Clinical trial NCT00877006: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Hodgkin's Lymphoma
Mantle Cell Lymphoma
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2009-04-07
Enrollment: 447
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Key Inclusion Criteria:

* Histopathologic confirmation of one of the following cluster of differentiation antigen 20 positive (CD20+) B-cell non-Hodgkin's lymphomas (tissue diagnostic procedures must be performed within 6 months of study entry and with biopsy material available for review):

  * follicular lymphoma (NCI CTCAE grade 1 or 2)
  * immunoplasmacytoma/immunocytoma (Waldenstrom's macroglobulinemia)
  * splenic marginal zone B-cell lymphoma
  * extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tumor (MALT) type
  * nodal marginal zone B-cell lymphoma
  * mantle cell lymphoma
* Meets one of the following need-for-treatment criteria (with the exception of mantle cell lymphoma for which treatment is indicated):

  * presence of at least one of the following B-symptoms:

    1. fever (\>38ºC) of unclear etiology
    2. night sweats
    3. weight loss of greater than 10% within the prior 6 months
  * large tumor mass (bulky disease)
  * presence of lymphoma-related complications, including narrowing of ureters or bile ducts, tumor-related compression of a vital organ, lymphoma-induced pain, cytopenias related to lymphoma/leukemia, splenomegaly, pleural effusions, or ascites
  * hyperviscosity syndrome due to monoclonal gammopathy
* CD20+ B cells in lymph node biopsy or other lymphoma pathology specimen.
* No prior treatment (patients on "watch and wait" may enter the study if a recent biopsy \[obtained within the last 6 months\] is available)
* Adequate hematologic function (unless abnormalities related to lymphoma infiltration of the bone marrow or hypersplenism due to lymphoma) as follows:

  * hemoglobin of \>= 10.0 g/dL
  * absolute neutrophil count (ANC) \>=1.5\*10\^9/L
  * platelet count \>=100\*10\^9/L
* Bidimensionally measurable disease (field not previously radiated)
* Able to provide written informed consent
* Eastern Cooperative Oncology Group (ECOG) Performance Status \<=2
* Estimated life expectancy \>=6 months
* Serum creatinine of \<=2.0 mg/dL or creatinine clearance \>=50 mL/min
* Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤2.5\*upper limit of normal (ULN), and alkaline phosphatase and total bilirubin within normal limits
* Left ventricular ejection fraction (LVEF) \>= 50% by multiple gated acquisition scan (MUGA) or cardiac echocardiogram (ECHO), prior for any patient to be treated with R-CHOP
* A medically accepted method of contraception to be used by women of childbearing potential (not surgically sterile or at least 12 months naturally postmenopausal)
* Men capable of producing offspring and not surgically sterile must practice abstinence or use a barrier method of birth control.

Key Exclusion Criteria:

