Trial Outcomes & Findings for Study of Bendamustine Hydrochloride and Rituximab (BR) Compared With R-CVP or R-CHOP in the First-Line Treatment of Patients With Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL) - Referred to as the BRIGHT Study (NCT NCT00877006)

Last Updated: 2018-02-05

Results Overview

CR=complete disappearance of all detectable clinical evidence of disease and disease-related symptoms, if present pretherapy; protocol-specified positron emission tomography (PET) scan assessment criteria; (if the spleen and/or liver were enlarged on the basis of physical examination and/or anatomic imaging before treatment) the liver and/or spleen were considered normal size on physical examination and by anatomic imaging after therapy, with disappearance of all nodules related to lymphoma; (if the bone marrow was involved by lymphoma before treatment) the infiltrate must have cleared on subsequent bone marrow biopsies.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

447 participants

Primary outcome timeframe

6 to 8 21 or 28-day cycles (18-32 weeks)

Results posted on

2018-02-05

Participant Flow

A total of 568 participants were screened, and 121 were not randomized (2 due to adverse event, 14 withdrew consent, 68 did not meet inclusion criteria, 23 met exclusion criteria, and 14 for other reasons).

Participant milestones

Participant milestones
Measure	Bendamustine and Rituximab (BR) Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Treatment Period STARTED	224	223
Treatment Period COMPLETED	199	196
Treatment Period NOT COMPLETED	25	27
Long-Term Follow-up Period STARTED	210	209
Long-Term Follow-up Period COMPLETED	157	154
Long-Term Follow-up Period NOT COMPLETED	53	55

Reasons for withdrawal

Reasons for withdrawal
Measure	Bendamustine and Rituximab (BR) Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Treatment Period Death	2	1
Treatment Period Adverse Event	10	3
Treatment Period Withdrawal by Subject	2	3
Treatment Period Protocol Violation	1	0
Treatment Period Lost to Follow-up	0	1
Treatment Period Disease Progression	1	2
Treatment Period Started New Treatment Regimen	2	5
Treatment Period Other	4	4
Treatment Period Randomized but Not Treated	3	8
Long-Term Follow-up Period Withdrawal by Subject	12	19
Long-Term Follow-up Period Lost to Follow-up	8	9
Long-Term Follow-up Period Death	26	18
Long-Term Follow-up Period Other	7	9

Baseline Characteristics

Study of Bendamustine Hydrochloride and Rituximab (BR) Compared With R-CVP or R-CHOP in the First-Line Treatment of Patients With Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL) - Referred to as the BRIGHT Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bendamustine and Rituximab (BR) n=224 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=223 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5	Total n=447 Participants Total of all reporting groups
Age, Continuous	60.0 years STANDARD_DEVIATION 11.37 • n=5 Participants	58.2 years STANDARD_DEVIATION 12.11 • n=7 Participants	59.1 years STANDARD_DEVIATION 11.77 • n=5 Participants
Sex: Female, Male Female	88 Participants n=5 Participants	91 Participants n=7 Participants	179 Participants n=5 Participants
Sex: Female, Male Male	136 Participants n=5 Participants	132 Participants n=7 Participants	268 Participants n=5 Participants
European Cooperative Oncology Group Performance Status 0	144 participants n=5 Participants	143 participants n=7 Participants	287 participants n=5 Participants
European Cooperative Oncology Group Performance Status 1	70 participants n=5 Participants	69 participants n=7 Participants	139 participants n=5 Participants
European Cooperative Oncology Group Performance Status 2	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants
European Cooperative Oncology Group Performance Status 3	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
European Cooperative Oncology Group Performance Status 4	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Weight	81.9 kg STANDARD_DEVIATION 18.48 • n=5 Participants	82.4 kg STANDARD_DEVIATION 17.93 • n=7 Participants	82.1 kg STANDARD_DEVIATION 18.19 • n=5 Participants

PRIMARY outcome

Timeframe: 6 to 8 21 or 28-day cycles (18-32 weeks)

Population: Evaluable Analysis Set: treated participants with a baseline and \>=1 post-baseline response evaluation (based on computed tomography/magnetic resonance imaging \[CT/MRI\] or positron emission tomography \[PET\] and clinical data), or who discontinued treatment due to progressive disease and had no major protocol violations.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=213 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=206 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Percentage of Participants With Complete Response (CR) at End of Treatment Period	31 percentage of participants Interval 25.3 to 38.2	25 percentage of participants Interval 19.5 to 31.7

