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

NCT ID: NCT00877006

Last Updated: 2018-02-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

447 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-30

Study Completion Date

2012-03-31

Brief Summary

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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).

Detailed Description

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Conditions

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Non-Hodgkin's Lymphoma Mantle Cell Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

bendamustine

Intervention Type DRUG

rituximab

Intervention Type DRUG

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

Group Type ACTIVE_COMPARATOR

rituximab

Intervention Type DRUG

vincristine

Intervention Type DRUG

prednisone

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

doxorubicin

Intervention Type DRUG

Interventions

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bendamustine

Intervention Type DRUG

rituximab

Intervention Type DRUG

vincristine

Intervention Type DRUG

prednisone

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

doxorubicin

Intervention Type DRUG

Other Intervention Names

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Treakisym Ribomustin Levact Treanda SDX-105 Rituxan MabThera Zytux Oncovin Endoxan Cytoxan Neosar Procytox Revimmune Adriamycin

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sponsor's Medical Expert

Role: STUDY_DIRECTOR

Cephalon

Locations

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Teva Investigational Site 165

Tucson, Arizona, United States

Site Status

Teva Investigational Site 167

Little Rock, Arkansas, United States

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Teva Investigational Site 11

Corona, California, United States

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Teva Investigational Site 21

Fountain Valley, California, United States

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Teva Investigational Site 52

Fountain Valley, California, United States

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Teva Investigational Site 64

Fullerton, California, United States

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Teva Investigational Site 40

Los Angeles, California, United States

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Teva Investigational Site 53

Los Angeles, California, United States

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Teva Investigational Site 57

San Diego, California, United States

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Teva Investigational Site 15

Aurora, Colorado, United States

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Teva Investigational Site 155

Denver, Colorado, United States

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Teva Investigational Site 5

Fort Collins, Colorado, United States

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Teva Investigational Site 70

New Britain, Connecticut, United States

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Teva Investigational Site 37

Norwalk, Connecticut, United States

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Teva Investigational Site 67

Southington, Connecticut, United States

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Teva Investigational Site 58

Fort Myers, Florida, United States

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Teva Investigational Site 38

Hollywood, Florida, United States

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Teva Investigational Site 23

Jacksonville, Florida, United States

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Teva Investigational Site 65

Lake Worth, Florida, United States

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Teva Investigational Site 156

Miami, Florida, United States

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Teva Investigational Site 160

Orlando, Florida, United States

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Teva Investigational Site 68

Orlando, Florida, United States

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Teva Investigational Site 72

Augusta, Georgia, United States

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Teva Investigational Site 50

Columbus, Georgia, United States

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Teva Investigational Site 73

Macon, Georgia, United States

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Teva Investigational Site 49

Centralia, Illinois, United States

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Teva Investigational Site 48

Chicago, Illinois, United States

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Teva Investigational Site 9

Chicago, Illinois, United States

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Teva Investigational Site 14

Normal, Illinois, United States

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Teva Investigational Site 24

Beech Grove, Indiana, United States

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Teva Investigational Site 152

Indianapolis, Indiana, United States

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Teva Investigational Site 31

Iowa City, Iowa, United States

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Teva Investigational Site 63

Waterloo, Iowa, United States

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Teva Investigational Site 47

Wichita, Kansas, United States

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Teva Investigational Site 33

Lexington, Kentucky, United States

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Teva Investigational Site 19

Shreveport, Louisiana, United States

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Teva Investigational Site 43

Augusta, Maine, United States

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Teva Investigational Site 74

Lowell, Massachusetts, United States

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Teva Investigational Site 22

Duluth, Minnesota, United States

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Teva Investigational Site 4

Saint Louis Park, Minnesota, United States

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Teva Investigational Site 162

Columbia, Missouri, United States

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Teva Investigational Site 157

Kansas City, Missouri, United States

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Teva Investigational Site 29

Morristown, New Jersey, United States

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Teva Investigational Site 46

Albuquerque, New Mexico, United States

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Teva Investigational Site 8

Rochester, New York, United States

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Teva Investigational Site 10

Syracuse, New York, United States

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Teva Investigational Site 17

Charlotte, North Carolina, United States

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Teva Investigational Site 151

Durham, North Carolina, United States

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Teva Investigational Site 39

Fargo, North Dakota, United States

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Teva Investigational Site 34

Cincinnati, Ohio, United States

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Teva Investigational Site 60

Cincinnati, Ohio, United States

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Teva Investigational Site 28

Cleveland, Ohio, United States

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Teva Investigational Site 153

Springfield, Oregon, United States

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Teva Investigational Site 59

Bethlehem, Pennsylvania, United States

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Teva Investigational Site 44

Danville, Pennsylvania, United States

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Teva Investigational Site 3

Philadelphia, Pennsylvania, United States

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Teva Investigational Site 13

