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

Sponsor
Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00877006
Collaborator
(none)
447
128
2
35
3.5
0.1

Study Details

Study Description

Brief Summary

The primary objective of the study is to compare the complete response (CR) rate of bendamustine and rituximab (BR) with that of standard treatment regimens of either rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with advanced, indolent non-Hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL).

Study Design

Study Type:
Interventional
Actual Enrollment :
447 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Randomized, Parallel-Group Study of Bendamustine Hydrochloride and Rituximab (BR) Compared With Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in the First-Line Treatment of Patients With Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL)
Study Start Date :
Apr 30, 2009
Actual Primary Completion Date :
Mar 31, 2012
Actual Study Completion Date :
Mar 31, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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

Drug: bendamustine
Other Names:
  • Treakisym
  • Ribomustin
  • Levact
  • Treanda
  • SDX-105
  • Drug: rituximab
    Other Names:
  • Rituxan
  • MabThera
  • Zytux
  • Active Comparator: 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

    Drug: rituximab
    Other Names:
  • Rituxan
  • MabThera
  • Zytux
  • Drug: vincristine
    Other Names:
  • Oncovin
  • Drug: prednisone

    Drug: cyclophosphamide
    Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • Drug: doxorubicin
    Other Names:
  • Adriamycin
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Complete Response (CR) at End of Treatment Period [6 to 8 21 or 28-day cycles (18-32 weeks)]

      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.

    Secondary Outcome Measures

    1. Percentage of Participants With Overall Response at End of Treatment Period [6 to 8 21 or 28-day cycles (18-32 weeks)]

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

    2. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period [32 weeks]

      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.

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

      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).

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

      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).

    5. Clinically Significant Abnormal Vital Signs [32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)]

    6. Potentially Clinically Significant Abnormal Weight [Baseline, Week 32]

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

    7. Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period [Week 32]

      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).

    8. Therapeutic Classification of Prior Medications [prior to start of treatment]

    9. Therapeutic Classification of Concomitant Medications [32 weeks]

    10. 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) [Day 1 (prior to treatment), 32 weeks]

      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.

    11. Participants With Disease Progression, Relapse or Death At the End of the Treatment Period or the Long-Term Follow-up Period [Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment 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

    12. Kaplan-Meier Estimate for Progression-free Survival (PFS) [Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)]

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

    13. Kaplan-Meier Estimate for Event-free Survival (EFS) [Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)]

      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.

