Trial Outcomes & Findings for A Study of Participants With Lymphoma Who Take R-CHOP and Enzastaurin Compared to Participants Who Take R-CHOP Only (NCT NCT00451178)
NCT ID: NCT00451178
Last Updated: 2020-07-21
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
101 participants
Primary outcome timeframe
Randomization to measured PD or death from any cause (up to 55 months)
Results posted on
2020-07-21
Participant Flow
Study included chemotherapy, maintenance therapy (only R-CHOP and enzastaurin treatment arm) and follow-up post treatment for long-term efficacy.
Participant milestones
| Measure |
R-CHOP and Enzastaurin
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.
|
R-CHOP
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
|
|---|---|---|
|
Chemotherapy (Up To Six 21-Day Cycles)
STARTED
|
58
|
43
|
|
Chemotherapy (Up To Six 21-Day Cycles)
Received At Least 1 Dose Study Treatment
|
57
|
43
|
|
Chemotherapy (Up To Six 21-Day Cycles)
COMPLETED
|
40
|
26
|
|
Chemotherapy (Up To Six 21-Day Cycles)
NOT COMPLETED
|
18
|
17
|
|
Prior to Maintenance Therapy
STARTED
|
40
|
0
|
|
Prior to Maintenance Therapy
COMPLETED
|
36
|
0
|
|
Prior to Maintenance Therapy
NOT COMPLETED
|
4
|
0
|
|
Maintenance Therapy (up to 3 Years)
STARTED
|
36
|
0
|
|
Maintenance Therapy (up to 3 Years)
COMPLETED
|
6
|
0
|
|
Maintenance Therapy (up to 3 Years)
NOT COMPLETED
|
30
|
0
|
|
Long-Term Follow-Up (Up to 2 Years)
STARTED
|
6
|
26
|
|
Long-Term Follow-Up (Up to 2 Years)
COMPLETED
|
0
|
0
|
|
Long-Term Follow-Up (Up to 2 Years)
NOT COMPLETED
|
6
|
26
|
Reasons for withdrawal
| Measure |
R-CHOP and Enzastaurin
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.
|
R-CHOP
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
|
|---|---|---|
|
Chemotherapy (Up To Six 21-Day Cycles)
Adverse Event
|
6
|
6
|
|
Chemotherapy (Up To Six 21-Day Cycles)
Withdrawal by Subject
|
4
|
3
|
|
Chemotherapy (Up To Six 21-Day Cycles)
Protocol Violation
|
2
|
1
|
|
Chemotherapy (Up To Six 21-Day Cycles)
Physician Decision
|
1
|
2
|
|
Chemotherapy (Up To Six 21-Day Cycles)
Death
|
4
|
3
|
|
Chemotherapy (Up To Six 21-Day Cycles)
Progressive Disease (PD)
|
1
|
2
|
|
Prior to Maintenance Therapy
Physician Decision
|
2
|
0
|
|
Prior to Maintenance Therapy
PD
|
2
|
0
|
|
Maintenance Therapy (up to 3 Years)
Adverse Event
|
4
|
0
|
|
Maintenance Therapy (up to 3 Years)
Withdrawal by Subject
|
5
|
0
|
|
Maintenance Therapy (up to 3 Years)
Physician Decision
|
1
|
0
|
|
Maintenance Therapy (up to 3 Years)
Death
|
1
|
0
|
|
Maintenance Therapy (up to 3 Years)
PD
|
10
|
0
|
|
Maintenance Therapy (up to 3 Years)
Continuing Maintenance
|
9
|
0
|
|
Long-Term Follow-Up (Up to 2 Years)
Continuing Follow-Up
|
6
|
26
|
Baseline Characteristics
A Study of Participants With Lymphoma Who Take R-CHOP and Enzastaurin Compared to Participants Who Take R-CHOP Only
Baseline characteristics by cohort
| Measure |
R-CHOP and Enzastaurin
n=57 Participants
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.
|
R-CHOP
n=43 Participants
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
n=100 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.5 years
STANDARD_DEVIATION 13.55 • n=5 Participants
|
63.3 years
STANDARD_DEVIATION 12.36 • n=7 Participants
|
63.4 years
STANDARD_DEVIATION 12.99 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
46 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
85 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
West Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
57 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
International Prognostic Index (IPI)
|
2.88 units on a scale
STANDARD_DEVIATION 0.803 • n=5 Participants
|
2.84 units on a scale
STANDARD_DEVIATION 0.843 • n=7 Participants
|
2.86 units on a scale
STANDARD_DEVIATION 0.815 • n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization to measured PD or death from any cause (up to 55 months)Population: 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.
