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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

Primary Purpose

Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
bendamustine
rituximab
vincristine
prednisone
cyclophosphamide
doxorubicin
Sponsored by
Teva Branded Pharmaceutical Products R&D, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Teva Investigational Site 165
  • Teva Investigational Site 167
  • Teva Investigational Site 11
  • Teva Investigational Site 21
  • Teva Investigational Site 52
  • Teva Investigational Site 64
  • Teva Investigational Site 40
  • Teva Investigational Site 53
  • Teva Investigational Site 57
  • Teva Investigational Site 15
  • Teva Investigational Site 155
  • Teva Investigational Site 5
  • Teva Investigational Site 70
  • Teva Investigational Site 37
  • Teva Investigational Site 67
  • Teva Investigational Site 58
  • Teva Investigational Site 38
  • Teva Investigational Site 23
  • Teva Investigational Site 65
  • Teva Investigational Site 156
  • Teva Investigational Site 160
  • Teva Investigational Site 68
  • Teva Investigational Site 72
  • Teva Investigational Site 50
  • Teva Investigational Site 73
  • Teva Investigational Site 49
  • Teva Investigational Site 48
  • Teva Investigational Site 9
  • Teva Investigational Site 14
  • Teva Investigational Site 24
  • Teva Investigational Site 152
  • Teva Investigational Site 31
  • Teva Investigational Site 63
  • Teva Investigational Site 47
  • Teva Investigational Site 33
  • Teva Investigational Site 19
  • Teva Investigational Site 43
  • Teva Investigational Site 74
  • Teva Investigational Site 22
  • Teva Investigational Site 4
  • Teva Investigational Site 162
  • Teva Investigational Site 157
  • Teva Investigational Site 29
  • Teva Investigational Site 46
  • Teva Investigational Site 8
  • Teva Investigational Site 10
  • Teva Investigational Site 17
  • Teva Investigational Site 151
  • Teva Investigational Site 39
  • Teva Investigational Site 34
  • Teva Investigational Site 60
  • Teva Investigational Site 28
  • Teva Investigational Site 153
  • Teva Investigational Site 59
  • Teva Investigational Site 44
  • Teva Investigational Site 3
  • Teva Investigational Site 13
  • Teva Investigational Site 7
  • Teva Investigational Site 25
  • Teva Investigational Site 71
  • Teva Investigational Site 56
  • Teva Investigational Site 30
  • Teva Investigational Site 154
  • Teva Investigational Site 158
  • Teva Investigational Site 6
  • Teva Investigational Site 161
  • Teva Investigational Site 159
  • Teva Investigational Site 166
  • Teva Investigational Site 2
  • Teva Investigational Site 18
  • Teva Investigational Site 35
  • Teva Investigational Site 164
  • Teva Investigational Site 54
  • Teva Investigational Site 42
  • Teva Investigational Site 150
  • Teva Investigational Site 163
  • Teva Investigational Site 66
  • Teva Investigational Site 41
  • Teva Investigational Site 62
  • Teva Investigational Site 315
  • Teva Investigational Site 305
  • Teva Investigational Site 317
  • Teva Investigational Site 308
  • Teva Investigational Site 310
  • Teva Investigational Site 311
  • Teva Investigational Site 301
  • Teva Investigational Site 316
  • Teva Investigational Site 304
  • Teva Investigational Site 312
  • Teva Investigational Site 307
  • Teva Investigational Site 318
  • Teva Investigational Site 300
  • Teva Investigational Site 303
  • Teva Investigational Site 314
  • Teva Investigational Site 313
  • Teva Investigational Site 309
  • Teva Investigational Site 503
  • Teva Investigational Site 504
  • Teva Investigational Site 506
  • Teva Investigational Site 505
  • Teva Investigational Site 502
  • Teva Investigational Site 509
  • Teva Investigational Site 507
  • Teva Investigational Site 508
  • Teva Investigational Site 511
  • Teva Investigational Site 500
  • Teva Investigational Site 501
  • Teva Investigational Site 202
  • Teva Investigational Site 206
  • Teva Investigational Site 200
  • Teva Investigational Site 201
  • Teva Investigational Site 203
  • Teva Investigational Site 204
  • Teva Investigational Site 602
  • Teva Investigational Site 603
  • Teva Investigational Site 600
  • Teva Investigational Site 601
  • Teva Investigational Site 401
  • Teva Investigational Site 405
  • Teva Investigational Site 400
  • Teva Investigational Site 402
  • Teva Investigational Site 404
  • Teva Investigational Site 403
  • Teva Investigational Site 700
  • Teva Investigational Site 701
  • Teva Investigational Site 704
  • Teva Investigational Site 702
  • Teva Investigational Site 703

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Bendamustine and Rituximab (BR)

R-CHOP/R-CVP

Arm 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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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).
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).
Clinically Significant Abnormal Vital Signs
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.
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).
Therapeutic Classification of Prior Medications
Therapeutic Classification of Concomitant Medications
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.
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
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.
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.
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.
Overall Survival (OS)
OS was defined as the time from randomization to death from any cause.
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.