    14. Kaplan-Meier Estimate for Duration of Response (DOR) [Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)]

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

    15. Overall Survival (OS) [Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)]

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

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Teva Investigational Site 165 Tucson Arizona United States
    2 Teva Investigational Site 167 Little Rock Arkansas United States
    3 Teva Investigational Site 11 Corona California United States
    4 Teva Investigational Site 21 Fountain Valley California United States
    5 Teva Investigational Site 52 Fountain Valley California United States
    6 Teva Investigational Site 64 Fullerton California United States
    7 Teva Investigational Site 40 Los Angeles California United States
    8 Teva Investigational Site 53 Los Angeles California United States
    9 Teva Investigational Site 57 San Diego California United States
    10 Teva Investigational Site 15 Aurora Colorado United States
    11 Teva Investigational Site 155 Denver Colorado United States
    12 Teva Investigational Site 5 Fort Collins Colorado United States
    13 Teva Investigational Site 70 New Britain Connecticut United States
    14 Teva Investigational Site 37 Norwalk Connecticut United States
    15 Teva Investigational Site 67 Southington Connecticut United States
    16 Teva Investigational Site 58 Fort Myers Florida United States
    17 Teva Investigational Site 38 Hollywood Florida United States
    18 Teva Investigational Site 23 Jacksonville Florida United States
    19 Teva Investigational Site 65 Lake Worth Florida United States
    20 Teva Investigational Site 156 Miami Florida United States
    21 Teva Investigational Site 160 Orlando Florida United States
    22 Teva Investigational Site 68 Orlando Florida United States
    23 Teva Investigational Site 72 Augusta Georgia United States
    24 Teva Investigational Site 50 Columbus Georgia United States
    25 Teva Investigational Site 73 Macon Georgia United States
    26 Teva Investigational Site 49 Centralia Illinois United States
    27 Teva Investigational Site 48 Chicago Illinois United States
    28 Teva Investigational Site 9 Chicago Illinois United States
    29 Teva Investigational Site 14 Normal Illinois United States
    30 Teva Investigational Site 24 Beech Grove Indiana United States
    31 Teva Investigational Site 152 Indianapolis Indiana United States
    32 Teva Investigational Site 31 Iowa City Iowa United States
    33 Teva Investigational Site 63 Waterloo Iowa United States
    34 Teva Investigational Site 47 Wichita Kansas United States
    35 Teva Investigational Site 33 Lexington Kentucky United States
    36 Teva Investigational Site 19 Shreveport Louisiana United States
    37 Teva Investigational Site 43 Augusta Maine United States
    38 Teva Investigational Site 74 Lowell Massachusetts United States
    39 Teva Investigational Site 22 Duluth Minnesota United States
    40 Teva Investigational Site 4 Saint Louis Park Minnesota United States
    41 Teva Investigational Site 162 Columbia Missouri United States
    42 Teva Investigational Site 157 Kansas City Missouri United States
    43 Teva Investigational Site 29 Morristown New Jersey United States
    44 Teva Investigational Site 46 Albuquerque New Mexico United States
    45 Teva Investigational Site 8 Rochester New York United States
    46 Teva Investigational Site 10 Syracuse New York United States
    47 Teva Investigational Site 17 Charlotte North Carolina United States
    48 Teva Investigational Site 151 Durham North Carolina United States
    49 Teva Investigational Site 39 Fargo North Dakota United States
    50 Teva Investigational Site 34 Cincinnati Ohio United States
    51 Teva Investigational Site 60 Cincinnati Ohio United States
    52 Teva Investigational Site 28 Cleveland Ohio United States
    53 Teva Investigational Site 153 Springfield Oregon United States
    54 Teva Investigational Site 59 Bethlehem Pennsylvania United States
    55 Teva Investigational Site 44 Danville Pennsylvania United States
    56 Teva Investigational Site 3 Philadelphia Pennsylvania United States
    57 Teva Investigational Site 13 Pittsburgh Pennsylvania United States
    58 Teva Investigational Site 7 Pottstown Pennsylvania United States
    59 Teva Investigational Site 25 Charleston South Carolina United States
    60 Teva Investigational Site 71 Columbia South Carolina United States
    61 Teva Investigational Site 56 Chattanooga Tennessee United States
    62 Teva Investigational Site 30 Nashville Tennessee United States
    63 Teva Investigational Site 154 Arlington Texas United States
    64 Teva Investigational Site 158 Arlington Texas United States
    65 Teva Investigational Site 6 El Paso Texas United States
    66 Teva Investigational Site 161 Fort Worth Texas United States
    67 Teva Investigational Site 159 San Antonio Texas United States
    68 Teva Investigational Site 166 Sugar Land Texas United States
    69 Teva Investigational Site 2 Salt Lake City Utah United States
    70 Teva Investigational Site 18 Abingdon Virginia United States
    71 Teva Investigational Site 35 Charlottesville Virginia United States
    72 Teva Investigational Site 164 Norfolk Virginia United States
    73 Teva Investigational Site 54 Richmond Virginia United States
    74 Teva Investigational Site 42 Seattle Washington United States
    75 Teva Investigational Site 150 Spokane Washington United States
    76 Teva Investigational Site 163 Vancouver Washington United States
    77 Teva Investigational Site 66 Morgantown West Virginia United States
    78 Teva Investigational Site 41 Madison Wisconsin United States
    79 Teva Investigational Site 62 Wausau Wisconsin United States
    80 Teva Investigational Site 315 Perth Western Australia Australia
    81 Teva Investigational Site 305 Concord Australia
    82 Teva Investigational Site 317 Douglas Australia
    83 Teva Investigational Site 308 East Melbourne Australia
    84 Teva Investigational Site 310 Fitzroy Australia
    85 Teva Investigational Site 311 Fitzroy Australia
    86 Teva Investigational Site 301 Garran Australia
    87 Teva Investigational Site 316 Geelong Australia
    88 Teva Investigational Site 304 Hobart Australia
    89 Teva Investigational Site 312 Kurralta Park Australia
    90 Teva Investigational Site 307 Melbourne Australia
    91 Teva Investigational Site 318 Parkville Australia
    92 Teva Investigational Site 300 South Brisbane Australia
    93 Teva Investigational Site 303 Westmead Australia
    94 Teva Investigational Site 314 Wodonga Australia
    95 Teva Investigational Site 313 Woodville Australia
    96 Teva Investigational Site 309 Woolloongabba Australia
    97 Teva Investigational Site 503 Barretos Brazil
    98 Teva Investigational Site 504 Brasilia Brazil
    99 Teva Investigational Site 506 Curitiba Brazil
    100 Teva Investigational Site 505 Goiânia Brazil
    101 Teva Investigational Site 502 Jau Brazil
    102 Teva Investigational Site 509 Lajeado Brazil
    103 Teva Investigational Site 507 Porto Alegre Brazil
    104 Teva Investigational Site 508 Porto Alegre Brazil
    105 Teva Investigational Site 511 Rio De Janeiro Brazil
    106 Teva Investigational Site 500 Santo Andre Brazil
    107 Teva Investigational Site 501 Sao Paulo Brazil
    108 Teva Investigational Site 202 Barrie Canada
    109 Teva Investigational Site 206 Calgary Canada
    110 Teva Investigational Site 200 Halifax Canada
    111 Teva Investigational Site 201 Ottawa Canada
    112 Teva Investigational Site 203 Vancouver Canada
    113 Teva Investigational Site 204 Winnipeg Canada
    114 Teva Investigational Site 602 Aguascalientes Mexico
    115 Teva Investigational Site 603 Hermosillo Mexico
    116 Teva Investigational Site 600 Monterrey Mexico
    117 Teva Investigational Site 601 Monterrey Mexico
    118 Teva Investigational Site 401 Auckland New Zealand
    119 Teva Investigational Site 405 Auckland New Zealand
    120 Teva Investigational Site 400 Christchurch New Zealand
    121 Teva Investigational Site 402 Newtown New Zealand
    122 Teva Investigational Site 404 Palmerston North New Zealand
    123 Teva Investigational Site 403 Takapuna New Zealand
    124 Teva Investigational Site 700 Lima Peru
    125 Teva Investigational Site 701 Lima Peru
    126 Teva Investigational Site 704 Lima Peru
    127 Teva Investigational Site 702 Miraflores Peru
    128 Teva Investigational Site 703 Miraflores Peru

    Sponsors and Collaborators

    • Teva Branded Pharmaceutical Products R&D, Inc.

