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

• ClinicalTrials.gov Identifier: NCT00877006
• Recruitment Status: Completed
• First Posted: April 7, 2009
• Results First Posted: April 28, 2014
• Last Update Posted: February 5, 2018
• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Information provided by (Responsible Party): Teva Branded Pharmaceutical Products R&D, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Non-Hodgkin's Lymphoma; Mantle Cell Lymphoma
• Interventions: Drug: bendamustine; Drug: rituximab; Drug: vincristine; Drug: prednisone; Drug: cyclophosphamide; Drug: doxorubicin
• Enrollment: 447

Participant Flow

Recruitment Details
Pre-assignment Details	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).

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description	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.	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
Period Title: Treatment Period
Started	224	223
Completed	199	196
Not Completed	25	27
Reason Not Completed
Death	2	1
Adverse Event	10	3
Withdrawal by Subject	2	3
Protocol Violation	1	0
Lost to Follow-up	0	1
Disease Progression	1	2
Started New Treatment Regimen	2	5
Other	4	4
Randomized but Not Treated	3	8
Period Title: Long-Term Follow-up Period
Started	210	209
Completed	157	154
Not Completed	53	55
Reason Not Completed
Withdrawal by Subject	12	19
Lost to Follow-up	8	9
Death	26	18
Other	7	9

Baseline Characteristics

Arm/Group Title		Bendamustine and Rituximab (BR)	R-CHOP/R-CVP	Total
Arm/Group Description		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.	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 of all reporting groups
Overall Number of Baseline Participants		224	223	447
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	224 participants	223 participants	447 participants
		60.0 (11.37)	58.2 (12.11)	59.1 (11.77)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	224 participants	223 participants	447 participants
	Female	88 39.3%	91 40.8%	179 40.0%
	Male	136 60.7%	132 59.2%	268 60.0%
European Cooperative Oncology Group Performance Status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	224 participants	223 participants	447 participants
0		144	143	287
1		70	69	139
2		9	10	19
3		1	0	1
4		0	0	0
		[1] Measure Description: ECOG criteria: 0: Fully active. 1: Ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of all selfcare. 3: Capable of limited selfcare, confined to bed or chair more than 50% of waking hours. 4: Completely disabled, no selfcare, totally confined to bed or chair. 5: Dead. 1 participant in the R-CHOP/R-CVP treatment group did not have an assessment at baseline.
Weight [1]; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	224 participants	223 participants	447 participants
		81.9 (18.48)	82.4 (17.93)	82.1 (18.19)
		[1] Measure Description: one participant in the R-CHOP/R-CVP group did not a a weight measurement at baseline

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Complete Response (CR) at End of Treatment Period
Description	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.
Time Frame	6 to 8 21 or 28-day cycles (18-32 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	213	206
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	31; (25.3 to 38.2)	25; (19.5 to 31.7)

2. Secondary Outcome

Title	Percentage of Participants With Overall Response at End of Treatment Period
Description	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.
Time Frame	6 to 8 21 or 28-day cycles (18-32 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	213	206
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	97; (93.3 to 98.7)	91; (86.0 to 94.4)

3. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period
Description	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.
Time Frame	32 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	221	215
Measure Type: Number; Unit of Measure: participants
Any AE	221	213
Severe AEs (grades 3, 4, 5)	130	127
Treatment-related AEs	209	NA [1]
Deaths	12	9
SAEs	60	49
Withdrawn due to AEs	10	3

[1]

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.

