A Study of Participants With Lymphoma Who Take R-CHOP and Enzastaurin Compared to Participants Who Take R-CHOP Only

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00451178
• Collaborator: (none)
• Enrollment: 101
• Locations: 25
• Arms: 2
• Duration (Months): 68.1
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To compare R-CHOP plus enzastaurin versus R-CHOP for progression-free survival (PFS) time measured in participants with intermediate and/or high risk for diffuse large B-cell lymphoma (DLBCL) receiving first-line treatment.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: enzastaurin; Drug: rituximab; Drug: cyclophosphamide; Drug: doxorubicin; Drug: vincristine; Drug: prednisone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomized, Phase 2 Study of R-CHOP Plus Enzastaurin Versus R-CHOP in the First-Line Treatment of Patients With Intermediate and High-Risk Diffuse Large B-Cell Lymphoma
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R-CHOP and Enzastaurin R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.	Drug: enzastaurin; 1125 milligrams (mg) then 500 mg, oral, daily, six 21-day cycles or up to 3 years; Other Names: LY317615 ; Drug: rituximab; 375 milligrams per square meter (mg/m^2), intravenous (IV), Day 1 every 21 days, six 21-day cycles; Drug: cyclophosphamide; 750 mg/m^2, IV, Day 1 every 21 days, six 21-day cycles; Drug: doxorubicin; 50 mg/m^2, IV, Day 1 every 21 days, six 21-day cycles; Drug: vincristine; 1.4 mg/m^2, IV, Day 1 every 21 days, six 21-day cycles; Drug: prednisone; 100 mg, oral, Days 1-5, six 21-day cycles
Active Comparator: R-CHOP R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.	Drug: rituximab; 375 milligrams per square meter (mg/m^2), intravenous (IV), Day 1 every 21 days, six 21-day cycles; Drug: cyclophosphamide; 750 mg/m^2, IV, Day 1 every 21 days, six 21-day cycles; Drug: doxorubicin; 50 mg/m^2, IV, Day 1 every 21 days, six 21-day cycles; Drug: vincristine; 1.4 mg/m^2, IV, Day 1 every 21 days, six 21-day cycles; Drug: prednisone; 100 mg, oral, Days 1-5, six 21-day cycles

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) Time [Randomization to measured PD or death from any cause (up to 55 months)]

   PFS time is the elapsed time from the date of randomization to the first date of objectively-determined PD or death from any cause. PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. For participants not known to have died as of the data cut-off date and who did not have objective PD, PFS was censored at the date of the last objective progression-free disease assessment. For participants who received subsequent anticancer therapy (other than enzastaurin maintenance therapy) prior to objectively determined disease progression or death, PFS was censored at the date of the last objective progression-free disease assessment prior to the date of subsequent therapy.

Secondary Outcome Measures

1. Percentage of Participants With Complete Response (CR and CRu) and Objective Response [CR, CRu, and Partial Response (PR)] (Overall Response Rate) [Baseline through long-term follow-up (up to 2 years post last dose)]

   CR, CRu, and PR were defined using International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow. PR is a 50% decrease in the sum of the products of diameters for up to 6 identified dominant lesions, including splenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. The percentage of participants with complete response (CR/CRu) and objective response (Cr/CRu/PR)=(Number of participants whose best overall response was CR/CRu or Cr/CRu/PR)/(Number of participants treated)*100.

2. Percentage of Participants Alive Progression-Free at Year 2 (2-Year PFS Rate) [Randomization to measured PD (up to Year 2)]

   PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. Percentage of participants alive progression-free at Year 2=(Number of participants alive progression free at Year 2)/(Number of participants assessed)*100.

3. Percentage of Participants With a PET-Negative Scan (PET-Negative Rate) [Cycle 6 (21 days/cycle)]

   The percentage of participants with a PET-negative scan=(Number of participants who had a PET-negative scan at Cycle 6)/(Number of participants who had a PET-positive scan at baseline)*100.

4. Percentage of Participants With Complete Response (CR/CRu) and/or Post-Baseline PET-Negative Scan (Concordance Between Response and PET Scan) [Cycle 6 (21 days/cycle)]

   Lesion response was assessed according to International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow. Percentage of participants with CR/CRu and/or PET-negative scan=(Number of participants with complete response and/or PET-negative scan at Cycle 6)/(Number of participants with a PET-positive scan at baseline)*100.

5. Event-Free Survival (EFS) [Randomization to measured PD, start of new therapy, or death from any cause (up to 55 months)]

   EFS is the elapsed time from the date of randomization to the first date of objectively-determined PD, institution of a new anticancer treatment (other than maintenance therapy), or death from any cause. PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. For participants not known to have died as of the data cut-off date, who did not have objectively determined disease progression, and who were not treated with a new anticancer treatment, EFS was censored at the date of the last objectively determined disease-free assessment.

6. Overall Survival (OS) [Baseline to death from any cause (up to 55 months)]

   OS is the elapsed time from the date of study enrollment (baseline) to the date of death from any cause. For participants not known to have died as of the data cutoff date, OS was censored at the last contact date or last date known to be alive, whichever was later.