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.
Outcome measures
| Measure |
R-CHOP and Enzastaurin
n=56 Participants
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.
|
R-CHOP
n=42 Participants
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
|
Low Biomarker Expression (R-CHOP and Enzastaurin)
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.
|
Low Biomarker Expression (R-CHOP)
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
|
|---|---|---|---|---|
|
Progression-Free Survival (PFS) Time
|
36.2 months
Interval 20.2 to
The upper 95% confidence interval was not estimable due to the high rate of censoring.
|
22.6 months
Interval 8.9 to
The upper 95% confidence interval was not estimable due to the high rate of censoring.
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through long-term follow-up (up to 2 years post last dose)Population: 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.
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.
Outcome measures
| Measure |
R-CHOP and Enzastaurin
n=56 Participants
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.
|
R-CHOP
n=42 Participants
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
|
Low Biomarker Expression (R-CHOP and Enzastaurin)
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.
|
Low Biomarker Expression (R-CHOP)
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
|
|---|---|---|---|---|
|
Percentage of Participants With Complete Response (CR and CRu) and Objective Response [CR, CRu, and Partial Response (PR)] (Overall Response Rate)
Complete Response
|
51.8 percentage of participants
Interval 38.0 to 65.3
|
42.9 percentage of participants
Interval 27.7 to 59.0
|
—
|
—
|
|
Percentage of Participants With Complete Response (CR and CRu) and Objective Response [CR, CRu, and Partial Response (PR)] (Overall Response Rate)
Objective Response
|
83.9 percentage of participants
Interval 71.7 to 92.4
|
85.7 percentage of participants
Interval 71.5 to 94.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Randomization to measured PD (up to Year 2)Population: 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.
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.
Outcome measures
| Measure |
R-CHOP and Enzastaurin
n=56 Participants
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.
|
R-CHOP
n=42 Participants
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
|
Low Biomarker Expression (R-CHOP and Enzastaurin)
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.
|
Low Biomarker Expression (R-CHOP)
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
|
|---|---|---|---|---|
|
Percentage of Participants Alive Progression-Free at Year 2 (2-Year PFS Rate)
|
59 percentage of participants
Interval 45.0 to 73.0
|
49 percentage of participants
Interval 32.0 to 66.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 6 (21 days/cycle)Population: 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.
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.
Outcome measures
| Measure |
R-CHOP and Enzastaurin
n=56 Participants
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.
|
R-CHOP
n=39 Participants
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
|
Low Biomarker Expression (R-CHOP and Enzastaurin)
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.
|
Low Biomarker Expression (R-CHOP)
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
|
|---|---|---|---|---|
|
Percentage of Participants With a PET-Negative Scan (PET-Negative Rate)
|
44.6 percentage of participants
Interval 31.3 to 58.5
|
41.0 percentage of participants
Interval 25.6 to 57.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 6 (21 days/cycle)Population: 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.
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.
Outcome measures
| Measure |
R-CHOP and Enzastaurin
n=56 Participants
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.
|
R-CHOP
n=39 Participants
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
|
Low Biomarker Expression (R-CHOP and Enzastaurin)
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.
|
Low Biomarker Expression (R-CHOP)
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
|
|---|---|---|---|---|
|
Percentage of Participants With Complete Response (CR/CRu) and/or Post-Baseline PET-Negative Scan (Concordance Between Response and PET Scan)
CR/CRu and PET-Negative Post-Baseline
|
26.8 percentage of participants
|
25.6 percentage of participants
|
—
|
—
|
|
Percentage of Participants With Complete Response (CR/CRu) and/or Post-Baseline PET-Negative Scan (Concordance Between Response and PET Scan)
CR/CRu or PET-Negative Post-Baseline
|
53.6 percentage of participants
|
43.6 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Randomization to measured PD, start of new therapy, or death from any cause (up to 55 months)Population: 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.