4. Secondary Outcome

Title	Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results
Description	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).
Time Frame	32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	221	215
Measure Type: Number; Unit of Measure: participants
Albumin: Grade 1	33	44
Albumin: Grade 2	14	13
Albumin: Grade 3	3	0
Albumin: Grade 4	0	0
Albumin: Grades 1-4	50	57
Alkaline Phosphatase: Grade 1	41	25
Alkaline Phosphatase: Grade 2	1	3
Alkaline Phosphatase: Grade 3	0	0
Alkaline Phosphatase: Grade 4	0	0
Alkaline Phosphatase: Grades 1-4	42	28
Creatinine: Grade 1	19	25
Creatinine: Grade 2	3	1
Creatinine: Grade 3	1	0
Creatinine: Grade 4	0	0
Creatinine: Grades 1-4	23	26
Gamma-glutamyl transferase: Grade 1	31	37
Gamma-glutamyl transferase: Grade 2	18	10
Gamma-glutamyl transferase: Grade 3	3	6
Gamma-glutamyl transferase: Grade 4	0	0
Gamma-glutamyl transferase: Grades 1-4	52	53
Hypercalcemia: Grade 1	6	6
Hypercalcemia: Grade 2	0	0
Hypercalcemia: Grade 3	1	0
Hypercalcemia: Grade 4	0	0
Hypercalcemia: Grades 1-4	7	6
Hyperglycemia: Grade 1	94	74
Hyperglycemia: Grade 2	20	34
Hyperglycemia: Grade 3	15	15
Hyperglycemia: Grade 4	0	1
Hyperglycemia: Grades 1-4	129	124
Hyperkalemia: Grade 1	7	8
Hyperkalemia: Grade 2	3	1
Hyperkalemia: Grade 3	1	0
Hyperkalemia: Grade 4	0	0
Hyperkalemia: Grades 1-4	11	9
Hypernatremia: Grade 1	8	10
Hypernatremia: Grade 2	0	0
Hypernatremia: Grade 3	0	0
Hypernatremia: Grade 4	0	0
Hypernatremia: Grades 1-4	8	10
Hypocalcemia: Grade 1	36	28
Hypocalcemia: Grade 2	8	6
Hypocalcemia: Grade 3	1	0
Hypocalcemia: Grade 4	3	0
Hypocalcemia: Grades 1-4	48	34
Hypoglycemia: Grade 1	15	10
Hypoglycemia: Grade 2	1	0
Hypoglycemia: Grade 3	0	0
Hypoglycemia: Grade 4	0	0
Hypoglycemia: Grades 1-4	16	10
Hypokalemia: Grade 1	18	16
Hypokalemia: Grade 2	0	0
Hypokalemia: Grade 3	0	1
Hypokalemia: Grade 4	0	0
Hypokalemia: Grades 1-4	18	17
Hyponatremia: Grade 1	40	28
Hyponatremia: Grade 2	0	0
Hyponatremia: Grade 3	0	5
Hyponatremia: Grade 4	0	0
Hyponatremia: Grades 1-4	40	33
Magnesium: Grade 1	46	44
Magnesium: Grade 2	0	1
Magnesium: Grade 3	0	1
Magnesium: Grade 4	0	0
Magnesium: Grades 1-4	46	46
Phosphorus: Grade 1	7	5
Phosphorus: Grade 2	25	22
Phosphorus: Grade 3	3	3
Phosphorus: Grade 4	0	1
Phosphorus: Grades 1-4	35	31
Aspartate Aminotransferase: Grade 1	42	32
Aspartate Aminotransferase: Grade 2	2	2
Aspartate Aminotransferase: Grade 3	1	1
Aspartate Aminotransferase: Grade 4	0	0
Aspartate Aminotransferase: Grades 1-4	45	35
Alanine Aminotransferase: Grade 1	46	38
Alanine Aminotransferase: Grade 2	6	3
Alanine Aminotransferase: Grade 3	2	1
Alanine Aminotransferase: Grade 4	0	0
Alanine Aminotransferase: Grades 1-4	54	42
Total Bilirubin: Grade 1	14	7
Total Bilirubin: Grade 2	1	0
Total Bilirubin: Grade 3	0	0
Total Bilirubin: Grade 4	0	0
Total Bilirubin: Grades 1-4	15	7
Uric Acid: Grade 1	41	42
Uric Acid: Grade 2	0	0
Uric Acid: Grade 3	0	0
Uric Acid: Grade 4	1	0
Uric Acid: Grades 1-4	42	42