7. Duration of Complete Response (CR or CRu) [Time of response to PD (up to 55 months)]

   Duration of response (DOR) either CR or CRu: Elapsed time from date CR or CRu criteria met to first objectively-determined PD. For responding participants (pts) who died without PD and pts not known to have died as of data cut-off date, who did not have PD, DOR censored at date of last objective progression-free disease assessment. For responding pts who received subsequent systemic anticancer therapy (other than enzastaurin maintenance therapy) prior to PD, DOR was censored at date of last objective progression-free disease assessment prior to subsequent therapy. CR and CRu defined using International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.

8. Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin) [First dose through 30 days post study treatment discontinuation (up to 56 months)]

   Data presented are the number of participants who experienced at least 1 TEAE, Grade 3 or 4 Common Terminology Criteria for Adverse Events (CTCAE), serious adverse event (SAE), as well as the number of participants who discontinued due to an adverse event (AE) or SAE, who died on therapy, died within 30 days post treatment or within 60 days of first dose. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

9. PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS [Randomization to measured PD or death from any cause (up to 55 months)]]

   Reported is PFS of participants (pts) with high or low biomarker expression levels. PFS: time from randomization to first date of PD/death from any cause. PD assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new/increased lymph node/masses and reappearance of bone marrow infiltrate. For pts who had subsequent anticancer therapy, PFS censored at date of last assessment prior to subsequent therapy. Biomarkers and number of pts censored: EIF4EBP1 Cytoplasm (C) 4,3,7,3; EIF4EBP1 Nucleus (N) 0,2,11,4; EIF4E C 5,2,6,4; EIF4E N 0,0,11,6; HDAC2 N 5,1,5,5; PCREB N 5,3,6,4; PEIF3746 C 4,2,7,4; PEIF3746 N 5,2,6,4; PEIFS209 C 5,2,5,4; PEIFS65 N 7,2,4,4; PEIFT70 C 5,2,6,4; PEIFT70 N 6,4,5,2; P GSK3B C 7,3,4,3; PKCb2 C 4,3,7,3; PS6 C 9,4,1,1; PTEN C 5,2,6,4; PTEN N 3,0,8,6. Correlation of biomarkers with PFS (statistical analyses) reported if high expression groups combined and low expression groups combined each had ≥10 pts.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Participants must:

1. Have a histologically confirmed diagnosis of DLBCL based on the World Health Organization classification (Harris et al. 1999) at the time of original diagnosis. Pathology must be reviewed and confirmed prior to enrollment at the investigational site where the participant is entered. Participants with a prior history of an indolent lymphoma or a histological diagnosis of follicular Grade 3 lymphoma will not be eligible for enrollment.

2. Have received no prior chemotherapy.

3. Have an International Prognostic Index (IPI) score ≥2 at time of original diagnosis.

4. Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology group (ECOG) scale.

5. Have adequate organ function as follows:

• Hepatic: total bilirubin ≤1.5 times the upper limit of normal (x ULN); alanine transaminase (ALT) and aspartate transaminase (AST) ≤1.5 x ULN, (≤5 x ULN, if liver involvement).

• Renal: serum creatinine ≤1.5 x ULN.

• Adequate bone marrow reserve: platelets ≥75 x 10^{9 per Liter (L), absolute neutrophil count (ANC) ≥1.0 x 10}9 per L, unless there is bone marrow involvement.

Exclusion Criteria:

Participants must not:

1. Have received treatment within the last 30 days with a drug (not including enzastaurin) that has not received regulatory approval for any indication at the time of study entry.

2. Are receiving concurrent administration of any other systemic anticancer therapy.

3. Are pregnant or breastfeeding.

4. Are unable to swallow tablets.

5. Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin at least 14 days prior to study enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
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 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Huntsville	Alabama	United States	35805
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Beverly Hills	California	United States	90211
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Greenbrae	California	United States	94904
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Palm Springs	California	United States	92262
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fort Myers	Florida	United States	33916
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Jacksonville	Florida	United States	32256
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chicago	Illinois	United States	60631
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Indianapolis	Indiana	United States	46202
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	South Bend	Indiana	United States	46601
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saint Matthews	Kentucky	United States	40207
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Baltimore	Maryland	United States	21229
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Boston	Massachusetts	United States	02115
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cincinnati	Ohio	United States	45242
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Columbus	Ohio	United States	43235
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Portland	Oregon	United States	97201
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Philadelphia	Pennsylvania	United States	19107
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Willow Grove	Pennsylvania	United States	19090
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chattanooga	Tennessee	United States	37404
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Memphis	Tennessee	United States	38104
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nashville	Tennessee	United States	37203
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Houston	Texas	United States	77030
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	San Antonio	Texas	United States	78229
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Richmond	Virginia	United States	23230
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Everett	Washington	United States	98201
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	La Crosse	Wisconsin	United States	54601

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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 Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00451178
• Other Study ID Numbers: 9824; H6Q-MC-S028
• First Posted: Mar 23, 2007
• Last Update Posted: Jul 21, 2020
• Last Verified: Jul 1, 2020

• Additional relevant MeSH terms: Lymphoma; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Vincristine

Study Results

Participant Flow

Pre-assignment Detail	Study included chemotherapy, maintenance therapy (only R-CHOP and enzastaurin treatment arm) and follow-up post treatment for long-term efficacy.