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.
Outcome measures
| Measure |
R-CHOP and Enzastaurin
n=56 Participants
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.
|
R-CHOP
n=42 Participants
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
|
Low Biomarker Expression (R-CHOP and Enzastaurin)
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.
|
Low Biomarker Expression (R-CHOP)
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
|
|---|---|---|---|---|
|
Event-Free Survival (EFS)
|
36.2 months
Interval 14.6 to
The upper 95% confidence interval was not estimable due to the high rate of censoring.
|
22.6 months
Interval 8.9 to
The upper 95% confidence interval was not estimable due to the high rate of censoring.
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to death from any cause (up to 55 months)Population: 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.
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.
Outcome measures
| Measure |
R-CHOP and Enzastaurin
n=56 Participants
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.
|
R-CHOP
n=42 Participants
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
|
Low Biomarker Expression (R-CHOP and Enzastaurin)
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.
|
Low Biomarker Expression (R-CHOP)
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
|
|---|---|---|---|---|
|
Overall Survival (OS)
|
NA months
The median and 95% confidence interval were not estimable due to the high rate of censoring.
|
NA months
Interval 32.3 to
The median and upper 95% confidence interval were not estimable due to the high rate of censoring.
|
—
|
—
|
SECONDARY outcome
Timeframe: Time of response to PD (up to 55 months)Population: 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.
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.
Outcome measures
| Measure |
R-CHOP and Enzastaurin
n=27 Participants
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.
|
R-CHOP
n=11 Participants
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
|
Low Biomarker Expression (R-CHOP and Enzastaurin)
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.
|
Low Biomarker Expression (R-CHOP)
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
|
|---|---|---|---|---|
|
Duration of Complete Response (CR or CRu)
|
NA days
Interval 813.0 to
The median and upper 95% confidence interval were not estimable due to the high rate of censoring.
|
NA days
Interval 1053.0 to
The median and upper 95% confidence interval were not estimable due to the high rate of censoring.
|
—
|
—
|
SECONDARY outcome
Timeframe: First dose through 30 days post study treatment discontinuation (up to 56 months)Population: Safety Population: Randomized participants who received at least 1 dose of enzastaurin or any drug in the R-CHOP regimen.
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.
Outcome measures
| Measure |
R-CHOP and Enzastaurin
n=57 Participants
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.
|
R-CHOP
n=43 Participants
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
|
Low Biomarker Expression (R-CHOP and Enzastaurin)
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.
|
Low Biomarker Expression (R-CHOP)
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
|
|---|---|---|---|---|
|
Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin)
At Least 1 TEAE
|
56 Participants
|
43 Participants
|
—
|
—
|
|
Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin)
At Least 1 Grade 3/4 CTCAE
|
50 Participants
|
30 Participants
|
—
|
—
|
|
Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin)
At Least 1 SAE
|
35 Participants
|
18 Participants
|
—
|
—
|
|
Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin)
Discontinued due to AE
|
10 Participants
|
6 Participants
|
—
|
—
|
|
Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin)
Discontinued due to SAE
|
4 Participants
|
3 Participants
|
—
|
—
|
|
Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin)
Died on Therapy (all causes)
|
5 Participants
|
3 Participants
|
—
|
—
|
|
Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin)
Died within 30 days post treatment discontinuation
|
6 Participants
|
3 Participants
|
—
|
—
|
|
Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin)
Died within 60 days of first dose
|
3 Participants
|
2 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Randomization to measured PD or death from any cause (up to 55 months)]Population: 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.
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.
Outcome measures
| Measure |
R-CHOP and Enzastaurin
n=14 Participants
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.
|
R-CHOP
n=10 Participants
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
|
Low Biomarker Expression (R-CHOP and Enzastaurin)
n=18 Participants
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.
|
Low Biomarker Expression (R-CHOP)
n=11 Participants
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
|
|---|---|---|---|---|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: EIF4EBP1 Cytoplasm
|
NA months
Interval 12.9 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
9.49 months
Interval 8.2 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
27.96 months
Interval 10.9 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
32.30 months
Interval 2.4 to 32.3
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: EIF4EBP1 Nucleus
|
—
|
NA months
The median and the upper and lower 95% confidence interval were not estimable because of the high rate of censoring.