Full Information

First Posted
April 3, 2009
Last Updated
January 8, 2018
Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00877006
Brief Title
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
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 Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
April 30, 2009 (undefined)
Primary Completion Date
March 31, 2012 (Actual)
Study Completion Date
March 31, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
447 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bendamustine and Rituximab (BR)
Arm Type
Experimental
Arm 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
Arm Title
R-CHOP/R-CVP
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
bendamustine
Other Intervention Name(s)
Treakisym, Ribomustin, Levact, Treanda, SDX-105
Intervention Type
Drug
Intervention Name(s)
rituximab
Other Intervention Name(s)
Rituxan, MabThera, Zytux
Intervention Type
Drug
Intervention Name(s)
vincristine
Other Intervention Name(s)
Oncovin
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
Endoxan, Cytoxan, Neosar, Procytox, Revimmune
Intervention Type
Drug
Intervention Name(s)
doxorubicin
Other Intervention Name(s)
Adriamycin
Primary Outcome Measure Information:
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)
Secondary Outcome Measure Information:
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)
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
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)
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)
Title
Clinically Significant Abnormal Vital Signs
Time Frame
32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)
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
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
Title
Therapeutic Classification of Prior Medications
Time Frame
prior to start of treatment
Title
Therapeutic Classification of Concomitant Medications
Time Frame
32 weeks
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
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
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)
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)
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)
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)
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: fever (>38ºC) of unclear etiology night sweats 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sponsor's Medical Expert
Organizational Affiliation
Cephalon
Official's Role
Study Director
Facility Information:
Facility Name
Teva Investigational Site 165
City
Tucson
State/Province
Arizona
Country
United States
Facility Name
Teva Investigational Site 167
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
Teva Investigational Site 11
City
Corona
State/Province
California
Country
United States
Facility Name
Teva Investigational Site 21
City
Fountain Valley
State/Province
California
Country
United States
Facility Name
Teva Investigational Site 52
City
Fountain Valley
State/Province
California
Country
United States
Facility Name
Teva Investigational Site 64
City
Fullerton
State/Province
California
Country
United States
Facility Name
Teva Investigational Site 40
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Teva Investigational Site 53
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Teva Investigational Site 57
City
San Diego
State/Province
California
Country
United States
Facility Name
Teva Investigational Site 15
City
Aurora
State/Province
Colorado
Country
United States
Facility Name
Teva Investigational Site 155
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Teva Investigational Site 5
City
Fort Collins
State/Province
Colorado
Country
United States
Facility Name
Teva Investigational Site 70
City
New Britain
State/Province
Connecticut
Country
United States
Facility Name
Teva Investigational Site 37
City
Norwalk
State/Province
Connecticut
Country
United States
Facility Name
Teva Investigational Site 67
City
Southington
State/Province
Connecticut
Country
United States
Facility Name
Teva Investigational Site 58
City
Fort Myers
State/Province
Florida
Country
United States
Facility Name
Teva Investigational Site 38
City
Hollywood
State/Province
Florida
Country
United States
Facility Name
Teva Investigational Site 23
City
Jacksonville
State/Province
Florida
Country
United States
Facility Name
Teva Investigational Site 65
City
Lake Worth
State/Province
Florida
Country
United States
Facility Name
Teva Investigational Site 156
City
Miami
State/Province
Florida
Country
United States
Facility Name
Teva Investigational Site 160
City
Orlando
State/Province
Florida
Country
United States
Facility Name
Teva Investigational Site 68
City
Orlando
State/Province
Florida
Country
United States
Facility Name
Teva Investigational Site 72
City
Augusta
State/Province
Georgia
Country
United States
Facility Name
Teva Investigational Site 50
City
Columbus
State/Province
Georgia
Country
United States
Facility Name
Teva Investigational Site 73
City
Macon
State/Province
Georgia
Country
United States
Facility Name
Teva Investigational Site 49
City
Centralia