5. Secondary Outcome

Title	Worst Overall CTCAE Grade for Hematology Laboratory Test Results
Description	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).
Time Frame	32 weeks (conducted at screening, Day 1 of each cycle, weekly during treatment, and at the end-of-treatment visit)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	221	215
Measure Type: Number; Unit of Measure: participants
Absolute Neutrophil Count: Grade 1	22	14
Absolute Neutrophil Count: Grade 2	51	20
Absolute Neutrophil Count: Grade 3	48	47
Absolute Neutrophil Count: Grade 4	50	104
Absolute Neutrophil Count: Grades 1-4	171	185
Hemoglobin: Grade 1	129	129
Hemoglobin: Grade 2	42	51
Hemoglobin: Grade 3	5	7
Hemoglobin: Grade 4	1	2
Hemoglobin: Grades 1-4	177	189
Lymphocytes Absolute: Grade 1	1	6
Lymphocytes Absolute: Grade 2	5	55
Lymphocytes Absolute: Grade 3	54	55
Lymphocytes Absolute: Grade 4	83	9
Lymphocytes Absolute: Grades 1-4	143	125
Platelets: Grade 1	106	72
Platelets: Grade 2	14	14
Platelets: Grade 3	9	7
Platelets: Grade 4	7	8
Platelets: Grades 1-4	136	101
White Blood Cells: Grade 1	41	22
White Blood Cells: Grade 2	79	49
White Blood Cells: Grade 3	65	89
White Blood Cells: Grade 4	19	27
White Blood Cells: Grades 1-4	204	187

6. Secondary Outcome

Title	Clinically Significant Abnormal Vital Signs
Description	[Not Specified]
Time Frame	32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	220	212
Measure Type: Number; Unit of Measure: participants
Heart Rate >=120 and ↑ >=15 bpm	0	1
Heart Rate <=50 and ↓ >=15 bpm	2	2
Systolic Blood Pressure(BP) >=180 and ↑ >=20 mm Hg	2	2
Systolic BP <=90 and ↓ >=20 mm Hg	6	2
Diastolic BP >=105 and ↑ from Baseline >=15 mm Hg	1	2
Diastolic BP <=50 and ↓ from Baseline >=15 mm Hg	2	2

7. Secondary Outcome

Title	Potentially Clinically Significant Abnormal Weight
Description	Participants were weighed at Baseline and at Endpoint (Week 32); those participants with an increase or decrease of >=10% were considered potentially clinically significant.
Time Frame	Baseline, Week 32

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	220	212
Measure Type: Number; Unit of Measure: participants
Increase >=10%	8	5
Decrease >=10%	18	8

8. Secondary Outcome

Title	Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period
Description	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).
Time Frame	Week 32

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bendamustine/Rituximab	R-CHOP/R-CVP
Arm/Group Description:	bendamustine at 90 mg/m2 iv on days 1 and 2 and rituximab at 375 mg/m2 iv infusion on day 1	R-CHOP, consisting of rituximab at 375 mg/m2 iv on day 1, vincristine at 1.4 mg /m2 (up to a maximum dose of 2 mg iv) by iv on day 1, prednisone at 100 mg orally on days 1 to 5 of a 21-day cycle, doxorubicin at 50 mg/m2 by iv over 3-5 minutes on day 1, cyclophosphamide iv at 750 mg/m2 on day 1. R-CVP consisting of rituximab at 375 mg/m2 iv on day 1, vincristine at 1.4 mg /m2 (up to a maximum dose of 2 mg iv) by iv on day 1, prednisone at 100 mg orally on days 1 to 5 of a 21-day cycle, only 1 of the following doses of cyclophosphamide throughout the study: cyclophosphamide at 750 mg/m2 iv on day 1 or cyclophosphamide at 1000 mg/m2 iv on day 1.
Overall Number of Participants Analyzed	219	211
Measure Type: Number; Unit of Measure: participants
Improved	32	28
Stayed the Same	153	141
Worsened	34	42

9. Secondary Outcome

Title	Therapeutic Classification of Prior Medications
Description	[Not Specified]
Time Frame	prior to start of treatment

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	224	223
Measure Type: Number; Unit of Measure: participants
Psycholeptics	57	59
Sex Hormones and Modulators of the Genital System	11	12
Stomatological Preparations	0	0
Throat Preparations	0	0
Thyroid Therapy	16	17
Topical Products for Join and Muscular Pain	1	0
Unspecified Herbal	10	10
Urologicals	20	11
Vaccines	2	7
Vasoprotectives	0	0
Vitamins	70	61