    Investigators

    • Study Director: Sponsor's Medical Expert, Cephalon

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Teva Branded Pharmaceutical Products R&D, Inc.
    ClinicalTrials.gov Identifier:
    NCT00877006
    Other Study ID Numbers:
    • C18083/3064/NL/MN
    First Posted:
    Apr 7, 2009
    Last Update Posted:
    Feb 5, 2018
    Last Verified:
    Jan 1, 2018

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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
    Period Title: Treatment Period
    STARTED 210 209
    COMPLETED 157 154
    NOT COMPLETED 53 55

    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 Participants 224 223 447
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    60.0
    (11.37)
    58.2
    (12.11)
    59.1
    (11.77)
    Sex: Female, Male (Count of Participants)
    Female
    88
    39.3%
    91
    40.8%
    179
    40%
    Male
    136
    60.7%
    132
    59.2%
    268
    60%
    European Cooperative Oncology Group Performance Status (participants) [Number]
    0
    144
    64.3%
    143
    64.1%
    287
    64.2%
    1
    70
    31.3%
    69
    30.9%
    139
    31.1%
    2
    9
    4%
    10
    4.5%
    19
    4.3%
    3
    1
    0.4%
    0
    0%
    1
    0.2%
    4
    0
    0%
    0
    0%
    0
    0%
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    81.9
    (18.48)
    82.4
    (17.93)
    82.1
    (18.19)