Arm/Group Title	R-CHOP and Enzastaurin	R-CHOP
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 milligrams (mg) Enzastaurin administered once daily (QD) as four 125-mg tablets, with 1125-mg loading dose [3 tablets, 3 times daily (TID)] on Day 2. R-CHOP included: Rituximab: 375 milligrams per square meter (mg/m^2) intravenous (IV) administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included participants (pts) who had complete response (CR), CR-unconfirmed (CRu) and/or were (positron emission tomography) PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Period Title: Chemotherapy (Up To Six 21-Day Cycles)
STARTED	58	43
Received At Least 1 Dose Study Treatment	57	43
COMPLETED	40	26
NOT COMPLETED	18	17
Period Title: Chemotherapy (Up To Six 21-Day Cycles)
STARTED	40	0
COMPLETED	36	0
NOT COMPLETED	4	0
Period Title: Chemotherapy (Up To Six 21-Day Cycles)
STARTED	36	0
COMPLETED	6	0
NOT COMPLETED	30	0
Period Title: Chemotherapy (Up To Six 21-Day Cycles)
STARTED	6	26
COMPLETED	0	0
NOT COMPLETED	6	26

Baseline Characteristics

Arm/Group Title	R-CHOP and Enzastaurin	R-CHOP	Total
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 mg Enzastaurin administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included pts who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	Total of all reporting groups
Overall Participants	57	43	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.5 (13.55)	63.3 (12.36)	63.4 (12.99)
Sex: Female, Male (Count of Participants)
Female	23 40.4%	21 48.8%	44 44%
Male	34 59.6%	22 51.2%	56 56%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	46 80.7%	39 90.7%	85 85%
African	6 10.5%	3 7%	9 9%
Hispanic	3 5.3%	1 2.3%	4 4%
East Asian	2 3.5%	0 0%	2 2%
West Asian	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	57 100%	43 100%	100 100%
International Prognostic Index (IPI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.88 (0.803)	2.84 (0.843)	2.86 (0.815)

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) Time
Description	PFS time is the elapsed time from the date of randomization to the first date of objectively-determined PD or death from any cause. PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. For participants not known to have died as of the data cut-off date and who did not have objective PD, PFS was censored at the date of the last objective progression-free disease assessment. For participants who received subsequent anticancer therapy (other than enzastaurin maintenance therapy) prior to objectively determined disease progression or death, PFS was censored at the date of the last objective progression-free disease assessment prior to the date of subsequent therapy.
Time Frame	Randomization to measured PD or death from any cause (up to 55 months)

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had at least 1 post-baseline efficacy measurement. A total of 34 and 21 participants were censored in the R-CHOP/Enzastaurin and R-CHOP arms, respectively.

Arm/Group Title	R-CHOP and Enzastaurin	R-CHOP
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 mg Enzastaurin administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included pts who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Measure Participants	56	42
Median (95% Confidence Interval) [months]	36.2	22.6

2. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR and CRu) and Objective Response [CR, CRu, and Partial Response (PR)] (Overall Response Rate)
Description	CR, CRu, and PR were defined using International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow. PR is a 50% decrease in the sum of the products of diameters for up to 6 identified dominant lesions, including splenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. The percentage of participants with complete response (CR/CRu) and objective response (Cr/CRu/PR)=(Number of participants whose best overall response was CR/CRu or Cr/CRu/PR)/(Number of participants treated)*100.
Time Frame	Baseline through long-term follow-up (up to 2 years post last dose)

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had at least 1 post-baseline efficacy measurement.

Arm/Group Title	R-CHOP and Enzastaurin	R-CHOP
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 mg Enzastaurin administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included pts who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Measure Participants	56	42
Complete Response	51.8 90.9%	42.9 99.8%
Objective Response	83.9 147.2%	85.7 199.3%

3. Secondary Outcome

Title	Percentage of Participants Alive Progression-Free at Year 2 (2-Year PFS Rate)
Description	PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. Percentage of participants alive progression-free at Year 2=(Number of participants alive progression free at Year 2)/(Number of participants assessed)*100.
Time Frame	Randomization to measured PD (up to Year 2)

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had at least 1 post-baseline efficacy measurement.

Arm/Group Title	R-CHOP and Enzastaurin	R-CHOP
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 mg Enzastaurin administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included pts who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Measure Participants	56	42
Number (95% Confidence Interval) [percentage of participants]	59 103.5%	49 114%

4. Secondary Outcome

Title	Percentage of Participants With a PET-Negative Scan (PET-Negative Rate)
Description	The percentage of participants with a PET-negative scan=(Number of participants who had a PET-negative scan at Cycle 6)/(Number of participants who had a PET-positive scan at baseline)*100.
Time Frame	Cycle 6 (21 days/cycle)

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had a PET-positive scan at baseline.