10. Secondary Outcome

Title	Therapeutic Classification of Concomitant Medications
Description	[Not Specified]
Time Frame	32 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	221	215
Measure Type: Number; Unit of Measure: participants
Psycholeptics	69	74
Sex Hormones and Modulators of the Genital System	6	4
Stomatological Preparations	23	29
Throat Preparations	3	2
Thyroid Therapy	3	1
Topical Preparations for Join and Muscular Pain	1	2
Unspecified Herbal	3	5
Urologicals	5	4
Vaccines	11	11
Vasoprotectives	1	8
Vitamins	16	21

11. Secondary Outcome

Title	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)
Description	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.
Time Frame	Day 1 (prior to treatment), 32 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	211	207
Mean (Standard Deviation); Unit of Measure: units on a scale
	3.6 (24.60)	-5.1 (24.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine and Rituximab (BR), R-CHOP/R-CVP
	Comments	The hypothesis of interest is superiority of BR over standard treatment.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0005
	Comments	P-value for the treatment comparison is from an analysis of covariance (ANCOVA) with treatment group, region, preassigned standard treatment, and lymphoma type as factors and baseline value as the covariate.
	Method	ANCOVA
	Comments	[Not Specified]

12. Secondary Outcome

Title	Participants With Disease Progression, Relapse or Death At the End of the Treatment Period or the Long-Term Follow-up Period
Description	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
Time Frame	Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	224	223
Measure Type: Count of Participants; Unit of Measure: Participants
	36 16.1%	30 13.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine and Rituximab (BR), R-CHOP/R-CVP
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9677
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified log-rank test by preassigned standard treatment and lymphoma type.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.58 to 1.68
	Estimation Comments	BR/RCHOP-RCVP

13. Secondary Outcome

Title	Kaplan-Meier Estimate for Progression-free Survival (PFS)
Description	PFS was defined as the time from randomization to disease progression or relapse, or death from any cause, whichever occurred first.
Time Frame	Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

Outcome Measure Data

Analysis Population Description

Randomized patients

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	224	223
Median (95% Confidence Interval); Unit of Measure: months
	31.8; (16.9 to 43.2)	33.4; (19.3 to 48.7)

14. Secondary Outcome

Title	Kaplan-Meier Estimate for Event-free Survival (EFS)
Description	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.
Time Frame	Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

Outcome Measure Data

Analysis Population Description

Randomized patients

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	224	223
Median (95% Confidence Interval); Unit of Measure: months
	31.8; (15.5 to 43.2)	32.6; (18.1 to 44.7)

15. Secondary Outcome

Title	Kaplan-Meier Estimate for Duration of Response (DOR)
Description	DOR was defined as the time from first response (CR or PR) to disease progression or relapse, or death due to any cause.
Time Frame	Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	210	187
Median (95% Confidence Interval); Unit of Measure: months
	26.5; (12.8 to 42.9)	32.1; (19.8 to 46.7)

16. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to death from any cause.
Time Frame	Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

Outcome Measure Data

Analysis Population Description

Randomized patients

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	224	223
Median (95% Confidence Interval); Unit of Measure: months
	65.0; (64.8 to 65.1)	64.1; (63.8 to 64.3)

17. Secondary Outcome

Title	Participants Who Died At the End of the Treatment Period or the Long-Term Follow-up Period
Description	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.
Time Frame	Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bendamustine and Rituximab (BR)	R-CHOP/R-CVP
Arm/Group Description:	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.	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 Number of Participants Analyzed	224	223
Measure Type: Count of Participants; Unit of Measure: Participants
All Deaths	40 17.9%	32 14.3%
Deaths within 30 days of study treatment	2 0.9%	1 0.4%
Deaths greater than 30 days of study treatment	38 17.0%	31 13.9%