State/Province
Illinois
Country
United States
Facility Name
Teva Investigational Site 48
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Teva Investigational Site 9
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Teva Investigational Site 14
City
Normal
State/Province
Illinois
Country
United States
Facility Name
Teva Investigational Site 24
City
Beech Grove
State/Province
Indiana
Country
United States
Facility Name
Teva Investigational Site 152
City
Indianapolis
State/Province
Indiana
Country
United States
Facility Name
Teva Investigational Site 31
City
Iowa City
State/Province
Iowa
Country
United States
Facility Name
Teva Investigational Site 63
City
Waterloo
State/Province
Iowa
Country
United States
Facility Name
Teva Investigational Site 47
City
Wichita
State/Province
Kansas
Country
United States
Facility Name
Teva Investigational Site 33
City
Lexington
State/Province
Kentucky
Country
United States
Facility Name
Teva Investigational Site 19
City
Shreveport
State/Province
Louisiana
Country
United States
Facility Name
Teva Investigational Site 43
City
Augusta
State/Province
Maine
Country
United States
Facility Name
Teva Investigational Site 74
City
Lowell
State/Province
Massachusetts
Country
United States
Facility Name
Teva Investigational Site 22
City
Duluth
State/Province
Minnesota
Country
United States
Facility Name
Teva Investigational Site 4
City
Saint Louis Park
State/Province
Minnesota
Country
United States
Facility Name
Teva Investigational Site 162
City
Columbia
State/Province
Missouri
Country
United States
Facility Name
Teva Investigational Site 157
City
Kansas City
State/Province
Missouri
Country
United States
Facility Name
Teva Investigational Site 29
City
Morristown
State/Province
New Jersey
Country
United States
Facility Name
Teva Investigational Site 46
City
Albuquerque
State/Province
New Mexico
Country
United States
Facility Name
Teva Investigational Site 8
City
Rochester
State/Province
New York
Country
United States
Facility Name
Teva Investigational Site 10
City
Syracuse
State/Province
New York
Country
United States
Facility Name
Teva Investigational Site 17
City
Charlotte
State/Province
North Carolina
Country
United States
Facility Name
Teva Investigational Site 151
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
Teva Investigational Site 39
City
Fargo
State/Province
North Dakota
Country
United States
Facility Name
Teva Investigational Site 34
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Teva Investigational Site 60
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Teva Investigational Site 28
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
Teva Investigational Site 153
City
Springfield
State/Province
Oregon
Country
United States
Facility Name
Teva Investigational Site 59
City
Bethlehem
State/Province
Pennsylvania
Country
United States
Facility Name
Teva Investigational Site 44
City
Danville
State/Province
Pennsylvania
Country
United States
Facility Name
Teva Investigational Site 3
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Teva Investigational Site 13
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
Teva Investigational Site 7
City
Pottstown
State/Province
Pennsylvania
Country
United States
Facility Name
Teva Investigational Site 25
City
Charleston
State/Province
South Carolina
Country
United States
Facility Name
Teva Investigational Site 71
City
Columbia
State/Province
South Carolina
Country
United States
Facility Name
Teva Investigational Site 56
City
Chattanooga
State/Province
Tennessee
Country
United States
Facility Name
Teva Investigational Site 30
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Teva Investigational Site 154
City
Arlington
State/Province
Texas
Country
United States
Facility Name
Teva Investigational Site 158
City
Arlington
State/Province
Texas
Country
United States
Facility Name
Teva Investigational Site 6
City
El Paso
State/Province
Texas
Country
United States
Facility Name
Teva Investigational Site 161
City
Fort Worth
State/Province
Texas
Country
United States
Facility Name
Teva Investigational Site 159
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
Teva Investigational Site 166
City
Sugar Land
State/Province
Texas
Country
United States
Facility Name
Teva Investigational Site 2
City
Salt Lake City
State/Province
Utah
Country
United States
Facility Name
Teva Investigational Site 18
City
Abingdon
State/Province
Virginia
Country
United States
Facility Name
Teva Investigational Site 35
City
Charlottesville
State/Province
Virginia
Country
United States
Facility Name
Teva Investigational Site 164
City
Norfolk
State/Province
Virginia
Country
United States
Facility Name
Teva Investigational Site 54
City
Richmond
State/Province
Virginia
Country
United States
Facility Name
Teva Investigational Site 42
City
Seattle
State/Province
Washington
Country
United States
Facility Name
Teva Investigational Site 150
City
Spokane
State/Province
Washington
Country
United States
Facility Name
Teva Investigational Site 163
City
Vancouver
State/Province
Washington
Country
United States
Facility Name
Teva Investigational Site 66
City
Morgantown