Pittsburgh, Pennsylvania, United States

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Teva Investigational Site 7

Pottstown, Pennsylvania, United States

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Teva Investigational Site 25

Charleston, South Carolina, United States

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Teva Investigational Site 71

Columbia, South Carolina, United States

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Teva Investigational Site 56

Chattanooga, Tennessee, United States

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Teva Investigational Site 30

Nashville, Tennessee, United States

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Teva Investigational Site 154

Arlington, Texas, United States

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Teva Investigational Site 158

Arlington, Texas, United States

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Teva Investigational Site 6

El Paso, Texas, United States

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Teva Investigational Site 161

Fort Worth, Texas, United States

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Teva Investigational Site 159

San Antonio, Texas, United States

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Teva Investigational Site 166

Sugar Land, Texas, United States

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Teva Investigational Site 2

Salt Lake City, Utah, United States

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Teva Investigational Site 18

Abingdon, Virginia, United States

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Teva Investigational Site 35

Charlottesville, Virginia, United States

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Teva Investigational Site 164

Norfolk, Virginia, United States

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Teva Investigational Site 54

Richmond, Virginia, United States

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Teva Investigational Site 42

Seattle, Washington, United States

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Teva Investigational Site 150

Spokane, Washington, United States

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Teva Investigational Site 163

Vancouver, Washington, United States

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Teva Investigational Site 66

Morgantown, West Virginia, United States

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Teva Investigational Site 41

Madison, Wisconsin, United States

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Teva Investigational Site 62

Wausau, Wisconsin, United States

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Teva Investigational Site 315

Perth, Western Australia, Australia

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Teva Investigational Site 305

Concord, , Australia

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Teva Investigational Site 317

Douglas, , Australia

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Teva Investigational Site 308

East Melbourne, , Australia

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Teva Investigational Site 310

Fitzroy, , Australia

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Teva Investigational Site 311

Fitzroy, , Australia

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Teva Investigational Site 301

Garran, , Australia

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Teva Investigational Site 316

Geelong, , Australia

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Teva Investigational Site 304

Hobart, , Australia

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Teva Investigational Site 312

Kurralta Park, , Australia

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Teva Investigational Site 307

Melbourne, , Australia

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Teva Investigational Site 318

Parkville, , Australia

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Teva Investigational Site 300

South Brisbane, , Australia

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Teva Investigational Site 303

Westmead, , Australia

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Teva Investigational Site 314

Wodonga, , Australia

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Teva Investigational Site 313

Woodville, , Australia

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Teva Investigational Site 309

Woolloongabba, , Australia

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Teva Investigational Site 503

Barretos, , Brazil

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Teva Investigational Site 504

Brasília, , Brazil

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Teva Investigational Site 506

Curitiba, , Brazil

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Teva Investigational Site 505

Goiânia, , Brazil

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Teva Investigational Site 502

Jaú, , Brazil

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Teva Investigational Site 509

Lajeado, , Brazil

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Teva Investigational Site 507

Porto Alegre, , Brazil

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Teva Investigational Site 508

Porto Alegre, , Brazil

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Teva Investigational Site 511

Rio de Janeiro, , Brazil

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Teva Investigational Site 500

Santo André, , Brazil

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Teva Investigational Site 501

São Paulo, , Brazil

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Teva Investigational Site 202

Barrie, , Canada

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Teva Investigational Site 206

Calgary, , Canada

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Teva Investigational Site 200

Halifax, , Canada

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Teva Investigational Site 201

Ottawa, , Canada

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Teva Investigational Site 203

Vancouver, , Canada

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Teva Investigational Site 204

Winnipeg, , Canada

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Teva Investigational Site 602

Aguascalientes, , Mexico

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Teva Investigational Site 603

Hermosillo, , Mexico

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Teva Investigational Site 600

Monterrey, , Mexico

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Teva Investigational Site 601

Monterrey, , Mexico

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Teva Investigational Site 401

Auckland, , New Zealand

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Teva Investigational Site 405

Auckland, , New Zealand

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Teva Investigational Site 400

Christchurch, , New Zealand

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Teva Investigational Site 402

Newtown, , New Zealand

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Teva Investigational Site 404

Palmerston North, , New Zealand

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Teva Investigational Site 403

Takapuna, , New Zealand

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Teva Investigational Site 700

Lima, , Peru

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Teva Investigational Site 701

Lima, , Peru

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Teva Investigational Site 704

Lima, , Peru

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Teva Investigational Site 702

Miraflores, , Peru

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Teva Investigational Site 703

Miraflores, , Peru

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Countries

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United States Australia Brazil Canada Mexico New Zealand Peru

References

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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.

Reference Type RESULT
PMID: 24591201 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30811293 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26875824 (View on PubMed)

Other Identifiers

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C18083/3064/NL/MN

Identifier Type: -

Identifier Source: org_study_id

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