    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
    Measure Participants 213 206
    Number (95% Confidence Interval) [percentage of participants]
    31
    13.8%
    25
    11.2%
    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
    Measure Participants 213 206
    Number (95% Confidence Interval) [percentage of participants]
    97
    43.3%
    91
    40.8%
    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
    Measure Participants 221 215
    Any AE
    221
    98.7%
    213
    95.5%
    Severe AEs (grades 3, 4, 5)
    130
    58%
    127
    57%
    Treatment-related AEs
    209
    93.3%
    NA
    NaN
    Deaths
    12
    5.4%
    9
    4%
    SAEs
    60
    26.8%
    49
    22%
    Withdrawn due to AEs
    10
    4.5%
    3
    1.3%
    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
    Measure Participants 221 215
    Albumin: Grade 1
    33
    14.7%
    44
    19.7%
    Albumin: Grade 2
    14
    6.3%
    13
    5.8%
    Albumin: Grade 3
    3
    1.3%
    0
    0%
    Albumin: Grade 4
    0
    0%
    0
    0%
    Albumin: Grades 1-4
    50
    22.3%
    57
    25.6%
    Alkaline Phosphatase: Grade 1
    41
    18.3%
    25
    11.2%
    Alkaline Phosphatase: Grade 2
    1
    0.4%
    3
    1.3%
    Alkaline Phosphatase: Grade 3
    0
    0%
    0
    0%
    Alkaline Phosphatase: Grade 4
    0
    0%
    0
    0%
    Alkaline Phosphatase: Grades 1-4
    42
    18.8%
    28
    12.6%
    Creatinine: Grade 1
    19
    8.5%
    25
    11.2%
    Creatinine: Grade 2
    3
    1.3%
    1
    0.4%
    Creatinine: Grade 3
    1
    0.4%
    0
    0%
    Creatinine: Grade 4
    0
    0%
    0
    0%
    Creatinine: Grades 1-4
    23
    10.3%
    26
    11.7%
    Gamma-glutamyl transferase: Grade 1
    31
    13.8%
    37
    16.6%
    Gamma-glutamyl transferase: Grade 2
    18
    8%
    10
    4.5%
    Gamma-glutamyl transferase: Grade 3
    3
    1.3%
    6
    2.7%
    Gamma-glutamyl transferase: Grade 4
    0
    0%
    0
    0%
    Gamma-glutamyl transferase: Grades 1-4
    52
    23.2%
    53
    23.8%
    Hypercalcemia: Grade 1
    6
    2.7%
    6
    2.7%
    Hypercalcemia: Grade 2
    0
    0%
    0
    0%
    Hypercalcemia: Grade 3
    1
    0.4%
    0
    0%
    Hypercalcemia: Grade 4
    0
    0%
    0
    0%
    Hypercalcemia: Grades 1-4
    7
    3.1%
    6
    2.7%
    Hyperglycemia: Grade 1
    94
    42%
    74
    33.2%
    Hyperglycemia: Grade 2
    20
    8.9%
    34
    15.2%
    Hyperglycemia: Grade 3
    15
    6.7%
    15
    6.7%
    Hyperglycemia: Grade 4
    0
    0%
    1
    0.4%
    Hyperglycemia: Grades 1-4
    129
    57.6%
    124
    55.6%
    Hyperkalemia: Grade 1
    7
    3.1%
    8
    3.6%
    Hyperkalemia: Grade 2
    3
    1.3%
    1
    0.4%
    Hyperkalemia: Grade 3
    1
    0.4%
    0
    0%
    Hyperkalemia: Grade 4
    0
    0%
    0
    0%
    Hyperkalemia: Grades 1-4
    11
    4.9%
    9
    4%
    Hypernatremia: Grade 1
    8
    3.6%
    10
    4.5%
    Hypernatremia: Grade 2
    0
    0%
    0
    0%
    Hypernatremia: Grade 3
    0
    0%
    0
    0%
    Hypernatremia: Grade 4
    0
    0%
    0
    0%
    Hypernatremia: Grades 1-4
    8
    3.6%
    10
    4.5%
    Hypocalcemia: Grade 1
    36
    16.1%
    28
    12.6%
    Hypocalcemia: Grade 2
    8
    3.6%
    6
    2.7%
    Hypocalcemia: Grade 3
    1
    0.4%
    0
    0%
    Hypocalcemia: Grade 4
    3
    1.3%
    0
    0%
    Hypocalcemia: Grades 1-4
    48
    21.4%
    34
    15.2%
    Hypoglycemia: Grade 1
    15
    6.7%
    10
    4.5%
    Hypoglycemia: Grade 2
    1
    0.4%
    0
    0%
    Hypoglycemia: Grade 3
    0
    0%
    0
    0%
    Hypoglycemia: Grade 4
    0
    0%
    0
    0%
    Hypoglycemia: Grades 1-4
    16
    7.1%
    10
    4.5%
    Hypokalemia: Grade 1
    18
    8%
    16
    7.2%
    Hypokalemia: Grade 2
    0
    0%
    0
    0%
    Hypokalemia: Grade 3
    0
    0%
    1
    0.4%
    Hypokalemia: Grade 4
    0
    0%
    0
    0%
    Hypokalemia: Grades 1-4
    18
    8%
    17
    7.6%
    Hyponatremia: Grade 1
    40
    17.9%
    28
    12.6%
    Hyponatremia: Grade 2
    0
    0%
    0
    0%
    Hyponatremia: Grade 3
    0
    0%
    5
    2.2%
    Hyponatremia: Grade 4
    0
    0%
    0
    0%
    Hyponatremia: Grades 1-4
    40
    17.9%
    33