|
NA months
Interval 12.9 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
10.55 months
Interval 4.5 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: EIF4E Cytoplasm
|
NA months
Interval 4.3 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
21.42 months
Interval 2.4 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
27.96 months
Interval 17.1 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
NA months
Interval 4.5 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: EIF4E Nucleus
|
—
|
4.50 months
The upper and lower 95% confidence interval was not estimable because of the high rate of censoring.
|
NA months
Interval 12.9 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
32.30 months
Interval 8.9 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: HDAC2 Nucleus
|
27.96 months
Interval 4.3 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
10.55 months
Interval 8.2 to 32.3
|
NA months
Interval 12.9 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
NA months
Interval 2.4 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: PCREB Nucleus
|
24.10 months
Interval 4.3 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
10.55 months
Interval 2.4 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
NA months
Interval 12.9 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
NA months
The median and the upper and lower 95% confidence interval were not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: PEIF3746 Cytoplasm
|
27.96 months
Interval 8.2 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
20.90 months
Interval 4.5 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
NA months
Interval 4.3 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
NA months
Interval 2.4 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: PEIF3746 Nucleus
|
NA months
Interval 8.2 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
NA months
Interval 4.5 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
NA months
Interval 4.3 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
32.30 months
Interval 2.4 to 32.3
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: PEIFS209 Cytoplasm
|
NA months
Interval 4.3 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
9.20 months
Interval 2.4 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
27.96 months
Interval 8.2 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
NA months
Interval 10.5 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: PEIFS65 Nucleus
|
NA months
Interval 4.3 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
NA months
Interval 8.9 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
27.96 months
Interval 20.2 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
32.30 months
Interval 2.4 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: PEIFT70 Cytoplasm
|
NA months
Interval 8.2 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
NA months
Interval 8.9 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
27.96 months
Interval 10.9 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
10.55 months
Interval 2.4 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: PEIFT70 Nucleus
|
NA months
Interval 4.3 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
32.30 months
Interval 2.4 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
27.96 months
Interval 10.9 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
NA months
Interval 10.5 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: P GSK3B Cytoplasm
|
27.96 months
Interval 10.9 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
21.42 months
Interval 2.4 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
NA months
Interval 8.2 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
9.49 months
Interval 4.5 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: PKCb2 Cytoplasm
|
27.96 months
Interval 4.3 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
10.55 months
Interval 2.4 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
NA months
Interval 10.9 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
20.90 months
Interval 8.2 to 32.3
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: PS6 Cytoplasm
|
NA months
Interval 10.9 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
10.02 months
Interval 4.5 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
16.57 months
Interval 12.9 to 20.2
|
NA months
Interval 2.4 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: PTEN Cytoplasm
|
27.96 months
Interval 8.2 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
21.42 months
Interval 4.5 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
NA months
Interval 4.3 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
9.49 months
Interval 2.4 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
|
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS
Marker: PTEN Nucleus
|
27.96 months
Interval 10.9 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
6.34 months
Interval 4.5 to 8.2
|
NA months
Interval 8.2 to
The median and upper 95% confidence interval were not estimable because of the high rate of censoring.
|
32.30 months
Interval 8.9 to
The upper 95% confidence interval was not estimable because of the high rate of censoring.
|
Adverse Events
R-CHOP and Enzastaurin
Serious events: 35 serious events
Other events: 56 other events
Deaths: 0 deaths
R-CHOP
Serious events: 18 serious events
Other events: 43 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
R-CHOP and Enzastaurin
n=57 participants at risk
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.
