Trial Outcomes & Findings for Study of the Combination of Rituximab, Cyclophosphamide, Doxorubicin, VELCADE, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Mantle Cell Lymphoma (NCT NCT00722137)
NCT ID: NCT00722137
Last Updated: 2018-07-12
Results Overview
PFS was defined as the interval between the date of randomization and the date of progressive disease (PD) or death, whichever occurred first. PD was based on the assessment of an Independent Review Committee.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
487 participants
Primary outcome timeframe
Median duration of follow-up of 40 months
Results posted on
2018-07-12
Participant Flow
A total of 487 participants were randomized from 128 centers in 28 countries from 22 May 2008 to 17 June 2017; 244 to the R-CHOP treatment group and 243 to the VcR-CAP treatment group. Of the 487 randomized participants, 242 in the R-CHOP group and 240 in the VcR-CAP group received at least 1 dose of study drug.
Participant milestones
| Measure |
R-CHOP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Overall Study
STARTED
|
244
|
243
|
|
Overall Study
COMPLETED
|
199
|
195
|
|
Overall Study
NOT COMPLETED
|
45
|
48
|
Reasons for withdrawal
| Measure |
R-CHOP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Overall Study
Overt Disease Progression
|
5
|
4
|
|
Overall Study
Adverse Event
|
17
|
21
|
|
Overall Study
Death
|
12
|
7
|
|
Overall Study
Withdrawal by Subject
|
6
|
9
|
|
Overall Study
Other Reason Unknown
|
3
|
4
|
|
Overall Study
Randomized But Not Treated
|
2
|
3
|
Baseline Characteristics
Study of the Combination of Rituximab, Cyclophosphamide, Doxorubicin, VELCADE, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Mantle Cell Lymphoma
Baseline characteristics by cohort
| Measure |
R-CHOP
n=244 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=243 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
Total
n=487 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.4 Years
STANDARD_DEVIATION 8.78 • n=5 Participants
|
64.2 Years
STANDARD_DEVIATION 9.68 • n=7 Participants
|
64.3 Years
STANDARD_DEVIATION 9.23 • n=5 Participants
|
|
Sex: Female, Male
Female
|
62 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
127 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
182 Participants
n=5 Participants
|
178 Participants
n=7 Participants
|
360 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
68 Participants
n=5 Participants
|
88 Participants
n=7 Participants
|
156 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
172 Participants
n=5 Participants
|
151 Participants
n=7 Participants
|
323 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
10 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
5 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
5 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
7 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
Portugal
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
Russia
|
57 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
|
Region of Enrollment
China
|
34 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
18 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
9 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Region of Enrollment
Thailand
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
11 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
India
|
9 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
Tunisia
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
Turkey
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
Colombia
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic Of
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
Chile
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
Singapore
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
Taiwan, Province Of China
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Median duration of follow-up of 40 monthsPopulation: The population consisted of all randomized participants.
PFS was defined as the interval between the date of randomization and the date of progressive disease (PD) or death, whichever occurred first. PD was based on the assessment of an Independent Review Committee.
Outcome measures
| Measure |
R-CHOP
n=244 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=243 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Progression Free Survival (PFS)
|
437.0 Days
Interval 365.0 to 513.0
|
751.0 Days
Interval 604.0 to 969.0
|
SECONDARY outcome
Timeframe: Median duration of follow-up of 40 monthsPopulation: The population consisted of all randomized participants.
Time to progression was defined as the duration from the date of randomization until the date of first documented evidence of progressive disease (PD) or date of relapse for subjects who experienced complete response (CR) or complete response, unconfirmed (CRu). PD and response were based on the assessment of an Independent Review Committee.