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

Primary outcomes:
measure: Percentage of Participants With Complete Response (CR) at End of Treatment Period
timeFrame: 6 to 8 21 or 28-day cycles (18-32 weeks)
Secondary outcomes:
measure: Percentage of Participants With Overall Response at End of Treatment Period
timeFrame: 6 to 8 21 or 28-day cycles (18-32 weeks)
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period
timeFrame: 32 weeks
measure: Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results
timeFrame: 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)
measure: Worst Overall CTCAE Grade for Hematology Laboratory Test Results
timeFrame: 32 weeks (conducted at screening, Day 1 of each cycle, weekly during treatment, and at the end-of-treatment visit)
measure: Clinically Significant Abnormal Vital Signs
timeFrame: 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)
measure: Potentially Clinically Significant Abnormal Weight
timeFrame: Baseline, Week 32
measure: Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period
timeFrame: Week 32
measure: Therapeutic Classification of Prior Medications
timeFrame: prior to start of treatment
measure: Therapeutic Classification of Concomitant Medications
timeFrame: 32 weeks
measure: 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)
timeFrame: Day 1 (prior to treatment), 32 weeks
measure: Participants With Disease Progression, Relapse or Death At the End of the Treatment Period or the Long-Term Follow-up Period
timeFrame: Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period
measure: Kaplan-Meier Estimate for Progression-free Survival (PFS)
timeFrame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
measure: Kaplan-Meier Estimate for Event-free Survival (EFS)
timeFrame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
measure: Kaplan-Meier Estimate for Duration of Response (DOR)
timeFrame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
measure: Overall Survival (OS)
timeFrame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
measure: Participants Who Died At the End of the Treatment Period or the Long-Term Follow-up Period
timeFrame: Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Teva Investigational Site 165
state: Arizona
city: Little Rock
country: United States
facility: Teva Investigational Site 167
state: Arkansas
city: Corona
country: United States
facility: Teva Investigational Site 11
state: California
city: Fountain Valley
country: United States
facility: Teva Investigational Site 21
state: California
city: Fountain Valley
country: United States
facility: Teva Investigational Site 52
state: California
city: Fullerton
country: United States
facility: Teva Investigational Site 64
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 40
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 53
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 57
state: California
city: Aurora
country: United States
facility: Teva Investigational Site 15
state: Colorado
city: Denver
country: United States
facility: Teva Investigational Site 155
state: Colorado
city: Fort Collins
country: United States
facility: Teva Investigational Site 5
state: Colorado
city: New Britain
country: United States
facility: Teva Investigational Site 70
state: Connecticut
city: Norwalk
country: United States
facility: Teva Investigational Site 37
state: Connecticut
city: Southington
country: United States
facility: Teva Investigational Site 67
state: Connecticut
city: Fort Myers
country: United States
facility: Teva Investigational Site 58
state: Florida
city: Hollywood
country: United States
facility: Teva Investigational Site 38
state: Florida
city: Jacksonville
country: United States
facility: Teva Investigational Site 23
state: Florida
city: Lake Worth
country: United States
facility: Teva Investigational Site 65
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 156
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 160
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 68
state: Florida
city: Augusta
country: United States
facility: Teva Investigational Site 72
state: Georgia
city: Columbus
country: United States
facility: Teva Investigational Site 50
state: Georgia
city: Macon
country: United States
facility: Teva Investigational Site 73
state: Georgia
city: Centralia
country: United States
facility: Teva Investigational Site 49
state: Illinois
city: Chicago
country: United States
facility: Teva Investigational Site 48
state: Illinois
city: Chicago
country: United States
facility: Teva Investigational Site 9
state: Illinois
city: Normal
country: United States
facility: Teva Investigational Site 14
state: Illinois
city: Beech Grove
country: United States
facility: Teva Investigational Site 24
state: Indiana
city: Indianapolis
country: United States
facility: Teva Investigational Site 152
state: Indiana
city: Iowa City
country: United States
facility: Teva Investigational Site 31
state: Iowa
city: Waterloo
country: United States
facility: Teva Investigational Site 63
state: Iowa
city: Wichita
country: United States
facility: Teva Investigational Site 47
state: Kansas
city: Lexington
country: United States
facility: Teva Investigational Site 33
state: Kentucky
city: Shreveport
country: United States
facility: Teva Investigational Site 19
state: Louisiana
city: Augusta
country: United States
facility: Teva Investigational Site 43
state: Maine
city: Lowell
country: United States
facility: Teva Investigational Site 74
state: Massachusetts
city: Duluth
country: United States
facility: Teva Investigational Site 22
state: Minnesota
city: Saint Louis Park
country: United States
facility: Teva Investigational Site 4
state: Minnesota
city: Columbia
country: United States
facility: Teva Investigational Site 162
state: Missouri
city: Kansas City
country: United States
facility: Teva Investigational Site 157
state: Missouri
city: Morristown
country: United States
facility: Teva Investigational Site 29
state: New Jersey
city: Albuquerque
country: United States
facility: Teva Investigational Site 46
state: New Mexico
city: Rochester
country: United States
facility: Teva Investigational Site 8
state: New York
city: Syracuse
country: United States
facility: Teva Investigational Site 10
state: New York
city: Charlotte
country: United States
facility: Teva Investigational Site 17
state: North Carolina
city: Durham
country: United States
facility: Teva Investigational Site 151
state: North Carolina
city: Fargo
country: United States
facility: Teva Investigational Site 39
state: North Dakota
city: Cincinnati