SECONDARY outcome

Timeframe: 6 to 8 21 or 28-day cycles (18-32 weeks)

Overall Response=participants with Complete Remission (CR) + those with Partial Remission (PR). CR=see Outcome Measure 1 for details. PR= at least a 50% decrease in the sum of the product of the greatest diameters (SPD) of up to 6 of the largest dominant nodes/masses; at least a 50% decrease in the SPD of hepatic and splenic nodules in their greatest transverse diameter; no increase in the size of the liver, spleen, and other nodes; no measurable disease in organs other than the liver or spleen; no new sites of disease; protocol-specified PET scan and bone marrow criteria.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=213 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=206 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Percentage of Participants With Overall Response at End of Treatment Period	97 percentage of participants Interval 93.3 to 98.7	91 percentage of participants Interval 86.0 to 94.4

SECONDARY outcome

Timeframe: 32 weeks

Population: Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen.

AE=any untoward medical occurrence that develops or worsens in severity after dispensation of the study drug and does not necessarily have a causal relationship to the study drug. An AE can, therefore, be any unfavorable and unintended physical sign, symptom, or laboratory parameter that develops or worsens in severity during the course of the study, or significant worsening of the disease under study (or any concurrent disease), whether or not considered related to the study drug. AEs were graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). SAE=an adverse event occurring at any dose that results in: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity (a substantial disruption of one's ability to conduct normal life functions), a congenital anomaly/birth defect, or other important medical event.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=221 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=215 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period Any AE	221 participants	213 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period Severe AEs (grades 3, 4, 5)	130 participants	127 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period Treatment-related AEs	209 participants	NA participants AE relationship was not assessed (not collected) for participants in the R-CHOP/R-CVP treatment group because it was open label and the events associated with R-CHOP/R-CVP arm were known due to being standard treatment for many countries.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period Deaths	12 participants	9 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period SAEs	60 participants	49 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period Withdrawn due to AEs	10 participants	3 participants

SECONDARY outcome

Timeframe: 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)

Population: Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen and who had a post-baseline assessment.

Clinical laboratory data were graded according to National Cancer Institute's (NCI) CTCAE version 3, and graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). The table presents the worst CTCAE grades for serum chemistry test results experienced by participants overall (i.e., the worst post-baseline grade value for each participant and laboratory test across all cycles).

