Study of Bendamustine Hydrochloride and Rituximab (BR) Co... | NCT00877006

NCT00877006

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Bendamustine and Rituximab (BR)	Experimental	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	Drug: bendamustine Drug: rituximab
R-CHOP/R-CVP	Active Comparator	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	Drug: rituximab Drug: vincristine Drug: prednisone Drug: cyclophosphamide Drug: doxorubicin

Name	Type	Description	Arm Group Labels	Other Names
bendamustine	Drug		Bendamustine and Rituximab (BR)	Treakisym Ribomustin Levact Treanda

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Overall Response at End of Treatment Period	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.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Histopathologic confirmation of one of the following cluster of differentiation antigen 20 positive (CD20+) B-cell non-Hodgkin's lymphomas (tissue diagnostic procedures must be performed within 6 months of study entry and with biopsy material available for review):
- follicular lymphoma (NCI CTCAE grade 1 or 2)
- immunoplasmacytoma/immunocytoma (Waldenstrom's macroglobulinemia)
- splenic marginal zone B-cell lymphoma
- extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tumor (MALT) type
- nodal marginal zone B-cell lymphoma
- mantle cell lymphoma
Meets one of the following need-for-treatment criteria (with the exception of mantle cell lymphoma for which treatment is indicated):
- presence of at least one of the following B-symptoms:
  1. fever (>38ºC) of unclear etiology
  2. night sweats
  3. weight loss of greater than 10% within the prior 6 months
- large tumor mass (bulky disease)
- presence of lymphoma-related complications, including narrowing of ureters or bile ducts, tumor-related compression of a vital organ, lymphoma-induced pain, cytopenias related to lymphoma/leukemia, splenomegaly, pleural effusions, or ascites
- hyperviscosity syndrome due to monoclonal gammopathy
CD20+ B cells in lymph node biopsy or other lymphoma pathology specimen.
No prior treatment (patients on "watch and wait" may enter the study if a recent biopsy [obtained within the last 6 months] is available)
Adequate hematologic function (unless abnormalities related to lymphoma infiltration of the bone marrow or hypersplenism due to lymphoma) as follows:
- hemoglobin of >= 10.0 g/dL
- absolute neutrophil count (ANC) >=1.5*10^9/L
- platelet count >=100*10^9/L
Bidimensionally measurable disease (field not previously radiated)
Able to provide written informed consent
Eastern Cooperative Oncology Group (ECOG) Performance Status <=2
Estimated life expectancy >=6 months
Serum creatinine of <=2.0 mg/dL or creatinine clearance >=50 mL/min
Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤2.5*upper limit of normal (ULN), and alkaline phosphatase and total bilirubin within normal limits
Left ventricular ejection fraction (LVEF) >= 50% by multiple gated acquisition scan (MUGA) or cardiac echocardiogram (ECHO), prior for any patient to be treated with R-CHOP
A medically accepted method of contraception to be used by women of childbearing potential (not surgically sterile or at least 12 months naturally postmenopausal)
Men capable of producing offspring and not surgically sterile must practice abstinence or use a barrier method of birth control.

Key Exclusion Criteria:

Chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL), or grade 3 follicular lymphoma
Transformed disease (bone marrow blasts are permitted; however, transformed disease indicating leukemic involvement is not permitted)
Central nervous system (CNS) lymphomatous involvement or leptomeningeal lymphoma
Prior radiation for NHL, except for a single course of locally delimited radiation therapy with a radiation field not exceeding 2 adjacent lymph node regions
Active malignancy, other than NHL, within the past 3 years except for localized prostate cancer treated with hormone therapy, cervical carcinoma in situ, breast cancer in situ, or non-melanoma skin cancer following definitive treatment
New York Heart Association (NYHA) Class III or IV heart failure, arrhythmias or unstable angina, electrocardiograph (ECG) evidence of active ischemia or active conduction system abnormalities, or myocardial infarction within the last 6 months (prior to study entry, ECG abnormalities at screening must be documented by the investigator as not medically relevant)
Known human immunodeficiency virus (HIV) positivity
Active hepatitis B or hepatitis C infection (hepatitis B surface antigen testing required)
Women who are pregnant or lactating
Corticosteroids for treatment of lymphoma within 28 days of study entry Chronically administered low-dose corticosteroids (e.g., prednisone ≤20 mg/day) for indications other than lymphoma or lymphoma-related complications are permitted
Any serious uncontrolled, medical or psychological disorder that would impair the ability of the patient to receive therapy
Any condition which places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data
Any other investigational agent within 28 days of study entry
Known hypersensitivity to bendamustine, mannitol, or other study-related drugs
Ann Arbor stage I disease.