Arm/Group Title	R-CHOP and Enzastaurin	R-CHOP
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 mg Enzastaurin administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included pts who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Measure Participants	56	39
Number (95% Confidence Interval) [percentage of participants]	44.6 78.2%	41.0 95.3%

5. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR/CRu) and/or Post-Baseline PET-Negative Scan (Concordance Between Response and PET Scan)
Description	Lesion response was assessed according to International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow. Percentage of participants with CR/CRu and/or PET-negative scan=(Number of participants with complete response and/or PET-negative scan at Cycle 6)/(Number of participants with a PET-positive scan at baseline)*100.
Time Frame	Cycle 6 (21 days/cycle)

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen, who had a PET-positive scan at baseline.

Arm/Group Title	R-CHOP and Enzastaurin	R-CHOP
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 mg Enzastaurin administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included pts who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Measure Participants	56	39
CR/CRu and PET-Negative Post-Baseline	26.8 47%	25.6 59.5%
CR/CRu or PET-Negative Post-Baseline	53.6 94%	43.6 101.4%

6. Secondary Outcome

Title	Event-Free Survival (EFS)
Description	EFS is the elapsed time from the date of randomization to the first date of objectively-determined PD, institution of a new anticancer treatment (other than maintenance therapy), or death from any cause. PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. For participants not known to have died as of the data cut-off date, who did not have objectively determined disease progression, and who were not treated with a new anticancer treatment, EFS was censored at the date of the last objectively determined disease-free assessment.
Time Frame	Randomization to measured PD, start of new therapy, or death from any cause (up to 55 months)

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had at least 1 post-baseline efficacy measurement. A total of 31 and 20 participants were censored in the R-CHOP/Enzastaurin and R-CHOP arms, respectively.

Arm/Group Title	R-CHOP and Enzastaurin	R-CHOP
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 mg Enzastaurin administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included pts who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Measure Participants	56	42
Median (95% Confidence Interval) [months]	36.2	22.6

7. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is the elapsed time from the date of study enrollment (baseline) to the date of death from any cause. For participants not known to have died as of the data cutoff date, OS was censored at the last contact date or last date known to be alive, whichever was later.
Time Frame	Baseline to death from any cause (up to 55 months)

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who had at least 1 post-baseline efficacy measurement. A total of 42 and 28 participants were censored in the R-CHOP/Enzastaurin and R-CHOP arms, respectively.

Arm/Group Title	R-CHOP and Enzastaurin	R-CHOP
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 mg Enzastaurin administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included pts who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Measure Participants	56	42
Median (95% Confidence Interval) [months]	NA	NA

8. Secondary Outcome

Title	Duration of Complete Response (CR or CRu)
Description	Duration of response (DOR) either CR or CRu: Elapsed time from date CR or CRu criteria met to first objectively-determined PD. For responding participants (pts) who died without PD and pts not known to have died as of data cut-off date, who did not have PD, DOR censored at date of last objective progression-free disease assessment. For responding pts who received subsequent systemic anticancer therapy (other than enzastaurin maintenance therapy) prior to PD, DOR was censored at date of last objective progression-free disease assessment prior to subsequent therapy. CR and CRu defined using International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.
Time Frame	Time of response to PD (up to 55 months)

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen who achieved CR or CRu. A total of 22 and 9 participants were censored in the R-CHOP/Enzastaurin and R-CHOP arms, respectively.

Arm/Group Title	R-CHOP and Enzastaurin	R-CHOP
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 mg Enzastaurin administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included pts who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Measure Participants	27	11
Median (95% Confidence Interval) [days]	NA	NA

9. Secondary Outcome

Title	Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin)
Description	Data presented are the number of participants who experienced at least 1 TEAE, Grade 3 or 4 Common Terminology Criteria for Adverse Events (CTCAE), serious adverse event (SAE), as well as the number of participants who discontinued due to an adverse event (AE) or SAE, who died on therapy, died within 30 days post treatment or within 60 days of first dose. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame	First dose through 30 days post study treatment discontinuation (up to 56 months)

Outcome Measure Data

Analysis Population Description

Safety Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen.

Arm/Group Title	R-CHOP and Enzastaurin	R-CHOP
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 mg Enzastaurin administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included pts who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Measure Participants	57	43
At Least 1 TEAE	56 98.2%	43 100%
At Least 1 Grade 3/4 CTCAE	50 87.7%	30 69.8%
At Least 1 SAE	35 61.4%	18 41.9%
Discontinued due to AE	10 17.5%	6 14%
Discontinued due to SAE	4 7%	3 7%
Died on Therapy (all causes)	5 8.8%	3 7%
Died within 30 days post treatment discontinuation	6 10.5%	3 7%
Died within 60 days of first dose	3 5.3%	2 4.7%

10. Secondary Outcome

Title	PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Description	Reported is PFS of participants (pts) with high or low biomarker expression levels. PFS: time from randomization to first date of PD/death from any cause. PD assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new/increased lymph node/masses and reappearance of bone marrow infiltrate. For pts who had subsequent anticancer therapy, PFS censored at date of last assessment prior to subsequent therapy. Biomarkers and number of pts censored: EIF4EBP1 Cytoplasm (C) 4,3,7,3; EIF4EBP1 Nucleus (N) 0,2,11,4; EIF4E C 5,2,6,4; EIF4E N 0,0,11,6; HDAC2 N 5,1,5,5; PCREB N 5,3,6,4; PEIF3746 C 4,2,7,4; PEIF3746 N 5,2,6,4; PEIFS209 C 5,2,5,4; PEIFS65 N 7,2,4,4; PEIFT70 C 5,2,6,4; PEIFT70 N 6,4,5,2; P GSK3B C 7,3,4,3; PKCb2 C 4,3,7,3; PS6 C 9,4,1,1; PTEN C 5,2,6,4; PTEN N 3,0,8,6. Correlation of biomarkers with PFS (statistical analyses) reported if high expression groups combined and low expression groups combined each had ≥10 pts.
Time Frame	Randomization to measured PD or death from any cause (up to 55 months)]

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen, who had at least 1 post-baseline efficacy measurement and had a reported value for the biomarker measure of interest.