State/Province
West Virginia
Country
United States
Facility Name
Teva Investigational Site 41
City
Madison
State/Province
Wisconsin
Country
United States
Facility Name
Teva Investigational Site 62
City
Wausau
State/Province
Wisconsin
Country
United States
Facility Name
Teva Investigational Site 315
City
Perth
State/Province
Western Australia
Country
Australia
Facility Name
Teva Investigational Site 305
City
Concord
Country
Australia
Facility Name
Teva Investigational Site 317
City
Douglas
Country
Australia
Facility Name
Teva Investigational Site 308
City
East Melbourne
Country
Australia
Facility Name
Teva Investigational Site 310
City
Fitzroy
Country
Australia
Facility Name
Teva Investigational Site 311
City
Fitzroy
Country
Australia
Facility Name
Teva Investigational Site 301
City
Garran
Country
Australia
Facility Name
Teva Investigational Site 316
City
Geelong
Country
Australia
Facility Name
Teva Investigational Site 304
City
Hobart
Country
Australia
Facility Name
Teva Investigational Site 312
City
Kurralta Park
Country
Australia
Facility Name
Teva Investigational Site 307
City
Melbourne
Country
Australia
Facility Name
Teva Investigational Site 318
City
Parkville
Country
Australia
Facility Name
Teva Investigational Site 300
City
South Brisbane
Country
Australia
Facility Name
Teva Investigational Site 303
City
Westmead
Country
Australia
Facility Name
Teva Investigational Site 314
City
Wodonga
Country
Australia
Facility Name
Teva Investigational Site 313
City
Woodville
Country
Australia
Facility Name
Teva Investigational Site 309
City
Woolloongabba
Country
Australia
Facility Name
Teva Investigational Site 503
City
Barretos
Country
Brazil
Facility Name
Teva Investigational Site 504
City
Brasilia
Country
Brazil
Facility Name
Teva Investigational Site 506
City
Curitiba
Country
Brazil
Facility Name
Teva Investigational Site 505
City
Goiânia
Country
Brazil
Facility Name
Teva Investigational Site 502
City
Jau
Country
Brazil
Facility Name
Teva Investigational Site 509
City
Lajeado
Country
Brazil
Facility Name
Teva Investigational Site 507
City
Porto Alegre
Country
Brazil
Facility Name
Teva Investigational Site 508
City
Porto Alegre
Country
Brazil
Facility Name
Teva Investigational Site 511
City
Rio De Janeiro
Country
Brazil
Facility Name
Teva Investigational Site 500
City
Santo Andre
Country
Brazil
Facility Name
Teva Investigational Site 501
City
Sao Paulo
Country
Brazil
Facility Name
Teva Investigational Site 202
City
Barrie
Country
Canada
Facility Name
Teva Investigational Site 206
City
Calgary
Country
Canada
Facility Name
Teva Investigational Site 200
City
Halifax
Country
Canada
Facility Name
Teva Investigational Site 201
City
Ottawa
Country
Canada
Facility Name
Teva Investigational Site 203
City
Vancouver
Country
Canada
Facility Name
Teva Investigational Site 204
City
Winnipeg
Country
Canada
Facility Name
Teva Investigational Site 602
City
Aguascalientes
Country
Mexico
Facility Name
Teva Investigational Site 603
City
Hermosillo
Country
Mexico
Facility Name
Teva Investigational Site 600
City
Monterrey
Country
Mexico
Facility Name
Teva Investigational Site 601
City
Monterrey
Country
Mexico
Facility Name
Teva Investigational Site 401
City
Auckland
Country
New Zealand
Facility Name
Teva Investigational Site 405
City
Auckland
Country
New Zealand
Facility Name
Teva Investigational Site 400
City
Christchurch
Country
New Zealand
Facility Name
Teva Investigational Site 402
City
Newtown
Country
New Zealand
Facility Name
Teva Investigational Site 404
City
Palmerston North
Country
New Zealand
Facility Name
Teva Investigational Site 403
City
Takapuna
Country
New Zealand
Facility Name
Teva Investigational Site 700
City
Lima
Country
Peru
Facility Name
Teva Investigational Site 701
City
Lima
Country
Peru
Facility Name
Teva Investigational Site 704
City
Lima
Country
Peru
Facility Name
Teva Investigational Site 702
City
Miraflores
Country
Peru
Facility Name
Teva Investigational Site 703
City
Miraflores
Country
Peru

12. IPD Sharing Statement

Citations:
PubMed Identifier
24591201
Citation
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.
Results Reference
result
PubMed Identifier
30811293
Citation
Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-Line Treatment of Patients With Indolent Non-Hodgkin Lymphoma or Mantle-Cell Lymphoma With Bendamustine Plus Rituximab Versus R-CHOP or R-CVP: Results of the BRIGHT 5-Year Follow-Up Study. J Clin Oncol. 2019 Apr 20;37(12):984-991. doi: 10.1200/JCO.18.00605. Epub 2019 Feb 27.
Results Reference
derived
PubMed Identifier
26875824
Citation
Burke JM, van der Jagt RH, Kahl BS, Wood P, Hawkins TE, MacDonald D, Hertzberg M, Simpson D, Craig M, Kolibaba K, Issa S, Munteanu M, Victor TW, Flinn IW. Differences in Quality of Life Between Bendamustine-Rituximab and R-CHOP/R-CVP in Patients With Previously Untreated Advanced Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2016 Apr;16(4):182-190.e1. doi: 10.1016/j.clml.2016.01.001. Epub 2016 Jan 15.
Results Reference
derived

Learn more about this trial

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

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