Trial Outcomes & Findings for Study to Assess the Effectiveness of RCHOP With or Without VELCADE in Previously Untreated Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients (NCT NCT00931918)

NCT ID: NCT00931918

Last Updated: 2017-01-11

Results Overview

PFS is defined as the time in months from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause. The date of progression is the earliest date of a computed tomography/positron emission tomography (CT/PET) scan that shows evidence of PD. For a participant that has not progressed and is alive at the end of his/her study follow-up or at the time of start of an alternate therapy (whichever is first), PFS is censored at the last overall response assessment that is stable disease or better, and which is prior to the start of the alternate therapy, if any. Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. PD= any new lesion or increase by \> 50% of previously involved sites from nadir.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

206 participants

Primary outcome timeframe

Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm

Results posted on

2017-01-11

Participant Flow

Participants took part in the study at 69 investigative sites in the United States from 13 October 2009 to 15 August 2015.

Participants with a diagnosis of Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma were enrolled equally in 1 of 2 treatment groups: RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] or Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] for 6, 21 day cycles.

Participant milestones

Participant milestones
Measure	RCHOP RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Overall Study STARTED	103	103
Overall Study Safety Population: Received Study Drug	100	101
Overall Study COMPLETED	86	86
Overall Study NOT COMPLETED	17	17

Reasons for withdrawal

Reasons for withdrawal
Measure	RCHOP RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Overall Study Adverse Event	4	6
Overall Study Progressive Disease	2	1
Overall Study Symptomatic Deterioration	1	0
Overall Study Withdrawal by Patient	3	4
Overall Study Other Reason not Specified	4	4
Overall Study Did not receive study drug	3	2

Baseline Characteristics

Study to Assess the Effectiveness of RCHOP With or Without VELCADE in Previously Untreated Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RCHOP n=100 Participants RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP n=101 Participants Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Total n=201 Participants Total of all reporting groups
Age, Continuous	59.8 years STANDARD_DEVIATION 14.60 • n=5 Participants	61.9 years STANDARD_DEVIATION 13.81 • n=7 Participants	60.9 years STANDARD_DEVIATION 14.21 • n=5 Participants
Age, Customized ≤ 65 years	58 participants n=5 Participants	55 participants n=7 Participants	113 participants n=5 Participants
Age, Customized > 65 years	42 participants n=5 Participants	46 participants n=7 Participants	88 participants n=5 Participants
Gender Female	43 Participants n=5 Participants	51 Participants n=7 Participants	94 Participants n=5 Participants
Gender Male	57 Participants n=5 Participants	50 Participants n=7 Participants	107 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	14 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	90 Participants n=5 Participants	82 Participants n=7 Participants	172 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized White	77 participants n=5 Participants	79 participants n=7 Participants	156 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	10 participants n=5 Participants	9 participants n=7 Participants	19 participants n=5 Participants
Race/Ethnicity, Customized Asian	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Race/Ethnicity, Customized Other	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Not Reported	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment United States	100 participants n=5 Participants	101 participants n=7 Participants	201 participants n=5 Participants
Height	171.1 cm STANDARD_DEVIATION 11.30 • n=5 Participants	170.3 cm STANDARD_DEVIATION 11.48 • n=7 Participants	170.7 cm STANDARD_DEVIATION 11.37 • n=5 Participants
Weight	85.19 kg STANDARD_DEVIATION 20.684 • n=5 Participants	82.86 kg STANDARD_DEVIATION 21.745 • n=7 Participants	84.02 kg STANDARD_DEVIATION 21.203 • n=5 Participants
Body Surface Area	2.002 m^2 STANDARD_DEVIATION 0.2830 • n=5 Participants	1.970 m^2 STANDARD_DEVIATION 0.3040 • n=7 Participants	1.986 m^2 STANDARD_DEVIATION 0.2934 • n=5 Participants

PRIMARY outcome

Timeframe: Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm

Population: Modified Intent-to-treat (mITT) Population included all randomized participants who received study drug and who had a central laboratory-confirmed Non-Germinal Center B-Cell (non-GCB) subtype.