Arm/Group Title	High Biomarker Expression (R-CHOP and Enzastaurin)	High Biomarker Expression (R-CHOP)	Low Biomarker Expression (R-CHOP and Enzastaurin)	Low Biomarker Expression (R-CHOP)
Arm/Group Description	Participants with high relative biomarker expression levels who were randomized to R-CHOP and Enzastaurin chemotherapy, up to 6 cycles, 21 days/cycle. For each cycle, R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Enzastaurin: 500 mg administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. Only R-CHOP and Enzastaurin participants eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included participants who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if participants had PR and/or were PET-positive/equivocal, or participants who discontinued therapy before 6 cycles otherwise met response criteria.	Participants with high relative biomarker expression levels who were randomized to R-CHOP chemotherapy, up to 6 cycles, 21 days/cycle. For each cycle, R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	Participants with low relative biomarker expression levels who were randomized to R-CHOP and Enzastaurin chemotherapy, up to 6 cycles, 21 days/cycle. For each cycle, R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Enzastaurin: 500 mg administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. Only R-CHOP and Enzastaurin participants eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included participants who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if participants had PR and/or were PET-positive/equivocal, or participants who discontinued therapy before 6 cycles otherwise met response criteria.	Participants with low relative biomarker expression levels who were randomized to R-CHOP chemotherapy, up to 6 cycles, 21 days/cycle. For each cycle, R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Measure Participants	14	10	18	11
Marker: EIF4EBP1 Cytoplasm	NA	9.49	27.96	32.30
Marker: EIF4EBP1 Nucleus	NA	NA	10.55
Marker: EIF4E Cytoplasm	NA	21.42	27.96	NA
Marker: EIF4E Nucleus	4.50	NA	32.30
Marker: HDAC2 Nucleus	27.96	10.55	NA	NA
Marker: PCREB Nucleus	24.10	10.55	NA	NA
Marker: PEIF3746 Cytoplasm	27.96	20.90	NA	NA
Marker: PEIF3746 Nucleus	NA	NA	NA	32.30
Marker: PEIFS209 Cytoplasm	NA	9.20	27.96	NA
Marker: PEIFS65 Nucleus	NA	NA	27.96	32.30
Marker: PEIFT70 Cytoplasm	NA	NA	27.96	10.55
Marker: PEIFT70 Nucleus	NA	32.30	27.96	NA
Marker: P GSK3B Cytoplasm	27.96	21.42	NA	9.49
Marker: PKCb2 Cytoplasm	27.96	10.55	NA	20.90
Marker: PS6 Cytoplasm	NA	10.02	16.57	NA
Marker: PTEN Cytoplasm	27.96	21.42	NA	9.49
Marker: PTEN Nucleus	27.96	6.34	NA	32.30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker EIF4EBP1 Cytoplasm with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.989
	Confidence Interval	(2-Sided) 95%; 0.223 to 4.393
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of EIF4EBP1 Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of EIF4EBP1 Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP and Enzastaurin), Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker EIF4E Cytoplasm with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.071
	Confidence Interval	(2-Sided) 95%; 0.316 to 3.628
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of EIF4E Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of EIF4E Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP and Enzastaurin), Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker HDAC2 Nucleus with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.658
	Confidence Interval	(2-Sided) 95%; 0.454 to 6.053
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of HDAC2 Nucleus [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of HDAC2 Nucleus [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP and Enzastaurin), Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker PCREB Nucleus with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	4.082
	Confidence Interval	(2-Sided) 95%; 0.455 to 36.628
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of PCREB Nucleus [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of PCREB Nucleus [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP and Enzastaurin), Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker PEIF3746 Cytoplasm with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.636
	Confidence Interval	(2-Sided) 95%; 0.180 to 2.253
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of PEIF3746 Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of PEIF3746 Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP and Enzastaurin), Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker PEIF3746 Nucleus with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.362
	Confidence Interval	(2-Sided) 95%; 0.083 to 1.576
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of PEIF3746 Nucleus [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of PEIF3746 Nucleus [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP and Enzastaurin), Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker PEIFS209 Cytoplasm with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.522
	Confidence Interval	(2-Sided) 95%; 0.473 to 4.901
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of PEIFS209 Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of PEIFS209 Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP and Enzastaurin), Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker PEIFS65 Nucleus with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.908
	Confidence Interval	(2-Sided) 95%; 0.223 to 3.699
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of PEIFS65 Nucleus [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of PEIFS65 Nucleus [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP and Enzastaurin), Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker PEIFT70 Nucleus with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.843
	Confidence Interval	(2-Sided) 95%; 0.432 to 7.867
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of PEIFT70 Nucleus [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of PEIFT70 Nucleus [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP and Enzastaurin), Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker P GSK3B Cytoplasm with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.926
	Confidence Interval	(2-Sided) 95%; 0.276 to 3.109
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of P GSK3B Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of P GSK3B Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP and Enzastaurin), Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker PKCb2 Cytoplasm with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.985
	Confidence Interval	(2-Sided) 95%; 0.320 to 3.033
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of PKCb2 Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of PKCb2 Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	R-CHOP and Enzastaurin, R-CHOP, Low Biomarker Expression (R-CHOP and Enzastaurin), Low Biomarker Expression (R-CHOP)
	Comments	The correlation of biomarker PTEN Cytoplasm with PFS.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.817
	Confidence Interval	(2-Sided) 95%; 0.242 to 2.758
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio comparing PFS of participants with a high expression of PTEN Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined] versus participants with a low expression of PTEN Cytoplasm [(R-CHOP and Enzastaurin) and (R-CHOP) combined].