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=221 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=215 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Total Bilirubin: Grade 1	14 participants	7 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Total Bilirubin: Grade 2	1 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Aspartate Aminotransferase: Grade 3	1 participants	1 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Aspartate Aminotransferase: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Aspartate Aminotransferase: Grades 1-4	45 participants	35 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Alanine Aminotransferase: Grade 1	46 participants	38 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Alanine Aminotransferase: Grade 2	6 participants	3 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Alanine Aminotransferase: Grade 3	2 participants	1 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Alanine Aminotransferase: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Alanine Aminotransferase: Grades 1-4	54 participants	42 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Alkaline Phosphatase: Grade 1	41 participants	25 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Alkaline Phosphatase: Grade 2	1 participants	3 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Alkaline Phosphatase: Grade 3	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Alkaline Phosphatase: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Alkaline Phosphatase: Grades 1-4	42 participants	28 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Creatinine: Grade 1	19 participants	25 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Creatinine: Grade 2	3 participants	1 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Creatinine: Grade 3	1 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Creatinine: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Creatinine: Grades 1-4	23 participants	26 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Gamma-glutamyl transferase: Grade 1	31 participants	37 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Gamma-glutamyl transferase: Grade 2	18 participants	10 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Gamma-glutamyl transferase: Grade 3	3 participants	6 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Gamma-glutamyl transferase: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Gamma-glutamyl transferase: Grades 1-4	52 participants	53 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypercalcemia: Grade 1	6 participants	6 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypercalcemia: Grade 2	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypercalcemia: Grade 3	1 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypercalcemia: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypercalcemia: Grades 1-4	7 participants	6 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyperglycemia: Grade 1	94 participants	74 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyperglycemia: Grade 2	20 participants	34 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyperglycemia: Grade 3	15 participants	15 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyperglycemia: Grade 4	0 participants	1 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyperglycemia: Grades 1-4	129 participants	124 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyperkalemia: Grade 1	7 participants	8 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyperkalemia: Grade 2	3 participants	1 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyperkalemia: Grade 3	1 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyperkalemia: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyperkalemia: Grades 1-4	11 participants	9 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypernatremia: Grade 1	8 participants	10 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypernatremia: Grade 2	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Magnesium: Grade 3	0 participants	1 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Magnesium: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Magnesium: Grades 1-4	46 participants	46 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Phosphorus: Grade 1	7 participants	5 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Phosphorus: Grade 2	25 participants	22 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Phosphorus: Grade 3	3 participants	3 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Phosphorus: Grade 4	0 participants	1 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Phosphorus: Grades 1-4	35 participants	31 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Aspartate Aminotransferase: Grade 1	42 participants	32 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Aspartate Aminotransferase: Grade 2	2 participants	2 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Total Bilirubin: Grade 3	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Total Bilirubin: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Total Bilirubin: Grades 1-4	15 participants	7 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Uric Acid: Grade 1	41 participants	42 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Uric Acid: Grade 2	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Uric Acid: Grade 3	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Uric Acid: Grade 4	1 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Uric Acid: Grades 1-4	42 participants	42 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypernatremia: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypernatremia: Grades 1-4	8 participants	10 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypernatremia: Grade 3	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypocalcemia: Grade 1	36 participants	28 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Albumin: Grade 1	33 participants	44 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Albumin: Grade 2	14 participants	13 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Albumin: Grade 3	3 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Albumin: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Albumin: Grades 1-4	50 participants	57 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypocalcemia: Grade 2	8 participants	6 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypocalcemia: Grade 3	1 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypocalcemia: Grade 4	3 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypocalcemia: Grades 1-4	48 participants	34 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypoglycemia: Grade 1	15 participants	10 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypoglycemia: Grade 2	1 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypoglycemia: Grade 3	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypoglycemia: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypoglycemia: Grades 1-4	16 participants	10 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypokalemia: Grade 1	18 participants	16 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypokalemia: Grade 2	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypokalemia: Grade 3	0 participants	1 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypokalemia: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hypokalemia: Grades 1-4	18 participants	17 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyponatremia: Grade 1	40 participants	28 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyponatremia: Grade 2	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyponatremia: Grade 3	0 participants	5 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyponatremia: Grade 4	0 participants	0 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Hyponatremia: Grades 1-4	40 participants	33 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Magnesium: Grade 1	46 participants	44 participants
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results Magnesium: Grade 2	0 participants	1 participants

SECONDARY outcome

Timeframe: 32 weeks (conducted at screening, Day 1 of each cycle, weekly during treatment, and at the end-of-treatment visit)

Population: Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen and who had an assessment.

Hematology test data were graded according to National Cancer Institute's (NCI) CTCAE version 3, and graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). The table presents the worst CTCAE grades for hematology test results experienced by participants overall (i.e., the worst post-baseline grade value for each participant and hematology test across all cycles).

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=221 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=215 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Absolute Neutrophil Count: Grade 1	22 participants	14 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Absolute Neutrophil Count: Grade 2	51 participants	20 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Absolute Neutrophil Count: Grade 3	48 participants	47 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Absolute Neutrophil Count: Grade 4	50 participants	104 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Absolute Neutrophil Count: Grades 1-4	171 participants	185 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Hemoglobin: Grade 1	129 participants	129 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Hemoglobin: Grade 2	42 participants	51 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Hemoglobin: Grade 3	5 participants	7 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Hemoglobin: Grade 4	1 participants	2 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Hemoglobin: Grades 1-4	177 participants	189 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Lymphocytes Absolute: Grade 1	1 participants	6 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Lymphocytes Absolute: Grade 2	5 participants	55 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Lymphocytes Absolute: Grade 3	54 participants	55 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Lymphocytes Absolute: Grade 4	83 participants	9 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Lymphocytes Absolute: Grades 1-4	143 participants	125 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Platelets: Grade 1	106 participants	72 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Platelets: Grade 2	14 participants	14 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Platelets: Grade 3	9 participants	7 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Platelets: Grade 4	7 participants	8 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results Platelets: Grades 1-4	136 participants	101 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results White Blood Cells: Grade 1	41 participants	22 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results White Blood Cells: Grade 2	79 participants	49 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results White Blood Cells: Grade 3	65 participants	89 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results White Blood Cells: Grade 4	19 participants	27 participants
Worst Overall CTCAE Grade for Hematology Laboratory Test Results White Blood Cells: Grades 1-4	204 participants	187 participants

SECONDARY outcome

Timeframe: 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)