|
R-CHOP
n=43 participants at risk
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
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.0%
4/57 • Number of events 4
|
2.3%
1/43 • Number of events 1
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
15.8%
9/57 • Number of events 12
|
7.0%
3/43 • Number of events 5
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
3.5%
2/57 • Number of events 2
|
7.0%
3/43 • Number of events 4
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.8%
1/57 • Number of events 1
|
4.7%
2/43 • Number of events 2
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
1.8%
1/57 • Number of events 1
|
4.7%
2/43 • Number of events 3
|
|
Cardiac disorders
Atrioventricular block
|
1.8%
1/57 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Cardiac disorders
Cardio-respiratory arrest
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Abdominal pain
|
3.5%
2/57 • Number of events 2
|
0.00%
0/43
|
|
Gastrointestinal disorders
Anal fistula
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Constipation
|
3.5%
2/57 • Number of events 2
|
0.00%
0/43
|
|
Gastrointestinal disorders
Diarrhoea
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Diverticular perforation
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Dysphagia
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
3.5%
2/57 • Number of events 2
|
0.00%
0/43
|
|
Gastrointestinal disorders
Nausea
|
1.8%
1/57 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Oesophageal disorder
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Oesophageal ulcer haemorrhage
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Asthenia
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
General disorders
Fatigue
|
1.8%
1/57 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Multi-organ failure
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
General disorders
Pain
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
General disorders
Pyrexia
|
5.3%
3/57 • Number of events 3
|
9.3%
4/43 • Number of events 4
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Alpha haemolytic streptococcal infection
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Infections and infestations
Bacteraemia
|
3.5%
2/57 • Number of events 2
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Cellulitis
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Infections and infestations
Cellulitis orbital
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Infections and infestations
Infection
|
1.8%
1/57 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Neutropenic sepsis
|
1.8%
1/57 • Number of events 2
|
0.00%
0/43
|
|
Infections and infestations
Pneumonia
|
8.8%
5/57 • Number of events 5
|
4.7%
2/43 • Number of events 2
|
|
Infections and infestations
Pneumonia streptococcal
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Infections and infestations
Sepsis
|
3.5%
2/57 • Number of events 2
|
9.3%
4/43 • Number of events 5
|
|
Infections and infestations
Septic shock
|
1.8%
1/57 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Tooth abscess
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Infections and infestations
Urinary tract infection
|
3.5%
2/57 • Number of events 2
|
4.7%
2/43 • Number of events 2
|
|
Infections and infestations
Urosepsis
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Viral upper respiratory tract infection
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Injury, poisoning and procedural complications
Fall
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Investigations
Haemoglobin decreased
|
1.8%
1/57 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Investigations
Weight decreased
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Metabolism and nutrition disorders
Dehydration
|
3.5%
2/57 • Number of events 2
|
0.00%
0/43
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Nervous system disorders
Hypoaesthesia
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Nervous system disorders
Neuropathy peripheral
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Nervous system disorders
Syncope
|
3.5%
2/57 • Number of events 3
|
0.00%
0/43
|
|
Psychiatric disorders
Depression
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Psychiatric disorders
Mental status changes
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Renal and urinary disorders
Renal failure acute
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
3.5%
2/57 • Number of events 2
|
2.3%
1/43 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
3.5%
2/57 • Number of events 2
|
2.3%
1/43 • Number of events 1
|
|
Vascular disorders
Hypertension
|
1.8%
1/57 • Number of events 1
|
0.00%
0/43
|
|
Vascular disorders
Hypotension
|
5.3%
3/57 • Number of events 3
|
0.00%
0/43
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/57
|
2.3%
1/43 • Number of events 1
|
Other adverse events
| Measure |
R-CHOP and Enzastaurin
n=57 participants at risk
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.