Adverse Events

Time Frame	Treatment Period: 32 weeks No adverse event data was collected during the 5-year Long-Term Follow-Up Period
Adverse Event Reporting Description	Events are reported for the safety analysis set (participants who received at least 1 dose of study drug).
Arm/Group Title	Bendamustine and Rituximab (BR)		R-CHOP/CVP
Arm/Group Description	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.		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
All-Cause Mortality
	Bendamustine and Rituximab (BR)		R-CHOP/CVP
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Bendamustine and Rituximab (BR)		R-CHOP/CVP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/221 (27.15%)		49/215 (22.79%)
Blood and lymphatic system disorders
Aplasia pure red cell † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Febrile neutropenia † 1	7/221 (3.17%)	8	9/215 (4.19%)	10
Lymphadenopathy † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Neutropenia † 1	4/221 (1.81%)	6	5/215 (2.33%)	6
Splenomegaly † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Cardiac disorders
Atrial fibrillation † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Atrioventricular block first degree † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Bundle branch block left † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Cardiac arrest † 1	1/221 (0.45%)	1	1/215 (0.47%)	1
Cardiac failure congestive † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Left ventricular dysfunction † 1	1/221 (0.45%)	1	1/215 (0.47%)	2
Myocardial infarction † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Pericardial effusion † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Supraventricular tachycardia † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Eye disorders
Vitreous floaters † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	2/221 (0.90%)	3	1/215 (0.47%)	1
Ascites † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Constipation † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Diarrhoea † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Diverticular perforation † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Gastrooesophageal reflux disease † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Ileus † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Nausea † 1	3/221 (1.36%)	3	0/215 (0.00%)	0
Rectal haemorrhage † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Small intestinal obstruction † 1	1/221 (0.45%)	1	1/215 (0.47%)	1
Vomiting † 1	3/221 (1.36%)	3	0/215 (0.00%)	0
General disorders
Chills † 1	1/221 (0.45%)	2	0/215 (0.00%)	0
Non-cardiac chest pain † 1	0/221 (0.00%)	0	3/215 (1.40%)	3
Pyrexia † 1	5/221 (2.26%)	6	4/215 (1.86%)	5
Hepatobiliary disorders
Cholelithiasis † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Portal vein thrombosis † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Immune system disorders
Anaphylactic shock † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Drug hypersensitivity † 1	4/221 (1.81%)	4	0/215 (0.00%)	0
Infections and infestations
Abscess limb † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Anal infection † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Bacteraemia † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Clostridium difficile colitis † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Diverticulitis † 1	2/221 (0.90%)	3	1/215 (0.47%)	1
Gastroenteritis † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Gastrointestinal infection † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Infection † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Infective exacerbation of chronic obstructive airways disease † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Lower respiratory tract infection † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Pharyngitis † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Pneumocystis jiroveci infection † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Pneumocystis jiroveci pneumonia † 1	1/221 (0.45%)	1	1/215 (0.47%)	1
Pneumonia † 1	7/221 (3.17%)	7	1/215 (0.47%)	1
Postoperative wound infection † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Septic shock † 1	1/221 (0.45%)	1	1/215 (0.47%)	2
Tooth abscess † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Tooth infection † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Tracheobronchitis † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Upper respiratory tract infection † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Urinary tract infection † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Viral infection † 1	2/221 (0.90%)	2	0/215 (0.00%)	0
Injury, poisoning and procedural complications
Ankle fracture † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Cervical vertebral fracture † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Clavicle fracture † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Fall † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Infusion related reaction † 1	8/221 (3.62%)	11	4/215 (1.86%)	4
Procedural complication † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Rib fracture † 1	1/221 (0.45%)	1	1/215 (0.47%)	1
Spinal compression fracture † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Toxicity to various agents † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Investigations
Electrocardiogram QT prolonged † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Metabolism and nutrition disorders
Dehydration † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Hyperglycaemia † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Tumour lysis syndrome † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	0/221 (0.00%)	0	2/215 (0.93%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant † 1	1/221 (0.45%)	2	0/215 (0.00%)	0