country: United States
facility: Teva Investigational Site 34
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 60
state: Ohio
city: Cleveland
country: United States
facility: Teva Investigational Site 28
state: Ohio
city: Springfield
country: United States
facility: Teva Investigational Site 153
state: Oregon
city: Bethlehem
country: United States
facility: Teva Investigational Site 59
state: Pennsylvania
city: Danville
country: United States
facility: Teva Investigational Site 44
state: Pennsylvania
city: Philadelphia
country: United States
facility: Teva Investigational Site 3
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Teva Investigational Site 13
state: Pennsylvania
city: Pottstown
country: United States
facility: Teva Investigational Site 7
state: Pennsylvania
city: Charleston
country: United States
facility: Teva Investigational Site 25
state: South Carolina
city: Columbia
country: United States
facility: Teva Investigational Site 71
state: South Carolina
city: Chattanooga
country: United States
facility: Teva Investigational Site 56
state: Tennessee
city: Nashville
country: United States
facility: Teva Investigational Site 30
state: Tennessee
city: Arlington
country: United States
facility: Teva Investigational Site 154
state: Texas
city: Arlington
country: United States
facility: Teva Investigational Site 158
state: Texas
city: El Paso
country: United States
facility: Teva Investigational Site 6
state: Texas
city: Fort Worth
country: United States
facility: Teva Investigational Site 161
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 159
state: Texas
city: Sugar Land
country: United States
facility: Teva Investigational Site 166
state: Texas
city: Salt Lake City
country: United States
facility: Teva Investigational Site 2
state: Utah
city: Abingdon
country: United States
facility: Teva Investigational Site 18
state: Virginia
city: Charlottesville
country: United States
facility: Teva Investigational Site 35
state: Virginia
city: Norfolk
country: United States
facility: Teva Investigational Site 164
state: Virginia
city: Richmond
country: United States
facility: Teva Investigational Site 54
state: Virginia
city: Seattle
country: United States
facility: Teva Investigational Site 42
state: Washington
city: Spokane
country: United States
facility: Teva Investigational Site 150
state: Washington
city: Vancouver
country: United States
facility: Teva Investigational Site 163
state: Washington
city: Morgantown
country: United States
facility: Teva Investigational Site 66
state: West Virginia
city: Madison
country: United States
facility: Teva Investigational Site 41
state: Wisconsin
city: Wausau
country: United States
facility: Teva Investigational Site 62
state: Wisconsin
city: Perth
country: Australia
facility: Teva Investigational Site 315
state: Western Australia
city: Concord
country: Australia
facility: Teva Investigational Site 305
city: Douglas
country: Australia
facility: Teva Investigational Site 317
city: East Melbourne
country: Australia
facility: Teva Investigational Site 308
city: Fitzroy
country: Australia
facility: Teva Investigational Site 310
city: Fitzroy
country: Australia
facility: Teva Investigational Site 311
city: Garran
country: Australia
facility: Teva Investigational Site 301
city: Geelong
country: Australia
facility: Teva Investigational Site 316
city: Hobart
country: Australia
facility: Teva Investigational Site 304
city: Kurralta Park
country: Australia
facility: Teva Investigational Site 312
city: Melbourne
country: Australia
facility: Teva Investigational Site 307
city: Parkville
country: Australia
facility: Teva Investigational Site 318
city: South Brisbane
country: Australia
facility: Teva Investigational Site 300
city: Westmead
country: Australia
facility: Teva Investigational Site 303
city: Wodonga
country: Australia
facility: Teva Investigational Site 314
city: Woodville
country: Australia
facility: Teva Investigational Site 313
city: Woolloongabba
country: Australia
facility: Teva Investigational Site 309
city: Barretos
country: Brazil
facility: Teva Investigational Site 503
city: Brasilia
country: Brazil
facility: Teva Investigational Site 504
city: Curitiba
country: Brazil
facility: Teva Investigational Site 506
city: Goiânia
country: Brazil
facility: Teva Investigational Site 505
city: Jau
country: Brazil
facility: Teva Investigational Site 502
city: Lajeado
country: Brazil
facility: Teva Investigational Site 509
city: Porto Alegre
country: Brazil
facility: Teva Investigational Site 507
city: Porto Alegre
country: Brazil
facility: Teva Investigational Site 508
city: Rio De Janeiro
country: Brazil
facility: Teva Investigational Site 511
city: Santo Andre
country: Brazil
facility: Teva Investigational Site 500
city: Sao Paulo
country: Brazil
facility: Teva Investigational Site 501
city: Barrie
country: Canada
facility: Teva Investigational Site 202
city: Calgary
country: Canada
facility: Teva Investigational Site 206
city: Halifax
country: Canada
facility: Teva Investigational Site 200
city: Ottawa
country: Canada
facility: Teva Investigational Site 201
city: Vancouver
country: Canada
facility: Teva Investigational Site 203
city: Winnipeg
country: Canada
facility: Teva Investigational Site 204
city: Aguascalientes
country: Mexico
facility: Teva Investigational Site 602
city: Hermosillo
country: Mexico
facility: Teva Investigational Site 603
city: Monterrey
country: Mexico
facility: Teva Investigational Site 600
city: Monterrey
country: Mexico
facility: Teva Investigational Site 601
city: Auckland
country: New Zealand
facility: Teva Investigational Site 401
city: Auckland
country: New Zealand
facility: Teva Investigational Site 405
city: Christchurch
country: New Zealand
facility: Teva Investigational Site 400
city: Newtown
country: New Zealand
facility: Teva Investigational Site 402
city: Palmerston North
country: New Zealand
facility: Teva Investigational Site 404
city: Takapuna
country: New Zealand
facility: Teva Investigational Site 403
city: Lima
country: Peru
facility: Teva Investigational Site 700
city: Lima
country: Peru
facility: Teva Investigational Site 701
city: Lima
country: Peru
facility: Teva Investigational Site 704
city: Miraflores
country: Peru
facility: Teva Investigational Site 702
city: Miraflores
country: Peru
facility: Teva Investigational Site 703
Study officials:
affiliation: Cephalon
name: Sponsor's Medical Expert
role: STUDY_DIRECTOR
References:
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.
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.
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.