|
R-CHOP
n=43 participants at risk
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
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
38.6%
22/57 • Number of events 26
|
32.6%
14/43 • Number of events 16
|
|
Blood and lymphatic system disorders
Leukopenia
|
28.1%
16/57 • Number of events 40
|
32.6%
14/43 • Number of events 33
|
|
Blood and lymphatic system disorders
Lymphopenia
|
7.0%
4/57 • Number of events 8
|
0.00%
0/43
|
|
Blood and lymphatic system disorders
Neutropenia
|
57.9%
33/57 • Number of events 77
|
60.5%
26/43 • Number of events 59
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
28.1%
16/57 • Number of events 38
|
41.9%
18/43 • Number of events 38
|
|
Cardiac disorders
Palpitations
|
5.3%
3/57 • Number of events 3
|
4.7%
2/43 • Number of events 2
|
|
Eye disorders
Lacrimation increased
|
10.5%
6/57 • Number of events 8
|
9.3%
4/43 • Number of events 6
|
|
Eye disorders
Periorbital oedema
|
5.3%
3/57 • Number of events 10
|
0.00%
0/43
|
|
Eye disorders
Vision blurred
|
8.8%
5/57 • Number of events 8
|
9.3%
4/43 • Number of events 5
|
|
Gastrointestinal disorders
Abdominal pain
|
12.3%
7/57 • Number of events 8
|
9.3%
4/43 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.3%
3/57 • Number of events 4
|
0.00%
0/43
|
|
Gastrointestinal disorders
Constipation
|
38.6%
22/57 • Number of events 22
|
41.9%
18/43 • Number of events 25
|
|
Gastrointestinal disorders
Diarrhoea
|
47.4%
27/57 • Number of events 35
|
34.9%
15/43 • Number of events 18
|
|
Gastrointestinal disorders
Dyspepsia
|
7.0%
4/57 • Number of events 4
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
5.3%
3/57 • Number of events 3
|
0.00%
0/43
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
3.5%
2/57 • Number of events 2
|
9.3%
4/43 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
50.9%
29/57 • Number of events 46
|
44.2%
19/43 • Number of events 28
|
|
Gastrointestinal disorders
Stomatitis
|
33.3%
19/57 • Number of events 28
|
23.3%
10/43 • Number of events 13
|
|
Gastrointestinal disorders
Vomiting
|
19.3%
11/57 • Number of events 15
|
7.0%
3/43 • Number of events 3
|
|
General disorders
Asthenia
|
15.8%
9/57 • Number of events 11
|
11.6%
5/43 • Number of events 6
|
|
General disorders
Chills
|
10.5%
6/57 • Number of events 6
|
7.0%
3/43 • Number of events 5
|
|
General disorders
Fatigue
|
52.6%
30/57 • Number of events 37
|
67.4%
29/43 • Number of events 40
|
|
General disorders
Oedema
|
5.3%
3/57 • Number of events 3
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Oedema peripheral
|
31.6%
18/57 • Number of events 30
|
23.3%
10/43 • Number of events 10
|
|
General disorders
Pain
|
8.8%
5/57 • Number of events 5
|
7.0%
3/43 • Number of events 3
|
|
General disorders
Pyrexia
|
22.8%
13/57 • Number of events 18
|
16.3%
7/43 • Number of events 7
|
|
Infections and infestations
Candidiasis
|
7.0%
4/57 • Number of events 5
|
4.7%
2/43 • Number of events 2
|
|
Infections and infestations
Oral candidiasis
|
5.3%
3/57 • Number of events 3
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
5.3%
3/57 • Number of events 3
|
0.00%
0/43
|
|
Infections and infestations
Staphylococcal infection
|
5.3%
3/57 • Number of events 3
|
0.00%
0/43
|
|
Infections and infestations
Upper respiratory tract infection
|
10.5%
6/57 • Number of events 7
|
0.00%
0/43
|
|
Infections and infestations
Urinary tract infection
|
14.0%
8/57 • Number of events 11
|
2.3%
1/43 • Number of events 2
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
8.7%
2/23 • Number of events 2
|
0.00%
0/21
|
|
Investigations
Alanine aminotransferase increased
|
5.3%
3/57 • Number of events 4
|
4.7%
2/43 • Number of events 2
|
|
Investigations
Blood creatinine increased
|
7.0%
4/57 • Number of events 7
|
2.3%
1/43 • Number of events 1
|
|
Investigations
Haemoglobin decreased
|
8.8%
5/57 • Number of events 5
|
0.00%
0/43
|
|
Investigations
Neutrophil count decreased
|
5.3%
3/57 • Number of events 3
|
0.00%
0/43
|
|
Investigations
Platelet count decreased
|
5.3%
3/57 • Number of events 4
|
0.00%
0/43
|
|
Investigations
Weight decreased
|
15.8%
9/57 • Number of events 9
|
7.0%
3/43 • Number of events 3
|
|
Investigations
Weight increased
|
10.5%
6/57 • Number of events 6
|
2.3%
1/43 • Number of events 1
|
|
Investigations
White blood cell count decreased
|
5.3%
3/57 • Number of events 6
|
2.3%
1/43 • Number of events 1
|
|
Metabolism and nutrition disorders
Decreased appetite
|
24.6%
14/57 • Number of events 17
|
11.6%
5/43 • Number of events 5