Population: Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen and had baseline and post-baseline values.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=220 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=212 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Clinically Significant Abnormal Vital Signs Heart Rate >=120 and ↑ >=15 bpm	0 participants	1 participants
Clinically Significant Abnormal Vital Signs Heart Rate <=50 and ↓ >=15 bpm	2 participants	2 participants
Clinically Significant Abnormal Vital Signs Systolic Blood Pressure(BP) >=180 and ↑ >=20 mm Hg	2 participants	2 participants
Clinically Significant Abnormal Vital Signs Systolic BP <=90 and ↓ >=20 mm Hg	6 participants	2 participants
Clinically Significant Abnormal Vital Signs Diastolic BP >=105 and ↑ from Baseline >=15 mm Hg	1 participants	2 participants
Clinically Significant Abnormal Vital Signs Diastolic BP <=50 and ↓ from Baseline >=15 mm Hg	2 participants	2 participants

SECONDARY outcome

Timeframe: Baseline, Week 32

Population: Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen with a baseline and post-baseline weight.

Participants were weighed at Baseline and at Endpoint (Week 32); those participants with an increase or decrease of \>=10% were considered potentially clinically significant.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=220 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=212 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Potentially Clinically Significant Abnormal Weight Increase >=10%	8 participants	5 participants
Potentially Clinically Significant Abnormal Weight Decrease >=10%	18 participants	8 participants

SECONDARY outcome

Timeframe: Week 32

Population: Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen and with baseline and post-baseline values.

Participants' ECOG Performance Status was evaluated at the end of treatment as improved, stayed the same, or worsened from baseline (see Baseline Characteristics for ECOG Performance Status).

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=219 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=211 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period Improved	32 participants	28 participants
Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period Stayed the Same	153 participants	141 participants
Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period Worsened	34 participants	42 participants

SECONDARY outcome

Timeframe: prior to start of treatment

Population: Safety Analysis Set: all participants randomly assigned to a treatment group

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=224 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=223 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Therapeutic Classification of Prior Medications Psycholeptics	57 participants	59 participants
Therapeutic Classification of Prior Medications Sex Hormones and Modulators of the Genital System	11 participants	12 participants
Therapeutic Classification of Prior Medications Stomatological Preparations	0 participants	0 participants
Therapeutic Classification of Prior Medications Throat Preparations	0 participants	0 participants
Therapeutic Classification of Prior Medications Thyroid Therapy	16 participants	17 participants
Therapeutic Classification of Prior Medications Topical Products for Join and Muscular Pain	1 participants	0 participants
Therapeutic Classification of Prior Medications Unspecified Herbal	10 participants	10 participants
Therapeutic Classification of Prior Medications Urologicals	20 participants	11 participants
Therapeutic Classification of Prior Medications Vaccines	2 participants	7 participants
Therapeutic Classification of Prior Medications Vasoprotectives	0 participants	0 participants
Therapeutic Classification of Prior Medications Vitamins	70 participants	61 participants

SECONDARY outcome

Timeframe: 32 weeks

Population: Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=221 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=215 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Therapeutic Classification of Concomitant Medications Psycholeptics	69 participants	74 participants
Therapeutic Classification of Concomitant Medications Sex Hormones and Modulators of the Genital System	6 participants	4 participants
Therapeutic Classification of Concomitant Medications Stomatological Preparations	23 participants	29 participants
Therapeutic Classification of Concomitant Medications Throat Preparations	3 participants	2 participants
Therapeutic Classification of Concomitant Medications Thyroid Therapy	3 participants	1 participants
Therapeutic Classification of Concomitant Medications Topical Preparations for Join and Muscular Pain	1 participants	2 participants
Therapeutic Classification of Concomitant Medications Unspecified Herbal	3 participants	5 participants
Therapeutic Classification of Concomitant Medications Urologicals	5 participants	4 participants
Therapeutic Classification of Concomitant Medications Vaccines	11 participants	11 participants
Therapeutic Classification of Concomitant Medications Vasoprotectives	1 participants	8 participants
Therapeutic Classification of Concomitant Medications Vitamins	16 participants	21 participants

SECONDARY outcome

Timeframe: Day 1 (prior to treatment), 32 weeks

Population: The set of randomized participants (intent-to-treat) consisting of all patients randomly assigned to treatment, and who had data at both timepoints.

EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). This outcome reports the global health status on a scale of 0-100 with a high score for the global health status/QOL represents a high quality of life.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=211 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=207 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Change From Baseline to End of Treatment in the Global Health Status Score of the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ-C30)	3.6 units on a scale Standard Deviation 24.60	-5.1 units on a scale Standard Deviation 24.50

SECONDARY outcome

Timeframe: Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period

Population: Randomized patients: the set of randomized patients (intent-to-treat) consists of all patients randomly assigned to treatment.