Adverse Events

Arm/Group Title	R-CHOP and Enzastaurin		R-CHOP
Arm/Group Description	Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP and 500 mg Enzastaurin administered QD as four 125-mg tablets, with 1125-mg loading dose (3 tablets, TID) on Day 2. R-CHOP included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 Only this arm eligible for maintenance therapy (500 mg enzastaurin, QD up to 3 years). This included pts who had CR, CRu and/or were PET-negative. Maintenance therapy allowed, at investigator's discretion, if pts had PR and/or were PET-positive/equivocal, or pts who discontinued therapy before 6 cycles otherwise met response criteria.		Chemotherapy for up to 6 cycles, 21 days/cycle, with R-CHOP. For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m^2 IV administration on Day 1 Doxorubicin: 50 mg/m^2 IV administration on Day 1 Vincristine: 1.4 mg/m^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
All Cause Mortality
	R-CHOP and Enzastaurin		R-CHOP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	R-CHOP and Enzastaurin		R-CHOP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/57 (61.4%)		18/43 (41.9%)
Blood and lymphatic system disorders
Anaemia	4/57 (7%)	4	1/43 (2.3%)	1
Febrile neutropenia	9/57 (15.8%)	12	3/43 (7%)	5
Leukopenia	0/57 (0%)	0	1/43 (2.3%)	1
Neutropenia	2/57 (3.5%)	2	3/43 (7%)	4
Thrombocytopenia	1/57 (1.8%)	1	2/43 (4.7%)	2
Cardiac disorders
Angina unstable	0/57 (0%)	0	1/43 (2.3%)	1
Atrial fibrillation	1/57 (1.8%)	1	2/43 (4.7%)	3
Atrioventricular block	1/57 (1.8%)	1	1/43 (2.3%)	1
Cardio-respiratory arrest	1/57 (1.8%)	1	0/43 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/57 (3.5%)	2	0/43 (0%)	0
Anal fistula	1/57 (1.8%)	1	0/43 (0%)	0
Constipation	2/57 (3.5%)	2	0/43 (0%)	0
Diarrhoea	1/57 (1.8%)	1	0/43 (0%)	0
Diverticular perforation	1/57 (1.8%)	1	0/43 (0%)	0
Dysphagia	1/57 (1.8%)	1	0/43 (0%)	0
Gastrointestinal haemorrhage	2/57 (3.5%)	2	0/43 (0%)	0
Nausea	1/57 (1.8%)	1	1/43 (2.3%)	1
Oesophageal disorder	0/57 (0%)	0	1/43 (2.3%)	1
Oesophageal ulcer haemorrhage	1/57 (1.8%)	1	0/43 (0%)	0
Small intestinal obstruction	0/57 (0%)	0	1/43 (2.3%)	1
Vomiting	0/57 (0%)	0	1/43 (2.3%)	1
General disorders
Asthenia	1/57 (1.8%)	1	0/43 (0%)	0
Fatigue	1/57 (1.8%)	1	1/43 (2.3%)	1
Multi-organ failure	1/57 (1.8%)	1	0/43 (0%)	0
Pain	1/57 (1.8%)	1	0/43 (0%)	0
Pyrexia	3/57 (5.3%)	3	4/43 (9.3%)	4
Immune system disorders
Hypersensitivity	0/57 (0%)	0	1/43 (2.3%)	1
Infections and infestations
Alpha haemolytic streptococcal infection	1/57 (1.8%)	1	0/43 (0%)	0
Bacteraemia	2/57 (3.5%)	2	1/43 (2.3%)	1
Cellulitis	1/57 (1.8%)	1	0/43 (0%)	0
Cellulitis orbital	1/57 (1.8%)	1	0/43 (0%)	0
Infection	1/57 (1.8%)	1	1/43 (2.3%)	1
Neutropenic sepsis	1/57 (1.8%)	2	0/43 (0%)	0
Pneumonia	5/57 (8.8%)	5	2/43 (4.7%)	2
Pneumonia streptococcal	1/57 (1.8%)	1	0/43 (0%)	0
Sepsis	2/57 (3.5%)	2	4/43 (9.3%)	5
Septic shock	1/57 (1.8%)	1	1/43 (2.3%)	1
Tooth abscess	1/57 (1.8%)	1	0/43 (0%)	0
Urinary tract infection	2/57 (3.5%)	2	2/43 (4.7%)	2
Urosepsis	0/57 (0%)	0	1/43 (2.3%)	1