Name	Affiliation	Role
Sponsor's Medical Expert	Cephalon	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Teva Investigational Site 165		Tucson	Arizona		United States
Teva Investigational Site 167

PubMed Identifier	Type	Citation	Retractions
24591201	Result	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.
30811293

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	R-CHOP/R-CVP

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00060.0± 11.37 BG00158.2± 12.11 BG00259.1± 11.77

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00088 BG00191 BG002

European Cooperative Oncology Group Performance Status

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.

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG000144 BG001

Weight

one participant in the R-CHOP/R-CVP group did not a a weight measurement at baseline

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00081.9± 18.48 BG00182.4± 17.93

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Complete Response (CR) at End of Treatment Period

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.

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.

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	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.
OG001	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

Units	Counts
Participants	OG000213 OG001206

Title

Denominators

Categories

Title	Measurements
	OG00031(25.3 to 38.2) OG00125(19.5 to 31.7)

Secondary

Percentage of Participants With Overall Response at End of Treatment Period

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.

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	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.
OG001	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

Secondary

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period

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.

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.

Posted

Number

participants

32 weeks

ID	Title	Description
OG000	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.
OG001	R-CHOP/R-CVP

Secondary

Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results

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).

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.

Posted

Number

participants

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

ID	Title	Description
OG000	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.
OG001	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

Secondary

Worst Overall CTCAE Grade for Hematology Laboratory Test Results

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).

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.

Posted

Number

participants

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

ID	Title	Description
OG000	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.
OG001	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

Secondary

Clinically Significant Abnormal Vital Signs

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.

Posted

Number

participants

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

ID	Title	Description
OG000	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.
OG001	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

Units	Counts

Secondary

Potentially Clinically Significant Abnormal 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.

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.

Posted

Number

participants

Baseline, Week 32

ID	Title	Description
OG000	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.
OG001	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

Secondary

Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period

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).

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.

Posted

Number

participants

Week 32

ID	Title	Description
OG000	Bendamustine/Rituximab	bendamustine at 90 mg/m2 iv on days 1 and 2 and rituximab at 375 mg/m2 iv infusion on day 1
OG001	R-CHOP/R-CVP	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.

Secondary

Therapeutic Classification of Prior Medications

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

Posted

Number

participants

prior to start of treatment

ID	Title	Description
OG000	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.
OG001	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

Units	Counts
Participants

Secondary

Therapeutic Classification of Concomitant Medications

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.

Posted

Number

participants

32 weeks

ID	Title	Description
OG000	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.
OG001	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

Units	Counts
Participants

Secondary

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)

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.

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

Posted

Mean

Standard Deviation

units on a scale

Day 1 (prior to treatment), 32 weeks

ID	Title	Description
OG000	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.
OG001	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

Secondary

Participants With Disease Progression, Relapse or Death At the End of the Treatment Period or the Long-Term Follow-up Period

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

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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.
OG001	R-CHOP/R-CVP

Secondary

Kaplan-Meier Estimate for Progression-free Survival (PFS)

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

Randomized patients

Posted

Median

95% Confidence Interval

months

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

ID	Title	Description
OG000	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.
OG001	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

Units	Counts

Secondary

Kaplan-Meier Estimate for Event-free Survival (EFS)

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.

Randomized patients

Posted

Median

95% Confidence Interval

months

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

ID	Title	Description
OG000	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.
OG001	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

Secondary

Kaplan-Meier Estimate for Duration of Response (DOR)

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

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

Posted

Median

95% Confidence Interval

months

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

ID	Title	Description
OG000	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.
OG001	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

Units

Secondary

Overall Survival (OS)

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

Randomized patients

Posted

Median

95% Confidence Interval

months

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

ID	Title	Description
OG000	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.
OG001	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

Units	Counts
Participants

Secondary

Participants Who Died At the End of the Treatment Period or the Long-Term Follow-up Period

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.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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.
OG001	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