Outcome measures

Outcome measures
Measure	RCHOP n=91 Participants RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP n=92 Participants Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Progression-Free Survival (PFS) in Patients With Non-germinal Center B-cell-like (Non-GCB) Diffuse Large B-cell Lymphoma (DLBCL)	NA months Median not estimable due to the low number of participants with events.	NA months Median not estimable due to the low number of participants with events.

PRIMARY outcome

Timeframe: 2 Years (Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm)

Outcome measures

Outcome measures
Measure	RCHOP n=91 Participants RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP n=92 Participants Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Progression-Free Survival Rate	78 percentage of participants	82 percentage of participants

SECONDARY outcome

Timeframe: Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm

Population: MITT Population included all randomized participants who received study drug and who had a central laboratory-confirmed Non-Germinal Center B-Cell (non-GCB) subtype.

Overall survival is defined as the time from the date of randomization to the date of death from any cause. A participant who is alive at the end of his/her study follow-up is censored at the date of last contact.

Outcome measures

Outcome measures
Measure	RCHOP n=91 Participants RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP n=92 Participants Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Overall Survival	NA months Median not estimable due to the low number of participants with events.	NA months Median not estimable due to the low number of participants with events.

SECONDARY outcome

Timeframe: End of Cycle 2, End of Treatment (Cycle 6) [Median of 16 weeks on treatment]

Population: Response-Evaluable Population included all randomized participants who had at least 1 dose of study drug, who had a central laboratory-confirmed non-GCB subtype with measurable disease at Baseline and at least 1 post-baseline response assessment.

ORR is defined as the percentage of participants with the best overall response complete response (CR) + partial response (PR). Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. CR=disappearance of all evidence of disease and PR=regression of measurable disease and no new sites.

Outcome measures

Outcome measures
Measure	RCHOP n=86 Participants RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP n=90 Participants Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Overall Response Rate (ORR) End of Cycle 2	93 percentage of participants Interval 86.0 to 97.0	90 percentage of participants Interval 82.0 to 95.0
Overall Response Rate (ORR) End of Treatment (Cycle 6)	88 percentage of participants Interval 80.0 to 94.0	84 percentage of participants Interval 76.0 to 91.0
Overall Response Rate (ORR) Best Overall Response Rate	98 percentage of participants Interval 92.0 to 99.0	96 percentage of participants Interval 89.0 to 98.0

SECONDARY outcome

Timeframe: End of Cycle 2, End of Treatment (Cycle 6) [Median of 16 weeks on treatment]

Complete Response Rate is defined as the percentage of participants with the best response of Complete Response (CR). Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. CR=Disappearance of all evidence of disease.

Outcome measures

Outcome measures
Measure	RCHOP n=86 Participants RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP n=90 Participants Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Complete Response Rate End of Cycle 2	23 percentage of participants Interval 16.0 to 33.0	16 percentage of participants Interval 9.0 to 24.0
Complete Response Rate End of Treatment (Cycle 6)	45 percentage of participants Interval 35.0 to 56.0	56 percentage of participants Interval 45.0 to 65.0
Complete Response Rate Best Complete Response Rate	49 percentage of participants Interval 39.0 to 59.0	56 percentage of participants Interval 45.0 to 65.0

SECONDARY outcome

Timeframe: Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm

Population: Participants from the Response-Evaluable Population included all randomized participants who had at least 1 dose of study drug, who had a central laboratory-confirmed non-GCB subtype with measurable disease at Baseline and at least 1 post-baseline response assessment who had a CR or PR

Duration of response is defined as the time (in months) from the date of first documentation of confirmed complete response (CR) or partial response (PR) to the date of first documentation of progressive disease (PD), relapse from CR or death related to disease. For a participant who has not progressed and is not known to have died due to disease under study at the end of his/her study follow-up or at the time of start of an alternate therapy (whichever is first), duration of response is censored at the last overall response assessment that is stable disease or better, and which is prior to the start of the alternate therapy, if any. Disease response was assessed using IWG-revised response criteria for malignant lymphoma. CR=Disappearance of all evidence of disease and PR=Regression of measurable disease and no new sites and PD= any new lesion or increase by \> 50% of previously involved sites from nadir.

Outcome measures

Outcome measures
Measure	RCHOP n=84 Participants RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP n=86 Participants Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Duration of Response	NA months Median not estimable due to the low number of participants with events.	NA months Median not estimable due to the low number of participants with events.