Viral upper respiratory tract infection	1/57 (1.8%)	1	0/43 (0%)	0
Injury, poisoning and procedural complications
Fall	1/57 (1.8%)	1	0/43 (0%)	0
Femoral neck fracture	1/57 (1.8%)	1	0/43 (0%)	0
Fibula fracture	1/57 (1.8%)	1	0/43 (0%)	0
Tibia fracture	1/57 (1.8%)	1	0/43 (0%)	0
Investigations
Alanine aminotransferase increased	0/57 (0%)	0	1/43 (2.3%)	1
Aspartate aminotransferase increased	0/57 (0%)	0	1/43 (2.3%)	1
Blood alkaline phosphatase increased	0/57 (0%)	0	1/43 (2.3%)	1
Haemoglobin decreased	1/57 (1.8%)	1	1/43 (2.3%)	1
Weight decreased	1/57 (1.8%)	1	0/43 (0%)	0
Metabolism and nutrition disorders
Dehydration	2/57 (3.5%)	2	0/43 (0%)	0
Hyperkalaemia	1/57 (1.8%)	1	0/43 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	1/57 (1.8%)	1	0/43 (0%)	0
Pathological fracture	1/57 (1.8%)	1	0/43 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges	1/57 (1.8%)	1	0/43 (0%)	0
Thyroid cancer	1/57 (1.8%)	1	0/43 (0%)	0
Nervous system disorders
Hypoaesthesia	1/57 (1.8%)	1	0/43 (0%)	0
Neuropathy peripheral	1/57 (1.8%)	1	0/43 (0%)	0
Syncope	2/57 (3.5%)	3	0/43 (0%)	0
Psychiatric disorders
Depression	0/57 (0%)	0	1/43 (2.3%)	1
Mental status changes	1/57 (1.8%)	1	0/43 (0%)	0
Renal and urinary disorders
Renal failure	0/57 (0%)	0	1/43 (2.3%)	1
Renal failure acute	1/57 (1.8%)	1	0/43 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/57 (1.8%)	1	0/43 (0%)	0
Epistaxis	1/57 (1.8%)	1	0/43 (0%)	0
Pleural effusion	1/57 (1.8%)	1	0/43 (0%)	0
Pulmonary embolism	2/57 (3.5%)	2	1/43 (2.3%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/57 (0%)	0	1/43 (2.3%)	1
Vascular disorders
Deep vein thrombosis	2/57 (3.5%)	2	1/43 (2.3%)	1
Hypertension	1/57 (1.8%)	1	0/43 (0%)	0
Hypotension	3/57 (5.3%)	3	0/43 (0%)	0
Orthostatic hypotension	0/57 (0%)	0	1/43 (2.3%)	1
Other (Not Including Serious) Adverse Events
	R-CHOP and Enzastaurin		R-CHOP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/57 (98.2%)		43/43 (100%)
Blood and lymphatic system disorders
Anaemia	22/57 (38.6%)	26	14/43 (32.6%)	16
Leukopenia	16/57 (28.1%)	40	14/43 (32.6%)	33
Lymphopenia	4/57 (7%)	8	0/43 (0%)	0
Neutropenia	33/57 (57.9%)	77	26/43 (60.5%)	59
Thrombocytopenia	16/57 (28.1%)	38	18/43 (41.9%)	38
Cardiac disorders
Palpitations	3/57 (5.3%)	3	2/43 (4.7%)	2
Eye disorders
Lacrimation increased	6/57 (10.5%)	8	4/43 (9.3%)	6
Periorbital oedema	3/57 (5.3%)	10	0/43 (0%)	0
Vision blurred	5/57 (8.8%)	8	4/43 (9.3%)	5
Gastrointestinal disorders
Abdominal pain	7/57 (12.3%)	8	4/43 (9.3%)	4
Abdominal pain upper	3/57 (5.3%)	4	0/43 (0%)	0
Constipation	22/57 (38.6%)	22	18/43 (41.9%)	25
Diarrhoea	27/57 (47.4%)	35	15/43 (34.9%)	18
Dyspepsia	4/57 (7%)	4	1/43 (2.3%)	1
Gastritis	3/57 (5.3%)	3	0/43 (0%)	0
Gastrooesophageal reflux disease	2/57 (3.5%)	2	4/43 (9.3%)	4
Nausea	29/57 (50.9%)	46	19/43 (44.2%)	28
Stomatitis	19/57 (33.3%)	28	10/43 (23.3%)	13
Vomiting	11/57 (19.3%)	15	3/43 (7%)	3
General disorders
Asthenia	9/57 (15.8%)	11	5/43 (11.6%)	6
Chills	6/57 (10.5%)	6	3/43 (7%)	5
Fatigue	30/57 (52.6%)	37	29/43 (67.4%)	40
Oedema	3/57 (5.3%)	3	1/43 (2.3%)	1
Oedema peripheral	18/57 (31.6%)	30	10/43 (23.3%)	10
