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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00877006




Registration number
NCT00877006
Ethics application status
Date submitted
3/04/2009
Date registered
7/04/2009
Date last updated
5/02/2018

Titles & IDs
Public 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
Scientific 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)
Secondary ID [1] 0 0
C18083/3064/NL/MN
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin's Lymphoma 0 0
Mantle Cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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

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
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Complete Response (CR) at End of Treatment Period
Timepoint [1] 0 0
6 to 8 21 or 28-day cycles (18-32 weeks)
Secondary outcome [1] 0 0
Percentage of Participants With Overall Response at End of Treatment Period
Timepoint [1] 0 0
6 to 8 21 or 28-day cycles (18-32 weeks)
Secondary outcome [2] 0 0
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period
Timepoint [2] 0 0
32 weeks
Secondary outcome [3] 0 0
Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results
Timepoint [3] 0 0
32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)
Secondary outcome [4] 0 0
Worst Overall CTCAE Grade for Hematology Laboratory Test Results
Timepoint [4] 0 0
32 weeks (conducted at screening, Day 1 of each cycle, weekly during treatment, and at the end-of-treatment visit)
Secondary outcome [5] 0 0
Clinically Significant Abnormal Vital Signs
Timepoint [5] 0 0
32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)
Secondary outcome [6] 0 0
Potentially Clinically Significant Abnormal Weight
Timepoint [6] 0 0
Baseline, Week 32
Secondary outcome [7] 0 0
Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period
Timepoint [7] 0 0
Week 32
Secondary outcome [8] 0 0
Therapeutic Classification of Prior Medications
Timepoint [8] 0 0
prior to start of treatment
Secondary outcome [9] 0 0
Therapeutic Classification of Concomitant Medications
Timepoint [9] 0 0
32 weeks
Secondary outcome [10] 0 0
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)
Timepoint [10] 0 0
Day 1 (prior to treatment), 32 weeks
Secondary outcome [11] 0 0
Participants With Disease Progression, Relapse or Death At the End of the Treatment Period or the Long-Term Follow-up Period
Timepoint [11] 0 0
Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period
Secondary outcome [12] 0 0
Kaplan-Meier Estimate for Progression-free Survival (PFS)
Timepoint [12] 0 0
Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
Secondary outcome [13] 0 0
Kaplan-Meier Estimate for Event-free Survival (EFS)
Timepoint [13] 0 0
Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
Secondary outcome [14] 0 0
Kaplan-Meier Estimate for Duration of Response (DOR)
Timepoint [14] 0 0
Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
Secondary outcome [15] 0 0
Overall Survival (OS)
Timepoint [15] 0 0
Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
Secondary outcome [16] 0 0
Participants Who Died At the End of the Treatment Period or the Long-Term Follow-up Period
Timepoint [16] 0 0
Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/04/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/03/2012
Sample size
Target
Accrual to date
Final
447
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Teva Investigational Site 315 - Perth
Recruitment hospital [2] 0 0
Teva Investigational Site 305 - Concord
Recruitment hospital [3] 0 0
Teva Investigational Site 317 - Douglas
Recruitment hospital [4] 0 0
Teva Investigational Site 308 - East Melbourne
Recruitment hospital [5] 0 0
Teva Investigational Site 310 - Fitzroy
Recruitment hospital [6] 0 0
Teva Investigational Site 311 - Fitzroy
Recruitment hospital [7] 0 0
Teva Investigational Site 301 - Garran
Recruitment hospital [8] 0 0
Teva Investigational Site 316 - Geelong
Recruitment hospital [9] 0 0
Teva Investigational Site 304 - Hobart
Recruitment hospital [10] 0 0
Teva Investigational Site 312 - Kurralta Park
Recruitment hospital [11] 0 0
Teva Investigational Site 307 - Melbourne
Recruitment hospital [12] 0 0
Teva Investigational Site 318 - Parkville
Recruitment hospital [13] 0 0
Teva Investigational Site 300 - South Brisbane
Recruitment hospital [14] 0 0
Teva Investigational Site 303 - Westmead
Recruitment hospital [15] 0 0
Teva Investigational Site 314 - Wodonga
Recruitment hospital [16] 0 0
Teva Investigational Site 313 - Woodville
Recruitment hospital [17] 0 0
Teva Investigational Site 309 - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Perth
Recruitment postcode(s) [2] 0 0
- Concord
Recruitment postcode(s) [3] 0 0
- Douglas
Recruitment postcode(s) [4] 0 0
- East Melbourne
Recruitment postcode(s) [5] 0 0
- Fitzroy
Recruitment postcode(s) [6] 0 0
- Garran
Recruitment postcode(s) [7] 0 0