    14.8%
    Magnesium: Grade 1
    46
    20.5%
    44
    19.7%
    Magnesium: Grade 2
    0
    0%
    1
    0.4%
    Magnesium: Grade 3
    0
    0%
    1
    0.4%
    Magnesium: Grade 4
    0
    0%
    0
    0%
    Magnesium: Grades 1-4
    46
    20.5%
    46
    20.6%
    Phosphorus: Grade 1
    7
    3.1%
    5
    2.2%
    Phosphorus: Grade 2
    25
    11.2%
    22
    9.9%
    Phosphorus: Grade 3
    3
    1.3%
    3
    1.3%
    Phosphorus: Grade 4
    0
    0%
    1
    0.4%
    Phosphorus: Grades 1-4
    35
    15.6%
    31
    13.9%
    Aspartate Aminotransferase: Grade 1
    42
    18.8%
    32
    14.3%
    Aspartate Aminotransferase: Grade 2
    2
    0.9%
    2
    0.9%
    Aspartate Aminotransferase: Grade 3
    1
    0.4%
    1
    0.4%
    Aspartate Aminotransferase: Grade 4
    0
    0%
    0
    0%
    Aspartate Aminotransferase: Grades 1-4
    45
    20.1%
    35
    15.7%
    Alanine Aminotransferase: Grade 1
    46
    20.5%
    38
    17%
    Alanine Aminotransferase: Grade 2
    6
    2.7%
    3
    1.3%
    Alanine Aminotransferase: Grade 3
    2
    0.9%
    1
    0.4%
    Alanine Aminotransferase: Grade 4
    0
    0%
    0
    0%
    Alanine Aminotransferase: Grades 1-4
    54
    24.1%
    42
    18.8%
    Total Bilirubin: Grade 1
    14
    6.3%
    7
    3.1%
    Total Bilirubin: Grade 2
    1
    0.4%
    0
    0%
    Total Bilirubin: Grade 3
    0
    0%
    0
    0%
    Total Bilirubin: Grade 4
    0
    0%
    0
    0%
    Total Bilirubin: Grades 1-4
    15
    6.7%
    7
    3.1%
    Uric Acid: Grade 1
    41
    18.3%
    42
    18.8%
    Uric Acid: Grade 2
    0
    0%
    0
    0%
    Uric Acid: Grade 3
    0
    0%
    0
    0%
    Uric Acid: Grade 4
    1
    0.4%
    0
    0%
    Uric Acid: Grades 1-4
    42
    18.8%
    42
    18.8%
    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
    Measure Participants 221 215
    Absolute Neutrophil Count: Grade 1
    22
    9.8%
    14
    6.3%
    Absolute Neutrophil Count: Grade 2
    51
    22.8%
    20
    9%
    Absolute Neutrophil Count: Grade 3
    48
    21.4%
    47
    21.1%
    Absolute Neutrophil Count: Grade 4
    50
    22.3%
    104
    46.6%
    Absolute Neutrophil Count: Grades 1-4
    171
    76.3%
    185
    83%
    Hemoglobin: Grade 1
    129
    57.6%
    129
    57.8%
    Hemoglobin: Grade 2
    42
    18.8%
    51
    22.9%
    Hemoglobin: Grade 3
    5
    2.2%
    7
    3.1%
    Hemoglobin: Grade 4
    1
    0.4%
    2
    0.9%
    Hemoglobin: Grades 1-4
    177
    79%
    189
    84.8%
    Lymphocytes Absolute: Grade 1
    1
    0.4%
    6
    2.7%
    Lymphocytes Absolute: Grade 2
    5
    2.2%
    55
    24.7%
    Lymphocytes Absolute: Grade 3
    54
    24.1%
    55
    24.7%
    Lymphocytes Absolute: Grade 4
    83
    37.1%
    9
    4%
    Lymphocytes Absolute: Grades 1-4
    143
    63.8%
    125
    56.1%
    Platelets: Grade 1
    106
    47.3%
    72
    32.3%
    Platelets: Grade 2
    14
    6.3%
    14
    6.3%
    Platelets: Grade 3
    9
    4%
    7
    3.1%
    Platelets: Grade 4
    7
    3.1%
    8
    3.6%
    Platelets: Grades 1-4
    136
    60.7%
    101
    45.3%
    White Blood Cells: Grade 1
    41
    18.3%
    22
    9.9%
    White Blood Cells: Grade 2
    79
    35.3%
    49
    22%
    White Blood Cells: Grade 3
    65
    29%
    89
    39.9%
    White Blood Cells: Grade 4
    19
    8.5%
    27
    12.1%
    White Blood Cells: Grades 1-4
    204
    91.1%
    187
    83.9%
    6. Secondary Outcome
    Title Clinically Significant Abnormal Vital Signs
    Description
    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
    Measure Participants 220 212
    Heart Rate >=120 and ↑ >=15 bpm
    0
    0%
    1
    0.4%
    Heart Rate <=50 and ↓ >=15 bpm
    2
    0.9%
    2
    0.9%
    Systolic Blood Pressure(BP) >=180 and ↑ >=20 mm Hg
    2
    0.9%
    2
    0.9%
    Systolic BP <=90 and ↓ >=20 mm Hg
    6
    2.7%
    2
    0.9%
    Diastolic BP >=105 and ↑ from Baseline >=15 mm Hg
    1
    0.4%
    2
    0.9%
    Diastolic BP <=50 and ↓ from Baseline >=15 mm Hg
    2
    0.9%
    2
    0.9%
    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
    Measure Participants 220 212
    Increase >=10%
    8
    3.6%
    5
    2.2%
    Decrease >=10%
    18
    8%
    8
    3.6%