SECONDARY outcome

Timeframe: End of Cycle 2 and End of Treatment (Cycle 6) [Median of 16 weeks on treatment]

FDG-PET negative rate is defined as the percentage of participants FDG-PET negative at the given time-point.

Outcome measures

Outcome measures
Measure	RCHOP n=86 Participants RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP n=90 Participants Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Negative Rate End of Cycle 2	42 percentage of participants Interval 32.0 to 52.0	37 percentage of participants Interval 27.0 to 47.0
Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Negative Rate End of Treatment (Cycle 6)	53 percentage of participants Interval 43.0 to 64.0	59 percentage of participants Interval 49.0 to 68.0

SECONDARY outcome

Timeframe: Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm

Population: MITT Population included all randomized participants who received study drug and who had a central laboratory-confirmed Non-Germinal Center B-Cell (non-GCB) subtype.

TTP is defined as the time from the date of randomization to the date of first documentation of progressive disease, relapse from CR, or death related to disease under study if participant did not have any documentation of disease progression prior to death caused by lymphoma or complications thereof. For a participant who has not progressed and is not known to have died due to disease under study at the end of his/her study follow-up or at the time of start of an alternate therapy (whichever is first), TTP is censored at the last overall response assessment that is stable disease or better, and which is prior to the start of the alternate therapy, if any. Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. PD= any new lesion or increase by \> 50% of previously involved sites from nadir.

Outcome measures

Outcome measures
Measure	RCHOP n=91 Participants RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP n=92 Participants Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Time to Progression (TTP)	NA months Median is not estimable due to the low number of participant with events.	NA months Median is not estimable due to the low number of participant with events.

SECONDARY outcome

Timeframe: First dose of study drug through 30 days after the last dose of study drug (Up to 26 Weeks)

Population: Safety Population included all randomized participants who received at least 1 dose of study drug.

Percentage of participants in the following categories: • At least 1 TEAE • Drug-related, TEAEs • Grade 3 or higher TEAEs. Grade 3 are AEs of Severe Intensity • Grade 3 or higher drug-related, TEAEs • TEAEs resulting in study drug discontinuation • Serious TEAEs An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Outcome measures
Measure	RCHOP n=100 Participants RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP n=101 Participants Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) by Category At Least 1 TEAE	100 percentage of participants	99 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) by Category Drug-related, TEAEs	88 percentage of participants	95 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) by Category Grade 3 or higher TEAEs	71 percentage of participants	79 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) by Category Grade 3 or Higher Drug-related, TEAEs	55 percentage of participants	68 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) by Category TEAEs Resulting in Study Drug Discontinuation	4 percentage of participants	6 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) by Category Serious TEAEs	31 percentage of participants	34 percentage of participants

SECONDARY outcome

Timeframe: Days 1, 4 and 10 of each cycle and end of treatment visit (Median of 16 weeks on treatment)

Population: Safety Population included all randomized participants who received at least 1 dose of study drug.

Percentage of participants who shifted from a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 0, 1, or 2 at Baseline to a Grade 3 or higher on study (worst post-baseline grade). Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=Life-threatening consequences and 5=Death related to AE.

Outcome measures

Outcome measures
Measure	RCHOP n=100 Participants RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.	Vc-RCHOP n=101 Participants Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher Lymphocytes	70 percentage of participants	86 percentage of participants
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher WBC Count	68 percentage of participants	69 percentage of participants
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher Neutrophils	65 percentage of participants	70 percentage of participants
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher Platelets	18 percentage of participants	39 percentage of participants
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher Hemoglobin	10 percentage of participants	15 percentage of participants
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher Hyperglycemia	14 percentage of participants	9 percentage of participants
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher Hypokalemia	13 percentage of participants	14 percentage of participants
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher Hypophosphatemia	7 percentage of participants	10 percentage of participants
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher Hyponatremia	4 percentage of participants	3 percentage of participants
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher Alanine aminotransferase (ALT) increased	2 percentage of participants	1 percentage of participants
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher Aspartate aminotransferase (AST) increased	1 percentage of participants	2 percentage of participants

Adverse Events

RCHOP

Serious events: 31 serious events

Other events: 100 other events

Deaths: 0 deaths

Vc-RCHOP

Serious events: 34 serious events

Other events: 100 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
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Restriction type: OTHER