- Geelong
Recruitment postcode(s) [8] 0 0
- Hobart
Recruitment postcode(s) [9] 0 0
- Kurralta Park
Recruitment postcode(s) [10] 0 0
- Melbourne
Recruitment postcode(s) [11] 0 0
- Parkville
Recruitment postcode(s) [12] 0 0
- South Brisbane
Recruitment postcode(s) [13] 0 0
- Westmead
Recruitment postcode(s) [14] 0 0
- Wodonga
Recruitment postcode(s) [15] 0 0
- Woodville
Recruitment postcode(s) [16] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Iowa
Country [11] 0 0
United States of America
State/province [11] 0 0
Kansas
Country [12] 0 0
United States of America
State/province [12] 0 0
Kentucky
Country [13] 0 0
United States of America
State/province [13] 0 0
Louisiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Maine
Country [15] 0 0
United States of America
State/province [15] 0 0
Massachusetts
Country [16] 0 0
United States of America
State/province [16] 0 0
Minnesota
Country [17] 0 0
United States of America
State/province [17] 0 0
Missouri
Country [18] 0 0
United States of America
State/province [18] 0 0
New Jersey
Country [19] 0 0
United States of America
State/province [19] 0 0
New Mexico
Country [20] 0 0
United States of America
State/province [20] 0 0
New York
Country [21] 0 0
United States of America
State/province [21] 0 0
North Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
North Dakota
Country [23] 0 0
United States of America
State/province [23] 0 0
Ohio
Country [24] 0 0
United States of America
State/province [24] 0 0
Oregon
Country [25] 0 0
United States of America
State/province [25] 0 0
Pennsylvania
Country [26] 0 0
United States of America
State/province [26] 0 0
South Carolina
Country [27] 0 0
United States of America
State/province [27] 0 0
Tennessee
Country [28] 0 0
United States of America
State/province [28] 0 0
Texas
Country [29] 0 0
United States of America
State/province [29] 0 0
Utah
Country [30] 0 0
United States of America
State/province [30] 0 0
Virginia
Country [31] 0 0
United States of America
State/province [31] 0 0
Washington
Country [32] 0 0
United States of America
State/province [32] 0 0
West Virginia
Country [33] 0 0
United States of America
State/province [33] 0 0
Wisconsin
Country [34] 0 0
Brazil
State/province [34] 0 0
Barretos
Country [35] 0 0
Brazil
State/province [35] 0 0
Brasilia
Country [36] 0 0
Brazil
State/province [36] 0 0
Curitiba
Country [37] 0 0
Brazil
State/province [37] 0 0
Goiânia
Country [38] 0 0
Brazil
State/province [38] 0 0
Jau
Country [39] 0 0
Brazil
State/province [39] 0 0
Lajeado
Country [40] 0 0
Brazil
State/province [40] 0 0
Porto Alegre
Country [41] 0 0
Brazil
State/province [41] 0 0
Rio De Janeiro
Country [42] 0 0
Brazil
State/province [42] 0 0
Santo Andre
Country [43] 0 0
Brazil
State/province [43] 0 0
Sao Paulo
Country [44] 0 0
Canada
State/province [44] 0 0
Barrie
Country [45] 0 0
Canada
State/province [45] 0 0
Calgary
Country [46] 0 0
Canada
State/province [46] 0 0
Halifax
Country [47] 0 0
Canada
State/province [47] 0 0
Ottawa
Country [48] 0 0
Canada
State/province [48] 0 0
Vancouver
Country [49] 0 0
Canada
State/province [49] 0 0
Winnipeg
Country [50] 0 0
Mexico
State/province [50] 0 0
Aguascalientes
Country [51] 0 0
Mexico
State/province [51] 0 0
Hermosillo
Country [52] 0 0
Mexico
State/province [52] 0 0
Monterrey
Country [53] 0 0
New Zealand
State/province [53] 0 0
Auckland
Country [54] 0 0
New Zealand
State/province [54] 0 0
Christchurch
Country [55] 0 0
New Zealand
State/province [55] 0 0
Newtown
Country [56] 0 0
New Zealand
State/province [56] 0 0
Palmerston North
Country [57] 0 0
New Zealand
State/province [57] 0 0
Takapuna
Country [58] 0 0
Peru
State/province [58] 0 0
Lima
Country [59] 0 0
Peru
State/province [59] 0 0
Miraflores

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Teva Branded Pharmaceutical Products R&D, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT00877006
Trial related presentations / publications
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.
Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-Line Treatment of Patients With Indolent Non-Hodgkin Lymphoma or Mantle-Cell Lymphoma With Bendamustine Plus Rituximab Versus R-CHOP or R-CVP: Results of the BRIGHT 5-Year Follow-Up Study. J Clin Oncol. 2019 Apr 20;37(12):984-991. doi: 10.1200/JCO.18.00605. Epub 2019 Feb 27.
Burke JM, van der Jagt RH, Kahl BS, Wood P, Hawkins TE, MacDonald D, Hertzberg M, Simpson D, Craig M, Kolibaba K, Issa S, Munteanu M, Victor TW, Flinn IW. Differences in Quality of Life Between Bendamustine-Rituximab and R-CHOP/R-CVP in Patients With Previously Untreated Advanced Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2016 Apr;16(4):182-190.e1. doi: 10.1016/j.clml.2016.01.001. Epub 2016 Jan 15.
Public notes

Contacts
Principal investigator
Name 0 0
Sponsor's Medical Expert
Address 0 0
Cephalon
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00877006