    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.
    Measure Participants 219 211
    Improved
    32
    14.3%
    28
    12.6%
    Stayed the Same
    153
    68.3%
    141
    63.2%
    Worsened
    34
    15.2%
    42
    18.8%
    9. Secondary Outcome
    Title Therapeutic Classification of Prior Medications
    Description
    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
    Measure Participants 224 223
    Psycholeptics
    57
    25.4%
    59
    26.5%
    Sex Hormones and Modulators of the Genital System
    11
    4.9%
    12
    5.4%
    Stomatological Preparations
    0
    0%
    0
    0%
    Throat Preparations
    0
    0%
    0
    0%
    Thyroid Therapy
    16
    7.1%
    17
    7.6%
    Topical Products for Join and Muscular Pain
    1
    0.4%
    0
    0%
    Unspecified Herbal
    10
    4.5%
    10
    4.5%
    Urologicals
    20
    8.9%
    11
    4.9%
    Vaccines
    2
    0.9%
    7
    3.1%
    Vasoprotectives
    0
    0%
    0
    0%
    Vitamins
    70
    31.3%
    61
    27.4%
    10. Secondary Outcome
    Title Therapeutic Classification of Concomitant Medications
    Description
    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
    Measure Participants 221 215
    Psycholeptics
    69
    30.8%
    74
    33.2%
    Sex Hormones and Modulators of the Genital System
    6
    2.7%
    4
    1.8%
    Stomatological Preparations
    23
    10.3%
    29
    13%
    Throat Preparations
    3
    1.3%
    2
    0.9%
    Thyroid Therapy
    3
    1.3%
    1
    0.4%
    Topical Preparations for Join and Muscular Pain
    1
    0.4%
    2
    0.9%
    Unspecified Herbal
    3
    1.3%
    5
    2.2%
    Urologicals
    5
    2.2%
    4
    1.8%
    Vaccines
    11
    4.9%
    11
    4.9%
    Vasoprotectives
    1
    0.4%
    8
    3.6%
    Vitamins
    16
    7.1%
    21
    9.4%
    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
    Measure Participants 211 207
    Mean (Standard Deviation) [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
    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
    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
    Measure Participants 224 223
    Count of Participants [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
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9677
    Comments
    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
    Parameter Dispersion Type:
    Value:
    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
    Measure Participants 224 223
    Median (95% Confidence Interval) [months]
    31.8
    33.4
    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
    Measure Participants 224 223
    Median (95% Confidence Interval) [months]
    31.8
    32.6
    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
    Measure Participants 210 187
    Median (95% Confidence Interval) [months]
    26.5
    32.1
    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
    Measure Participants 224 223
    Median (95% Confidence Interval) [months]
    65.0
    64.1
    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
    Measure Participants 224 223
    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%
    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 (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Bendamustine and Rituximab (BR) R-CHOP/CVP
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 60/221 (27.1%) 49/215 (22.8%)
    Blood and lymphatic system disorders
    Aplasia pure red cell 1/221 (0.5%) 1 0/215 (0%) 0
    Febrile neutropenia 7/221 (3.2%) 8 9/215 (4.2%) 10
    Lymphadenopathy 0/221 (0%) 0 1/215 (0.5%) 1
    Neutropenia 4/221 (1.8%) 6 5/215 (2.3%) 6
    Splenomegaly 1/221 (0.5%) 1 0/215 (0%) 0
    Cardiac disorders
    Atrial fibrillation 0/221 (0%) 0 1/215 (0.5%) 1
    Atrioventricular block first degree 1/221 (0.5%) 1 0/215 (0%) 0
    Bundle branch block left 0/221 (0%) 0 1/215 (0.5%) 1
    Cardiac arrest 1/221 (0.5%) 1 1/215 (0.5%) 1
    Cardiac failure congestive 0/221 (0%) 0 1/215 (0.5%) 1
    Left ventricular dysfunction 1/221 (0.5%) 1 1/215 (0.5%) 2
    Myocardial infarction 0/221 (0%) 0 1/215 (0.5%) 1
    Pericardial effusion 1/221 (0.5%) 1 0/215 (0%) 0
    Supraventricular tachycardia 0/221 (0%) 0 1/215 (0.5%) 1
    Eye disorders