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Aplasia pure red cell	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0008 events7 affected221 at risk EG00110 events9 affected215 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0006 events4 affected221 at risk EG0016 events5 affected215 at risk
Splenomegaly	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Atrioventricular block first degree	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Bundle branch block left	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Cardiac arrest	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0011 events1 affected215 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0012 events1 affected215 at risk
Myocardial infarction	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Pericardial effusion	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Vitreous floaters	Eye disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0003 events2 affected221 at risk EG0011 events1 affected215 at risk
Ascites	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Constipation	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Diverticular perforation	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Ileus	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Nausea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0003 events3 affected221 at risk EG0010 events0 affected215 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0011 events1 affected215 at risk
Vomiting	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0003 events3 affected221 at risk EG0010 events0 affected215 at risk
Chills	General disorders	MedDRA 15.0	Systematic Assessment	EG0002 events1 affected221 at risk EG0010 events0 affected215 at risk
Non-cardiac chest pain	General disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0013 events3 affected215 at risk
Pyrexia	General disorders	MedDRA 15.0	Systematic Assessment	EG0006 events5 affected221 at risk EG0015 events4 affected215 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Anaphylactic shock	Immune system disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 15.0	Systematic Assessment	EG0004 events4 affected221 at risk EG0010 events0 affected215 at risk
Abscess limb	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Anal infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Bacteraemia	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Diverticulitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0003 events2 affected221 at risk EG0011 events1 affected215 at risk
Gastroenteritis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Pharyngitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Pneumocystis jiroveci infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Pneumocystis jiroveci pneumonia	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0011 events1 affected215 at risk
Pneumonia	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0007 events7 affected221 at risk EG0011 events1 affected215 at risk
Postoperative wound infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Septic shock	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0012 events1 affected215 at risk
Tooth abscess	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Tooth infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Tracheobronchitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Urinary tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Viral infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0002 events2 affected221 at risk EG0010 events0 affected215 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG00011 events8 affected221 at risk EG0014 events4 affected215 at risk
Procedural complication	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0011 events1 affected215 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Tumour lysis syndrome	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0013 events2 affected215 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0002 events1 affected221 at risk EG0010 events0 affected215 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Sarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Dystonia	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Headache	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Intracranial aneurysm	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Syncope	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0011 events1 affected215 at risk
Confusional state	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Depression	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Haematuria	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Renal tubular necrosis	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Urinary retention	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0003 events2 affected221 at risk EG0010 events0 affected215 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0011 events1 affected215 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0011 events1 affected215 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0002 events2 affected221 at risk EG0010 events0 affected215 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Hypertension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected221 at risk EG0011 events1 affected215 at risk
Hypotension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected221 at risk EG0010 events0 affected215 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG00063 events31 affected221 at risk EG00169 events29 affected215 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0009 events7 affected221 at risk EG00112 events11 affected215 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG00079 events21 affected221 at risk EG00188 events22 affected215 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG000104 events14 affected221 at risk EG00144 events12 affected215 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG000251 events76 affected221 at risk EG001255 events85 affected215 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG00067 events29 affected221 at risk EG00154 events13 affected215 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00033 events25 affected221 at risk EG00131 events27 affected215 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00011 events11 affected221 at risk EG00116 events14 affected215 at risk
Constipation	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00085 events65 affected221 at risk EG001121 events90 affected215 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00065 events46 affected221 at risk EG00172 events50 affected215 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00023 events23 affected221 at risk EG00129 events26 affected215 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00016 events16 affected221 at risk EG00118 events17 affected215 at risk