Outcome measures
| Measure |
R-CHOP
n=244 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=243 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Time to Progression (TTP)
|
490.0 Days
Interval 417.0 to 550.0
|
929.0 Days
Interval 696.0 to 1245.0
|
SECONDARY outcome
Timeframe: Median duration of follow-up of 40 monthsPopulation: The response-evaluable population was defined as all participants who received at least 1 dose of study drug, had \>= 1 measurable tumor mass (\>1.5 cm in the longest dimension and \>1.0 cm in the short axis) at baseline and had at least 1 post-baseline tumor assessment by Independent Review Committee, before any subsequent anti-lymphoma treatment.
The duration of treatment response was defined as the time from the date of the first response to the date of PD or death due to PD for those participants with a best response of CR, CRu, or PR as determined by the Independent Review Committee. The duration of response for complete responders was defined as the time from the date of the first response to the date of PD or death due to PD for those participants with a best response of CR or CRu verified by bone marrow and lactate dehydrogenase (LDH).
Outcome measures
| Measure |
R-CHOP
n=228 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=229 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Duration of Response
Duration of response
|
459.0 Days
Interval 379.0 to 518.0
|
1110.0 Days
Interval 813.0 to 1320.0
|
|
Duration of Response
Duration for Complete responders
|
563.0 Days
Interval 486.0 to 738.0
|
1282.0 Days
Interval 933.0 to 1602.0
|
SECONDARY outcome
Timeframe: : Median duration of follow-up of 40 monthsPopulation: The population consisted of all randomized participants.
The time to next anti-lymphomatreatment was measured from the date of initiation of study treatment as per protocol to the start date of new anti-lymphoma treatment. Death due to disease progression prior to subsequent therapy was considered as an event. Otherwise, time to next anti lymphoma treatment was censored at the date of death or the last date known to be alive.
Outcome measures
| Measure |
R-CHOP
n=244 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=243 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Time to Next Anti-lymphoma Treatment (TTNT)
|
756.0 Days
Interval 674.0 to 837.0
|
1353.0 Days
Interval 1180.0 to
The upper limit of the confidence interval was not able to be estimated.
|
SECONDARY outcome
Timeframe: Median duration of follow-up of 40 monthsPopulation: All randomized participants who received at least 1 dose of study medication.
The TFI was defined as the duration from the date of last dose plus 1 day to the start date of the new treatment. Death due to disease progression prior to subsequent therapy was considered as an event. Otherwise, treatment-free interval was censored at the date of death or the last date known to be alive.
Outcome measures
| Measure |
R-CHOP
n=242 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=240 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Treatment-free Interval (TFI)
|
624.0 Days
Interval 542.0 to 693.0
|
1236.0 Days
Interval 1023.0 to
The upper limit of the confidence interval was not able to be estimated.
|
SECONDARY outcome
Timeframe: Median duration of follow-up of 40 monthsPopulation: The response-evaluable population was defined as all participants who received \>= 1 dose of study drug, had at least 1 measurable tumor mass (\>1.5 cm in the longest dimension and \>1.0 cm in the short axis) at baseline and had at least 1 post-baseline tumor assessment by Independent Review Committee, before any subsequent anti-lymphoma treatment.
ORR was defined as complete response (CR) + complete response, unconfirmed (CRu) + partial response (PR) as determined by the Independent Review Committee. Response assessment was carried out every 6 weeks for 18 weeks; thereafter, every 8 weeks until PD/initiation of alternate therapy/withdrawal from study/death.
Outcome measures
| Measure |
R-CHOP
n=228 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=229 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Overall Response Rate (ORR)
|
204 Participants
|
211 Participants
|
SECONDARY outcome
Timeframe: Median duration of follow-up of 40 monthsPopulation: The response-evaluable population was defined as all participants who received \>= 1 dose of study drug, had at least 1 measurable tumor mass (\>1.5 cm in the longest dimension and \>1.0 cm in the short axis) at baseline and had at least 1 post-baseline tumor assessment by Independent Review Committee, before any subsequent anti-lymphoma treatment.
Overall complete response was defined as the number of participants with complete response (CR) and those with unconfirmed complete response (CRu). Response assessment was carried out every 6 weeks for 18 weeks; thereafter, every 8 weeks until PD/initiation of alternate therapy/withdrawal from study/death.