    Vitreous floaters 1/221 (0.5%) 1 0/215 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 2/221 (0.9%) 3 1/215 (0.5%) 1
    Ascites 1/221 (0.5%) 1 0/215 (0%) 0
    Constipation 1/221 (0.5%) 1 0/215 (0%) 0
    Diarrhoea 1/221 (0.5%) 1 0/215 (0%) 0
    Diverticular perforation 0/221 (0%) 0 1/215 (0.5%) 1
    Gastrooesophageal reflux disease 1/221 (0.5%) 1 0/215 (0%) 0
    Ileus 1/221 (0.5%) 1 0/215 (0%) 0
    Nausea 3/221 (1.4%) 3 0/215 (0%) 0
    Rectal haemorrhage 1/221 (0.5%) 1 0/215 (0%) 0
    Small intestinal obstruction 1/221 (0.5%) 1 1/215 (0.5%) 1
    Vomiting 3/221 (1.4%) 3 0/215 (0%) 0
    General disorders
    Chills 1/221 (0.5%) 2 0/215 (0%) 0
    Non-cardiac chest pain 0/221 (0%) 0 3/215 (1.4%) 3
    Pyrexia 5/221 (2.3%) 6 4/215 (1.9%) 5
    Hepatobiliary disorders
    Cholelithiasis 1/221 (0.5%) 1 0/215 (0%) 0
    Portal vein thrombosis 1/221 (0.5%) 1 0/215 (0%) 0
    Immune system disorders
    Anaphylactic shock 1/221 (0.5%) 1 0/215 (0%) 0
    Drug hypersensitivity 4/221 (1.8%) 4 0/215 (0%) 0
    Infections and infestations
    Abscess limb 0/221 (0%) 0 1/215 (0.5%) 1
    Anal infection 0/221 (0%) 0 1/215 (0.5%) 1
    Bacteraemia 1/221 (0.5%) 1 0/215 (0%) 0
    Clostridium difficile colitis 1/221 (0.5%) 1 0/215 (0%) 0
    Diverticulitis 2/221 (0.9%) 3 1/215 (0.5%) 1
    Gastroenteritis 1/221 (0.5%) 1 0/215 (0%) 0
    Gastrointestinal infection 1/221 (0.5%) 1 0/215 (0%) 0
    Infection 1/221 (0.5%) 1 0/215 (0%) 0
    Infective exacerbation of chronic obstructive airways disease 1/221 (0.5%) 1 0/215 (0%) 0
    Lower respiratory tract infection 0/221 (0%) 0 1/215 (0.5%) 1
    Pharyngitis 0/221 (0%) 0 1/215 (0.5%) 1
    Pneumocystis jiroveci infection 1/221 (0.5%) 1 0/215 (0%) 0
    Pneumocystis jiroveci pneumonia 1/221 (0.5%) 1 1/215 (0.5%) 1
    Pneumonia 7/221 (3.2%) 7 1/215 (0.5%) 1
    Postoperative wound infection 0/221 (0%) 0 1/215 (0.5%) 1
    Septic shock 1/221 (0.5%) 1 1/215 (0.5%) 2
    Tooth abscess 1/221 (0.5%) 1 0/215 (0%) 0
    Tooth infection 0/221 (0%) 0 1/215 (0.5%) 1
    Tracheobronchitis 1/221 (0.5%) 1 0/215 (0%) 0
    Upper respiratory tract infection 1/221 (0.5%) 1 0/215 (0%) 0
    Urinary tract infection 1/221 (0.5%) 1 0/215 (0%) 0
    Viral infection 2/221 (0.9%) 2 0/215 (0%) 0
    Injury, poisoning and procedural complications
    Ankle fracture 0/221 (0%) 0 1/215 (0.5%) 1
    Cervical vertebral fracture 0/221 (0%) 0 1/215 (0.5%) 1
    Clavicle fracture 0/221 (0%) 0 1/215 (0.5%) 1
    Fall 0/221 (0%) 0 1/215 (0.5%) 1
    Infusion related reaction 8/221 (3.6%) 11 4/215 (1.9%) 4
    Procedural complication 0/221 (0%) 0 1/215 (0.5%) 1
    Rib fracture 1/221 (0.5%) 1 1/215 (0.5%) 1
    Spinal compression fracture 0/221 (0%) 0 1/215 (0.5%) 1
    Toxicity to various agents 1/221 (0.5%) 1 0/215 (0%) 0
    Investigations
    Electrocardiogram QT prolonged 0/221 (0%) 0 1/215 (0.5%) 1
    Metabolism and nutrition disorders
    Dehydration 0/221 (0%) 0 1/215 (0.5%) 1
    Hyperglycaemia 0/221 (0%) 0 1/215 (0.5%) 1
    Tumour lysis syndrome 1/221 (0.5%) 1 0/215 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 0/221 (0%) 0 2/215 (0.9%) 3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung neoplasm malignant 1/221 (0.5%) 2 0/215 (0%) 0
    Renal cell carcinoma 0/221 (0%) 0 1/215 (0.5%) 1
    Sarcoma 1/221 (0.5%) 1 0/215 (0%) 0
    Nervous system disorders
    Dystonia 0/221 (0%) 0 1/215 (0.5%) 1
    Headache 1/221 (0.5%) 1 0/215 (0%) 0
    Intracranial aneurysm 0/221 (0%) 0 1/215 (0.5%) 1
    Neuropathy peripheral 1/221 (0.5%) 1 0/215 (0%) 0
    Syncope 1/221 (0.5%) 1 1/215 (0.5%) 1
    Psychiatric disorders
    Confusional state 1/221 (0.5%) 1 0/215 (0%) 0
    Depression 0/221 (0%) 0 1/215 (0.5%) 1
    Renal and urinary disorders
    Haematuria 1/221 (0.5%) 1 0/215 (0%) 0
    Renal failure acute 1/221 (0.5%) 1 0/215 (0%) 0
    Renal tubular necrosis 1/221 (0.5%) 1 0/215 (0%) 0
    Urinary retention 1/221 (0.5%) 1 0/215 (0%) 0
    Reproductive system and breast disorders
    Prostatitis 1/221 (0.5%) 1 0/215 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/221 (0.5%) 1 0/215 (0%) 0
    Chronic obstructive pulmonary disease 2/221 (0.9%) 3 0/215 (0%) 0
    Dyspnoea 0/221 (0%) 0 1/215 (0.5%) 1
    Hypoxia 1/221 (0.5%) 1 1/215 (0.5%) 1
    Interstitial lung disease 1/221 (0.5%) 1 0/215 (0%) 0
    Pleural effusion 1/221 (0.5%) 1 0/215 (0%) 0