Renal cell carcinoma † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Sarcoma † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Nervous system disorders
Dystonia † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Headache † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Intracranial aneurysm † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Neuropathy peripheral † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Syncope † 1	1/221 (0.45%)	1	1/215 (0.47%)	1
Psychiatric disorders
Confusional state † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Depression † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Renal and urinary disorders
Haematuria † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Renal failure acute † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Renal tubular necrosis † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Urinary retention † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Reproductive system and breast disorders
Prostatitis † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Chronic obstructive pulmonary disease † 1	2/221 (0.90%)	3	0/215 (0.00%)	0
Dyspnoea † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Hypoxia † 1	1/221 (0.45%)	1	1/215 (0.47%)	1
Interstitial lung disease † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Pleural effusion † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Pulmonary embolism † 1	1/221 (0.45%)	1	1/215 (0.47%)	1
Respiratory failure † 1	2/221 (0.90%)	2	0/215 (0.00%)	0
Skin and subcutaneous tissue disorders
Rash † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
Rash maculo-papular † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Vascular disorders
Hypertension † 1	0/221 (0.00%)	0	1/215 (0.47%)	1
Hypotension † 1	1/221 (0.45%)	1	0/215 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Bendamustine and Rituximab (BR)		R-CHOP/CVP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	216/221 (97.74%)		211/215 (98.14%)
Blood and lymphatic system disorders
Anaemia † 1	31/221 (14.03%)	63	29/215 (13.49%)	69
Febrile neutropenia † 1	7/221 (3.17%)	9	11/215 (5.12%)	12
Leukopenia † 1	21/221 (9.50%)	79	22/215 (10.23%)	88
Lymphopenia † 1	14/221 (6.33%)	104	12/215 (5.58%)	44
Neutropenia † 1	76/221 (34.39%)	251	85/215 (39.53%)	255
Thrombocytopenia † 1	29/221 (13.12%)	67	13/215 (6.05%)	54
Gastrointestinal disorders
Abdominal pain † 1	25/221 (11.31%)	33	27/215 (12.56%)	31
Abdominal pain upper † 1	11/221 (4.98%)	11	14/215 (6.51%)	16
Constipation † 1	65/221 (29.41%)	85	90/215 (41.86%)	121
Diarrhoea † 1	46/221 (20.81%)	65	50/215 (23.26%)	72
Dyspepsia † 1	23/221 (10.41%)	23	26/215 (12.09%)	29
Gastrooesophageal reflux disease † 1	16/221 (7.24%)	16	17/215 (7.91%)	18
Nausea † 1	139/221 (62.90%)	255	102/215 (47.44%)	139
Stomatitis † 1	15/221 (6.79%)	20	14/215 (6.51%)	17
Vomiting † 1	60/221 (27.15%)	86	28/215 (13.02%)	35
General disorders
Asthenia † 1	14/221 (6.33%)	16	17/215 (7.91%)	24
Chest discomfort † 1	8/221 (3.62%)	10	13/215 (6.05%)	14
Chills † 1	25/221 (11.31%)	34	11/215 (5.12%)	14
Fatigue † 1	113/221 (51.13%)	179	107/215 (49.77%)	147
Mucosal inflammation † 1	12/221 (5.43%)	15	26/215 (12.09%)	36
Oedema peripheral † 1	19/221 (8.60%)	23	23/215 (10.70%)	27
Pain † 1	14/221 (6.33%)	15	14/215 (6.51%)	17
Pyrexia † 1	37/221 (16.74%)	45	28/215 (13.02%)	31
Immune system disorders
Drug hypersensitivity † 1	24/221 (10.86%)	32	8/215 (3.72%)	9
Infections and infestations
Nasopharyngitis † 1	9/221 (4.07%)	9	11/215 (5.12%)	11
Sinusitis † 1	5/221 (2.26%)	7	12/215 (5.58%)	14
Upper respiratory tract infection † 1	22/221 (9.95%)	26	17/215 (7.91%)	20
Injury, poisoning and procedural complications
Infusion related reaction † 1	52/221 (23.53%)	115	45/215 (20.93%)	64
Investigations
Neutrophil count decreased † 1	9/221 (4.07%)	15	12/215 (5.58%)	18
Weight decreased † 1	14/221 (6.33%)	14	7/215 (3.26%)	8
Metabolism and nutrition disorders
Decreased appetite † 1	42/221 (19.00%)	57	26/215 (12.09%)	26
Hyperglycaemia † 1	4/221 (1.81%)	9	11/215 (5.12%)	26
Musculoskeletal and connective tissue disorders
Arthralgia † 1	28/221 (12.67%)	33	32/215 (14.88%)	46
Back pain † 1	23/221 (10.41%)	26	27/215 (12.56%)	39
Bone pain † 1	9/221 (4.07%)	10	18/215 (8.37%)	20
Muscle spasms † 1	6/221 (2.71%)	6	11/215 (5.12%)	14
Musculoskeletal pain † 1	12/221 (5.43%)	12	17/215 (7.91%)	18
Myalgia † 1	13/221 (5.88%)	15	18/215 (8.37%)	21
Pain in extremity † 1	17/221 (7.69%)	23	18/215 (8.37%)	20
Nervous system disorders
Dizziness † 1	18/221 (8.14%)	31	21/215 (9.77%)	29
Dysgeusia † 1	28/221 (12.67%)	32	25/215 (11.63%)	25
Headache † 1	48/221 (21.72%)	60	45/215 (20.93%)	68
Neuropathy peripheral † 1	9/221 (4.07%)	13	51/215 (23.72%)	77
Paraesthesia † 1	7/221 (3.17%)	8	25/215 (11.63%)	29
Peripheral sensory neuropathy † 1	4/221 (1.81%)	4	20/215 (9.30%)	24
Psychiatric disorders
Anxiety † 1	17/221 (7.69%)	18	18/215 (8.37%)	20
Insomnia † 1	37/221 (16.74%)	42	47/215 (21.86%)	53
Respiratory, thoracic and mediastinal disorders
Cough † 1	34/221 (15.38%)	37	34/215 (15.81%)	36
Dyspnoea † 1	17/221 (7.69%)	23	26/215 (12.09%)	28
Oropharyngeal pain † 1	18/221 (8.14%)	20	16/215 (7.44%)	18
Skin and subcutaneous tissue disorders
Alopecia † 1	8/221 (3.62%)	8	74/215 (34.42%)	83
Dry skin † 1	12/221 (5.43%)	13	7/215 (3.26%)	7
Night sweats † 1	7/221 (3.17%)	7	15/215 (6.98%)	15
Pruritus † 1	22/221 (9.95%)	26	10/215 (4.65%)	10
Rash † 1	33/221 (14.93%)	40	17/215 (7.91%)	20
Vascular disorders
Hypotension † 1	12/221 (5.43%)	13	7/215 (3.26%)	8
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Manager
• Organization: Teva Pharmaceuticals USA
• Phone: 1-866-384-5525
• EMail: clinicaltrialqueries@tevausa.com