Outcome measures
| Measure |
R-CHOP
n=228 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=229 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Overall Complete Response (CR + CRu)
Overall complete response
|
95 Participants
|
122 Participants
|
|
Overall Complete Response (CR + CRu)
CR
|
79 Participants
|
106 Participants
|
|
Overall Complete Response (CR + CRu)
CRu
|
16 Participants
|
16 Participants
|
SECONDARY outcome
Timeframe: Median duration of follow-up of 40 monthsPopulation: The population consisted of all randomized participants.
OS was measured from the date of randomization to the date of the participant's death. If the participant was alive or the vital status was unknown, OS was censored at the date that the subject was last known to be alive.
Outcome measures
| Measure |
R-CHOP
n=244 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=243 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Overall Survival (OS)
|
1714.0 Days
Interval 1436.0 to
The upper limit of the confidence interval was not able to be estimated.
|
NA Days
Interval 1704.0 to
The median was not reached and the upper limit of the confidence interval was not able to be estimated.
|
SECONDARY outcome
Timeframe: Up to month 18 from the time of randomizationPopulation: The population consisted of all randomized participants.
18-month survival was defined as the estimated probability of survival at 18 months (Kaplan-Meier estimate).
Outcome measures
| Measure |
R-CHOP
n=244 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=243 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
18-Month Survival
|
83.8 Percentage of Participants
Interval 78.4 to 87.9
|
84.9 Percentage of Participants
Interval 79.6 to 88.9
|
SECONDARY outcome
Timeframe: Up to 107.4 monthsPopulation: The population consisted of all randomized participants.
OS was measured from the date of randomization to the date of the participant's death. If the participant was alive or the vital status was unknown, OS was censored at the date that the subject was last known to be alive.
Outcome measures
| Measure |
R-CHOP
n=244 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=243 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Overall Survival (OS) in Long Term Follow-up Period
|
1695.0 Days
Interval 1436.0 to 2098.0
|
2760.0 Days
Interval 2172.0 to
Upper limit of overall survival after long term follow-up was not estimable due low number of participants with the event.
|
SECONDARY outcome
Timeframe: Up to 107.4 monthsPopulation: The safety population was defined as all randomized participants who received at least 1 dose of study medication.
An AE was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. AEs were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 8 cycles (24 weeks) and AEs were collected for up to 30 days following the last dose of study drug.
Outcome measures
| Measure |
R-CHOP
n=242 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=240 Participants
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Number of Participants Experiencing an Adverse Event (AE)
|
239 Participants
|
240 Participants
|
Adverse Events
R-CHOP
Serious events: 72 serious events
Other events: 187 other events
Deaths: 0 deaths
VcR-CAP
Serious events: 91 serious events
Other events: 185 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
R-CHOP
n=242 participants at risk
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=240 participants at risk
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Cardiac disorders
Acute left ventricular failure
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Cardiac arrest
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
8.3%
20/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
10.8%
26/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.4%
13/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
5.0%
12/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
3.3%
8/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.2%
3/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
2.5%
6/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Blood and lymphatic system disorders
Anaemia
|
2.1%
5/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
1.7%
4/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Blood and lymphatic system disorders
Bone marrow failure
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Pneumonia
|
2.9%
7/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
7.9%
19/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Sepsis
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
1.7%
4/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Bronchitis
|
0.83%
2/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Lobar pneumonia
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Lung infection
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Pneumonia streptococcal
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Septic shock
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Abscess neck
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Bronchopneumonia
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Candidiasis
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Erysipelas
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Hepatitis B
|
0.83%
2/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Herpes zoster
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Klebsiella sepsis
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Nosocomial infection
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Parotitis
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Pneumonia cytomegaloviral
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Postoperative abscess
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Pulmonary mycosis
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Respiratory tract infection
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Salmonellosis
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Anal abscess
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Bacterial sepsis
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Clostridium difficile infection
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Endocarditis bacterial
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Gastroenteritis
|
0.83%
2/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Oral fungal infection
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Oral herpes
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Oropharyngeal candidiasis
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Paronychia
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Peritonsillar abscess
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Rectal abscess
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Tracheobronchitis
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
1.7%
4/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
1.2%
3/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.1%
5/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Tonsillar haemorrhage
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.83%
2/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
General disorders
Pyrexia
|
1.7%
4/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
4.2%
10/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
General disorders
Acute phase reaction
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
General disorders
Asthenia
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
General disorders
Chills