Relapsed disease (after CR) and progressive disease (PD) (after PR or SD): * Lymph nodes were considered abnormal if the long axis was greater than 1.5 cm. Lymph nodes with a long axis of 1.1 to 1.5 cm were considered abnormal if its short axis was greater than 1.0 cm. * In patients with no prior history of pulmonary lymphoma, new lung nodules identified by CT require histologic confirmation. * \>= 50% increase from nadir in sum of the products of the greatest diameters (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules). To be considered progressive disease, a lymph node with a diameter of the short axis of less than 1.0 cm must have increased by 2: 50% and to a size of 1.5 cm by 1.5 cm, or more than 1.5 cm in the long axis * other conditions as specified in the protocol

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=224 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=223 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Participants With Disease Progression, Relapse or Death At the End of the Treatment Period or the Long-Term Follow-up Period	36 Participants	30 Participants

SECONDARY outcome

Timeframe: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

Population: Randomized patients

PFS was defined as the time from randomization to disease progression or relapse, or death from any cause, whichever occurred first.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=224 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=223 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Kaplan-Meier Estimate for Progression-free Survival (PFS)	31.8 months Interval 16.9 to 43.2	33.4 months Interval 19.3 to 48.7

SECONDARY outcome

Timeframe: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

Population: Randomized patients

EFS was defined as the time from randomization to treatment failure, disease progression or relapse, other malignancies, or death from any cause, whichever occurred first. Treatment failure was defined as failure to achieve a CR or PR after 6 cycles of treatment. If a patient failed to achieve CR or PR by the time of data analysis or early withdrawal, the treatment failure date was set at 126 days (6 cycles of treatment) after randomization or the new anticancer treatment date, whichever is earlier.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=224 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=223 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Kaplan-Meier Estimate for Event-free Survival (EFS)	31.8 months Interval 15.5 to 43.2	32.6 months Interval 18.1 to 44.7

SECONDARY outcome

Timeframe: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

Population: Randomized patients with complete response (CR) or partial response (PR)

DOR was defined as the time from first response (CR or PR) to disease progression or relapse, or death due to any cause.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=210 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=187 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Kaplan-Meier Estimate for Duration of Response (DOR)	26.5 months Interval 12.8 to 42.9	32.1 months Interval 19.8 to 46.7

SECONDARY outcome

Timeframe: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

Population: Randomized patients

OS was defined as the time from randomization to death from any cause.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=224 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=223 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Overall Survival (OS)	65.0 months Interval 64.8 to 65.1	64.1 months Interval 63.8 to 64.3

SECONDARY outcome

Timeframe: Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period

Population: Randomized patients: the set of randomized patients (intent-to-treat) consists of all patients randomly assigned to treatment.

Death is due to any cause. Data are broken out by patients who died within 30 days of the last dose of study medications, and those who died greater than 30 days of the last dose of study medications.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab (BR) n=224 Participants Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m\^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m\^2 IV on Day 1.	R-CHOP/R-CVP n=223 Participants Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m\^2 IV Day 1; cyclophosphamide 750 mg/m\^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m\^2 IV on Day 1; cyclophosphamide 750 mg/m\^2 IV on Day 1 or cyclophosphamide 1000 mg/m\^2 IV on Day 1; vincristine 1.4 mg/m\^2 (up to 2 mg/m\^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5
Participants Who Died At the End of the Treatment Period or the Long-Term Follow-up Period All Deaths	40 Participants	32 Participants
Participants Who Died At the End of the Treatment Period or the Long-Term Follow-up Period Deaths within 30 days of study treatment	2 Participants	1 Participants
Participants Who Died At the End of the Treatment Period or the Long-Term Follow-up Period Deaths greater than 30 days of study treatment	38 Participants	31 Participants

Adverse Events

Bendamustine and Rituximab (BR)

Serious events: 60 serious events

Other events: 216 other events

Deaths: 0 deaths

R-CHOP/CVP

Serious events: 49 serious events

Other events: 211 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Manager

Teva Pharmaceuticals USA

Phone: 1-866-384-5525

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator/Institution must submit proposed publication to Sponsor for review within a prespecified number of days before submission for publication. If Sponsor's review shows that potentially patentable subject matter would be disclosed, publication/public disclosure shall be delayed to enable Sponsor, or Sponsor's designees, to file necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER