 16.0 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | 16.0 | Systematic Assessment |
|
Not provided
| D008206 |
| Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| Title | Measurements |
|---|---|
|
| Deaths Due to AEs |
|
| Deaths in 30-day follow-up |
|
| Title | Measurements |
|---|---|
|