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
General disorders
Death
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
General disorders
Cardiac death
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
General disorders
Chest pain
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
General disorders
Fatigue
|
1.2%
3/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
General disorders
Oedema peripheral
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.2%
3/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
1.7%
4/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Vomiting
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Abdominal adhesions
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Colitis
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Ileus paralytic
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Melaena
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Stomatitis
|
0.83%
2/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Anal fissure
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Constipation
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Haematemesis
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Periproctitis
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
1.2%
3/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Atrial fibrillation
|
0.83%
2/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Cardiogenic shock
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Myocardial ischaemia
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Supraventricular extrasystoles
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Cardiac failure acute
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.83%
2/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Cardiomyopathy
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Left ventricular failure
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Myocardial infarction
|
0.83%
2/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Tachycardia
|
0.83%
2/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Vascular disorders
Hypotension
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
1.2%
3/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Vascular disorders
Poor venous access
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Vascular disorders
Deep vein thrombosis
|
1.2%
3/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Vascular disorders
Hypertension
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Vascular disorders
Venous thrombosis
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Autonomic neuropathy
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Cerebral ischaemia
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Encephalitis
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Peripheral sensorimotor neuropathy
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Syncope
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Convulsion
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.83%
2/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Metabolism and nutrition disorders
Fluid retention
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
0.83%
2/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Hepatobiliary disorders
Bile duct stone
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Injury, poisoning and procedural complications
Compression fracture
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Injury, poisoning and procedural complications
Traumatic lung injury
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
Soft tissue necrosis
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Renal and urinary disorders
Renal failure
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Renal and urinary disorders
Renal impairment
|
0.41%
1/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
0.42%
1/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
Other adverse events
| Measure |
R-CHOP
n=242 participants at risk
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2 and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Vincristine: Vincristine intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles.
|
VcR-CAP
n=240 participants at risk
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2 Rituximab: Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles. Cyclophosphamide: Cyclophosphamide intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Doxorubicin: Intravenous on Day of a 21 day (3 week) cycle for 6 cycles VELCADE: VELCADE intravenous on Days 1,4,8, and 11 of a 21 day (3 week) cycle for 6 cycles Prednisone: Prednisone orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
13.6%
33/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
24.6%
59/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Abdominal distension
|
2.1%
5/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
9.2%
22/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Abdominal pain
|
3.7%
9/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
7.5%
18/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.5%
11/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
6.7%
16/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Dyspepsia
|
5.8%
14/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
5.4%
13/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Neuropathy peripheral
|
7.9%
19/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
7.9%
19/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Paraesthesia
|
5.0%
12/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
6.7%
16/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Dizziness
|
3.7%
9/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
6.2%
15/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Hypoaesthesia
|
6.2%
15/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
6.2%
15/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Headache
|
4.5%
11/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
5.4%
13/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.3%
20/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
20.4%
49/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
4.1%
10/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
5.8%
14/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
13.6%
33/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
13.8%
33/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.3%
8/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
5.4%
13/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.1%
5/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
8.3%
20/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.2%
15/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
6.2%
15/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
8.3%
20/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
7.5%
18/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
4.5%
11/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
5.8%
14/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Psychiatric disorders
Insomnia
|
7.4%
18/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
11.2%
27/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
|
Investigations
Weight decreased
|
4.1%
10/242 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
5.8%
14/240 • Up to 107.4 months
The safety population was defined as all randomized participants who received at least 1 dose of study medication.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
- Publication restrictions are in place
Restriction type: OTHER