    Pulmonary embolism 1/221 (0.5%) 1 1/215 (0.5%) 1
    Respiratory failure 2/221 (0.9%) 2 0/215 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash 1/221 (0.5%) 1 0/215 (0%) 0
    Rash maculo-papular 0/221 (0%) 0 1/215 (0.5%) 1
    Vascular disorders
    Hypertension 0/221 (0%) 0 1/215 (0.5%) 1
    Hypotension 1/221 (0.5%) 1 0/215 (0%) 0
    Other (Not Including Serious) Adverse Events
    Bendamustine and Rituximab (BR) R-CHOP/CVP
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 216/221 (97.7%) 211/215 (98.1%)
    Blood and lymphatic system disorders
    Anaemia 31/221 (14%) 63 29/215 (13.5%) 69
    Febrile neutropenia 7/221 (3.2%) 9 11/215 (5.1%) 12
    Leukopenia 21/221 (9.5%) 79 22/215 (10.2%) 88
    Lymphopenia 14/221 (6.3%) 104 12/215 (5.6%) 44
    Neutropenia 76/221 (34.4%) 251 85/215 (39.5%) 255
    Thrombocytopenia 29/221 (13.1%) 67 13/215 (6%) 54
    Gastrointestinal disorders
    Abdominal pain 25/221 (11.3%) 33 27/215 (12.6%) 31
    Abdominal pain upper 11/221 (5%) 11 14/215 (6.5%) 16
    Constipation 65/221 (29.4%) 85 90/215 (41.9%) 121
    Diarrhoea 46/221 (20.8%) 65 50/215 (23.3%) 72
    Dyspepsia 23/221 (10.4%) 23 26/215 (12.1%) 29
    Gastrooesophageal reflux disease 16/221 (7.2%) 16 17/215 (7.9%) 18
    Nausea 139/221 (62.9%) 255 102/215 (47.4%) 139
    Stomatitis 15/221 (6.8%) 20 14/215 (6.5%) 17
    Vomiting 60/221 (27.1%) 86 28/215 (13%) 35
    General disorders
    Asthenia 14/221 (6.3%) 16 17/215 (7.9%) 24
    Chest discomfort 8/221 (3.6%) 10 13/215 (6%) 14
    Chills 25/221 (11.3%) 34 11/215 (5.1%) 14
    Fatigue 113/221 (51.1%) 179 107/215 (49.8%) 147
    Mucosal inflammation 12/221 (5.4%) 15 26/215 (12.1%) 36
    Oedema peripheral 19/221 (8.6%) 23 23/215 (10.7%) 27
    Pain 14/221 (6.3%) 15 14/215 (6.5%) 17
    Pyrexia 37/221 (16.7%) 45 28/215 (13%) 31
    Immune system disorders
    Drug hypersensitivity 24/221 (10.9%) 32 8/215 (3.7%) 9
    Infections and infestations
    Nasopharyngitis 9/221 (4.1%) 9 11/215 (5.1%) 11
    Sinusitis 5/221 (2.3%) 7 12/215 (5.6%) 14
    Upper respiratory tract infection 22/221 (10%) 26 17/215 (7.9%) 20
    Injury, poisoning and procedural complications
    Infusion related reaction 52/221 (23.5%) 115 45/215 (20.9%) 64
    Investigations
    Neutrophil count decreased 9/221 (4.1%) 15 12/215 (5.6%) 18
    Weight decreased 14/221 (6.3%) 14 7/215 (3.3%) 8
    Metabolism and nutrition disorders
    Decreased appetite 42/221 (19%) 57 26/215 (12.1%) 26
    Hyperglycaemia 4/221 (1.8%) 9 11/215 (5.1%) 26
    Musculoskeletal and connective tissue disorders
    Arthralgia 28/221 (12.7%) 33 32/215 (14.9%) 46
    Back pain 23/221 (10.4%) 26 27/215 (12.6%) 39
    Bone pain 9/221 (4.1%) 10 18/215 (8.4%) 20
    Muscle spasms 6/221 (2.7%) 6 11/215 (5.1%) 14
    Musculoskeletal pain 12/221 (5.4%) 12 17/215 (7.9%) 18
    Myalgia 13/221 (5.9%) 15 18/215 (8.4%) 21
    Pain in extremity 17/221 (7.7%) 23 18/215 (8.4%) 20
    Nervous system disorders
    Dizziness 18/221 (8.1%) 31 21/215 (9.8%) 29
    Dysgeusia 28/221 (12.7%) 32 25/215 (11.6%) 25
    Headache 48/221 (21.7%) 60 45/215 (20.9%) 68
    Neuropathy peripheral 9/221 (4.1%) 13 51/215 (23.7%) 77
    Paraesthesia 7/221 (3.2%) 8 25/215 (11.6%) 29
    Peripheral sensory neuropathy 4/221 (1.8%) 4 20/215 (9.3%) 24
    Psychiatric disorders
    Anxiety 17/221 (7.7%) 18 18/215 (8.4%) 20
    Insomnia 37/221 (16.7%) 42 47/215 (21.9%) 53
    Respiratory, thoracic and mediastinal disorders
    Cough 34/221 (15.4%) 37 34/215 (15.8%) 36
    Dyspnoea 17/221 (7.7%) 23 26/215 (12.1%) 28
    Oropharyngeal pain 18/221 (8.1%) 20 16/215 (7.4%) 18
    Skin and subcutaneous tissue disorders
    Alopecia 8/221 (3.6%) 8 74/215 (34.4%) 83
    Dry skin 12/221 (5.4%) 13 7/215 (3.3%) 7
    Night sweats 7/221 (3.2%) 7 15/215 (7%) 15
    Pruritus 22/221 (10%) 26 10/215 (4.7%) 10
    Rash 33/221 (14.9%) 40 17/215 (7.9%) 20
    Vascular disorders
    Hypotension 12/221 (5.4%) 13 7/215 (3.3%) 8

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    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
    Responsible Party:
    Teva Branded Pharmaceutical Products R&D, Inc.
    ClinicalTrials.gov Identifier:
    NCT00877006
    Other Study ID Numbers:
    • C18083/3064/NL/MN
    First Posted:
    Apr 7, 2009
    Last Update Posted:
    Feb 5, 2018
    Last Verified:
    Jan 1, 2018