Publications of Results:

Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. doi: 10.1182/blood-2013-11-531327. Epub 2014 Mar 3.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-Line Treatment of Patients With Indolent Non-Hodgkin Lymphoma or Mantle-Cell Lymphoma With Bendamustine Plus Rituximab Versus R-CHOP or R-CVP: Results of the BRIGHT 5-Year Follow-Up Study. J Clin Oncol. 2019 Apr 20;37(12):984-991. doi: 10.1200/JCO.18.00605. Epub 2019 Feb 27.

Burke JM, van der Jagt RH, Kahl BS, Wood P, Hawkins TE, MacDonald D, Hertzberg M, Simpson D, Craig M, Kolibaba K, Issa S, Munteanu M, Victor TW, Flinn IW. Differences in Quality of Life Between Bendamustine-Rituximab and R-CHOP/R-CVP in Patients With Previously Untreated Advanced Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2016 Apr;16(4):182-190.e1. doi: 10.1016/j.clml.2016.01.001. Epub 2016 Jan 15.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT00877006
• Other Study ID Numbers: C18083/3064/NL/MN
• First Submitted: April 3, 2009
• First Posted: April 7, 2009
• Results First Submitted: March 25, 2014
• Results First Posted: April 28, 2014
• Last Update Posted: February 5, 2018