Nausea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG000255 events139 affected221 at risk EG001139 events102 affected215 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00020 events15 affected221 at risk EG00117 events14 affected215 at risk
Vomiting	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00086 events60 affected221 at risk EG00135 events28 affected215 at risk
Asthenia	General disorders	MedDRA 15.0	Systematic Assessment	EG00016 events14 affected221 at risk EG00124 events17 affected215 at risk
Chest discomfort	General disorders	MedDRA 15.0	Systematic Assessment	EG00010 events8 affected221 at risk EG00114 events13 affected215 at risk
Chills	General disorders	MedDRA 15.0	Systematic Assessment	EG00034 events25 affected221 at risk EG00114 events11 affected215 at risk
Fatigue	General disorders	MedDRA 15.0	Systematic Assessment	EG000179 events113 affected221 at risk EG001147 events107 affected215 at risk
Mucosal inflammation	General disorders	MedDRA 15.0	Systematic Assessment	EG00015 events12 affected221 at risk EG00136 events26 affected215 at risk
Oedema peripheral	General disorders	MedDRA 15.0	Systematic Assessment	EG00023 events19 affected221 at risk EG00127 events23 affected215 at risk
Pain	General disorders	MedDRA 15.0	Systematic Assessment	EG00015 events14 affected221 at risk EG00117 events14 affected215 at risk
Pyrexia	General disorders	MedDRA 15.0	Systematic Assessment	EG00045 events37 affected221 at risk EG00131 events28 affected215 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 15.0	Systematic Assessment	EG00032 events24 affected221 at risk EG0019 events8 affected215 at risk
Nasopharyngitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0009 events9 affected221 at risk EG00111 events11 affected215 at risk
Sinusitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0007 events5 affected221 at risk EG00114 events12 affected215 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00026 events22 affected221 at risk EG00120 events17 affected215 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG000115 events52 affected221 at risk EG00164 events45 affected215 at risk
Neutrophil count decreased	Investigations	MedDRA 15.0	Systematic Assessment	EG00015 events9 affected221 at risk EG00118 events12 affected215 at risk
Weight decreased	Investigations	MedDRA 15.0	Systematic Assessment	EG00014 events14 affected221 at risk EG0018 events7 affected215 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG00057 events42 affected221 at risk EG00126 events26 affected215 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0009 events4 affected221 at risk EG00126 events11 affected215 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG00033 events28 affected221 at risk EG00146 events32 affected215 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG00026 events23 affected221 at risk EG00139 events27 affected215 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG00010 events9 affected221 at risk EG00120 events18 affected215 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0006 events6 affected221 at risk EG00114 events11 affected215 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG00012 events12 affected221 at risk EG00118 events17 affected215 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG00015 events13 affected221 at risk EG00121 events18 affected215 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG00023 events17 affected221 at risk EG00120 events18 affected215 at risk
Dizziness	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG00031 events18 affected221 at risk EG00129 events21 affected215 at risk
Dysgeusia	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG00032 events28 affected221 at risk EG00125 events25 affected215 at risk
Headache	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG00060 events48 affected221 at risk EG00168 events45 affected215 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG00013 events9 affected221 at risk EG00177 events51 affected215 at risk
Paraesthesia	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0008 events7 affected221 at risk EG00129 events25 affected215 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0004 events4 affected221 at risk EG00124 events20 affected215 at risk
Anxiety	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG00018 events17 affected221 at risk EG00120 events18 affected215 at risk
Insomnia	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG00042 events37 affected221 at risk EG00153 events47 affected215 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG00037 events34 affected221 at risk EG00136 events34 affected215 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG00023 events17 affected221 at risk EG00128 events26 affected215 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG00020 events18 affected221 at risk EG00118 events16 affected215 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0008 events8 affected221 at risk EG00183 events74 affected215 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG00013 events12 affected221 at risk EG0017 events7 affected215 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0007 events7 affected221 at risk EG00115 events15 affected215 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG00026 events22 affected221 at risk EG00110 events10 affected215 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG00040 events33 affected221 at risk EG00120 events17 affected215 at risk
Hypotension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG00013 events12 affected221 at risk EG0018 events7 affected215 at risk

Ancestor Terms

ID	Term
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D001562	Benzimidazoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D014748	Vinca Alkaloids
D046948	Secologanin Tryptamine Alkaloids
D026121	Indole Alkaloids
D000470	Alkaloids
D007211	Indoles
D054836	Indolizidines
D007212	Indolizines
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D010752	Phosphoramide Mustards
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates

ID	Term
D008228	Lymphoma, Non-Hodgkin
D020522	Lymphoma, Mantle-Cell

ID	Term
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D000069461	Bendamustine Hydrochloride
D000069283	Rituximab
D014750	Vincristine
D011241	Prednisone
D003520	Cyclophosphamide
D004317	Doxorubicin

ID	Title	Description
BG000	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.
BG001	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
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.			60	221	216	221
EG001	R-CHOP/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			49	215	211	215