|
|
Metabolism and nutrition disorders
Dehydration
|
15.8%
9/57 • Number of events 14
|
14.0%
6/43 • Number of events 7
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
5.3%
3/57 • Number of events 4
|
9.3%
4/43 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
5.3%
3/57 • Number of events 4
|
2.3%
1/43 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
5.3%
3/57 • Number of events 3
|
2.3%
1/43 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
8.8%
5/57 • Number of events 6
|
2.3%
1/43 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
5.3%
3/57 • Number of events 3
|
4.7%
2/43 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.3%
3/57 • Number of events 3
|
7.0%
3/43 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
17.5%
10/57 • Number of events 13
|
11.6%
5/43 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
17.5%
10/57 • Number of events 12
|
9.3%
4/43 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
14.0%
8/57 • Number of events 8
|
9.3%
4/43 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.3%
3/57 • Number of events 4
|
0.00%
0/43
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
3.5%
2/57 • Number of events 2
|
7.0%
3/43 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.3%
3/57 • Number of events 3
|
2.3%
1/43 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.0%
4/57 • Number of events 5
|
7.0%
3/43 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
19.3%
11/57 • Number of events 12
|
0.00%
0/43
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
5.3%
3/57 • Number of events 3
|
4.7%
2/43 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
29.8%
17/57 • Number of events 20
|
11.6%
5/43 • Number of events 6
|
|
Nervous system disorders
Dysgeusia
|
17.5%
10/57 • Number of events 11
|
9.3%
4/43 • Number of events 4
|
|
Nervous system disorders
Headache
|
15.8%
9/57 • Number of events 12
|
7.0%
3/43 • Number of events 4
|
|
Nervous system disorders
Memory impairment
|
7.0%
4/57 • Number of events 4
|
2.3%
1/43 • Number of events 1
|
|
Nervous system disorders
Neuropathy peripheral
|
31.6%
18/57 • Number of events 23
|
18.6%
8/43 • Number of events 9
|
|
Nervous system disorders
Paraesthesia
|
7.0%
4/57 • Number of events 4
|
2.3%
1/43 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
14.0%
8/57 • Number of events 8
|
14.0%
6/43 • Number of events 6
|
|
Psychiatric disorders
Anxiety
|
5.3%
3/57 • Number of events 3
|
4.7%
2/43 • Number of events 2
|
|
Psychiatric disorders
Depression
|
5.3%
3/57 • Number of events 3
|
4.7%
2/43 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
19.3%
11/57 • Number of events 11
|
20.9%
9/43 • Number of events 10
|
|
Renal and urinary disorders
Chromaturia
|
8.8%
5/57 • Number of events 5
|
0.00%
0/43
|
|
Renal and urinary disorders
Nocturia
|
7.0%
4/57 • Number of events 4
|
2.3%
1/43 • Number of events 1
|
|
Renal and urinary disorders
Pollakiuria
|
5.3%
3/57 • Number of events 3
|
2.3%
1/43 • Number of events 1
|
|
Renal and urinary disorders
Urinary incontinence
|
5.3%
3/57 • Number of events 3
|
0.00%
0/43
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.5%
10/57 • Number of events 12
|
18.6%
8/43 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
17.5%
10/57 • Number of events 11
|
25.6%
11/43 • Number of events 13
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
7.0%
4/57 • Number of events 5
|
2.3%
1/43 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.3%
3/57 • Number of events 3
|
7.0%
3/43 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
15.8%
9/57 • Number of events 9
|
11.6%
5/43 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
45.6%
26/57 • Number of events 26
|
39.5%
17/43 • Number of events 17
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.3%
3/57 • Number of events 4
|
0.00%
0/43
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
7.0%
4/57 • Number of events 4
|
2.3%
1/43 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.8%
9/57 • Number of events 10
|
11.6%
5/43 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
8.8%
5/57 • Number of events 5
|
0.00%
0/43
|
|
Vascular disorders
Deep vein thrombosis
|
3.5%
2/57 • Number of events 2
|
9.3%
4/43 • Number of events 4
|
|
Vascular disorders
Hypertension
|
1.8%
1/57 • Number of events 2
|
7.0%
3/43 • Number of events 3
|
|
Vascular disorders
Hypotension
|
10.5%
6/57 • Number of events 6
|
9.3%
4/43 • Number of events 6
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60