Pain	5/57 (8.8%)	5	3/43 (7%)	3
Pyrexia	13/57 (22.8%)	18	7/43 (16.3%)	7
Infections and infestations
Candidiasis	4/57 (7%)	5	2/43 (4.7%)	2
Oral candidiasis	3/57 (5.3%)	3	1/43 (2.3%)	1
Pneumonia	3/57 (5.3%)	3	0/43 (0%)	0
Staphylococcal infection	3/57 (5.3%)	3	0/43 (0%)	0
Upper respiratory tract infection	6/57 (10.5%)	7	0/43 (0%)	0
Urinary tract infection	8/57 (14%)	11	1/43 (2.3%)	2
Vulvovaginal mycotic infection	2/23 (8.7%)	2	0/21 (0%)	0
Investigations
Alanine aminotransferase increased	3/57 (5.3%)	4	2/43 (4.7%)	2
Blood creatinine increased	4/57 (7%)	7	1/43 (2.3%)	1
Haemoglobin decreased	5/57 (8.8%)	5	0/43 (0%)	0
Neutrophil count decreased	3/57 (5.3%)	3	0/43 (0%)	0
Platelet count decreased	3/57 (5.3%)	4	0/43 (0%)	0
Weight decreased	9/57 (15.8%)	9	3/43 (7%)	3
Weight increased	6/57 (10.5%)	6	1/43 (2.3%)	1
White blood cell count decreased	3/57 (5.3%)	6	1/43 (2.3%)	1
Metabolism and nutrition disorders
Decreased appetite	14/57 (24.6%)	17	5/43 (11.6%)	5
Dehydration	9/57 (15.8%)	14	6/43 (14%)	7
Hyperglycaemia	3/57 (5.3%)	4	4/43 (9.3%)	4
Hypoalbuminaemia	3/57 (5.3%)	4	1/43 (2.3%)	1
Hypocalcaemia	3/57 (5.3%)	3	1/43 (2.3%)	1
Hypokalaemia	5/57 (8.8%)	6	1/43 (2.3%)	1
Hypomagnesaemia	3/57 (5.3%)	3	2/43 (4.7%)	2
Hyponatraemia	3/57 (5.3%)	3	3/43 (7%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	10/57 (17.5%)	13	5/43 (11.6%)	7
Back pain	10/57 (17.5%)	12	4/43 (9.3%)	5
Bone pain	8/57 (14%)	8	4/43 (9.3%)	5
Muscle spasms	3/57 (5.3%)	4	0/43 (0%)	0
Muscular weakness	2/57 (3.5%)	2	3/43 (7%)	3
Musculoskeletal pain	3/57 (5.3%)	3	1/43 (2.3%)	1
Myalgia	4/57 (7%)	5	3/43 (7%)	7
Pain in extremity	11/57 (19.3%)	12	0/43 (0%)	0
Pain in jaw	3/57 (5.3%)	3	2/43 (4.7%)	2
Nervous system disorders
Dizziness	17/57 (29.8%)	20	5/43 (11.6%)	6
Dysgeusia	10/57 (17.5%)	11	4/43 (9.3%)	4
Headache	9/57 (15.8%)	12	3/43 (7%)	4
Memory impairment	4/57 (7%)	4	1/43 (2.3%)	1
Neuropathy peripheral	18/57 (31.6%)	23	8/43 (18.6%)	9
Paraesthesia	4/57 (7%)	4	1/43 (2.3%)	1
Peripheral sensory neuropathy	8/57 (14%)	8	6/43 (14%)	6
Psychiatric disorders
Anxiety	3/57 (5.3%)	3	2/43 (4.7%)	2
Depression	3/57 (5.3%)	3	2/43 (4.7%)	2
Insomnia	11/57 (19.3%)	11	9/43 (20.9%)	10
Renal and urinary disorders
Chromaturia	5/57 (8.8%)	5	0/43 (0%)	0
Nocturia	4/57 (7%)	4	1/43 (2.3%)	1
Pollakiuria	3/57 (5.3%)	3	1/43 (2.3%)	1
Urinary incontinence	3/57 (5.3%)	3	0/43 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	10/57 (17.5%)	12	8/43 (18.6%)	8
Dyspnoea	10/57 (17.5%)	11	11/43 (25.6%)	13
Hiccups	4/57 (7%)	5	1/43 (2.3%)	1
Nasal congestion	3/57 (5.3%)	3	3/43 (7%)	3
Oropharyngeal pain	9/57 (15.8%)	9	5/43 (11.6%)	5
Skin and subcutaneous tissue disorders
Alopecia	26/57 (45.6%)	26	17/43 (39.5%)	17
Dry skin	3/57 (5.3%)	4	0/43 (0%)	0
Night sweats	4/57 (7%)	4	1/43 (2.3%)	1
Rash	9/57 (15.8%)	10	5/43 (11.6%)	5
Skin hyperpigmentation	5/57 (8.8%)	5	0/43 (0%)	0
Vascular disorders
Deep vein thrombosis	2/57 (3.5%)	2	4/43 (9.3%)	4
Hypertension	1/57 (1.8%)	2	3/43 (7%)	3
Hypotension	6/57 (10.5%)	6	4/43 (9.3%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.