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

Overview[ - collapse ][ - ]

Purpose 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).
ConditionNon-Hodgkin's Lymphoma
Mantle Cell Lymphoma
InterventionDrug: bendamustine
Drug: rituximab
Drug: vincristine
Drug: prednisone
Drug: cyclophosphamide
Drug: doxorubicin
PhasePhase 3
SponsorTeva Branded Pharmaceutical Products, R&D Inc.
Responsible PartyTeva Pharmaceutical Industries
ClinicalTrials.gov IdentifierNCT00877006
First ReceivedApril 3, 2009
Last UpdatedMarch 25, 2014
Last verifiedMarch 2014

Tracking Information[ + expand ][ + ]

First Received DateApril 3, 2009
Last Updated DateMarch 25, 2014
Start DateApril 2009
Estimated Primary Completion DateMarch 2017
Current Primary Outcome MeasuresPercentage of Participants With Complete Response (CR) at End of Treatment Period [Time Frame: 6 to 8 21 or 28-day cycles (18-32 weeks)] [Designated as safety issue: No]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.
Current Secondary Outcome Measures
  • Percentage of Participants With Overall Response at End of Treatment Period [Time Frame: 6 to 8 21 or 28-day cycles (18-32 weeks)] [Designated as safety issue: No]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 [Time Frame: 32 weeks] [Designated as safety issue: Yes]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 [Time Frame: 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)] [Designated as safety issue: Yes]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 [Time Frame: 32 weeks (conducted at screening, Day 1 of each cycle, weekly during treatment, and at the end-of-treatment visit)] [Designated as safety issue: No]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 [Time Frame: 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)] [Designated as safety issue: Yes]
  • Potentially Clinically Significant Abnormal Weight [Time Frame: Baseline, Week 32] [Designated as safety issue: Yes]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 [Time Frame: Week 32] [Designated as safety issue: Yes]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 [Time Frame: prior to start of treatment] [Designated as safety issue: Yes]
  • Therapeutic Classification of Concomitant Medications [Time Frame: 32 weeks] [Designated as safety issue: Yes]
  • European Organization for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ-C30) at End of Treatment [Time Frame: 32 weeks] [Designated as safety issue: No]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). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning.
  • Progression-free Survival and Event-free Survival at End of Follow-up [Time Frame: 286 weeks (5.5 years)] [Designated as safety issue: No]
  • Overall Survival at End of Follow-up [Time Frame: 286 weeks (5.5 years)] [Designated as safety issue: Yes]
  • Median Duration of Response at End of Follow-up [Time Frame: 286 weeks (5.5 years)] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleStudy 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 TitleAn 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)
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).
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Non-Hodgkin's Lymphoma
  • Mantle Cell Lymphoma
InterventionDrug: bendamustine
Other Names:
  • Treakisym
  • Ribomustin
  • Levact
  • Treanda
  • SDX-105
Drug: rituximab
Other Names:
  • Rituxan
  • MabThera
  • Zytux
Drug: vincristine
Other Names:
OncovinDrug: prednisone
Drug: cyclophosphamide
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
Drug: doxorubicin
Other Names:
Adriamycin
Study Arm (s)
  • 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

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment447
Estimated Completion DateMarch 2017
Estimated Primary Completion DateMarch 2012
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.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Australia, Brazil, Canada, Mexico, New Zealand, Peru

Administrative Information[ + expand ][ + ]

NCT Number NCT00877006
Other Study ID NumbersC18083/3064/NL/MN
Has Data Monitoring CommitteeYes
Information Provided ByTeva Pharmaceutical Industries
Study SponsorTeva Branded Pharmaceutical Products, R&D Inc.
CollaboratorsNot Provided
Investigators Study Director: Sponsor's Medical Expert Cephalon
Verification DateMarch 2014

Locations[ + expand ][ + ]

Teva Investigational Site 165
Tucson, Arizona, United States
Teva Investigational Site 167
Little Rock, Arkansas, United States
Teva Investigational Site 52
Fountain Valley, California, United States
Teva Investigational Site 21
Fountain Valley, California, United States
Teva Investigational Site 64
Fullerton, California, United States
Teva Investigational Site 40
Los Angeles, California, United States
Teva Investigational Site 53
Los Angeles, California, United States
Teva Investigational Site 57
San Diego, California, United States
Teva Investigational Site 15
Aurora, Colorado, United States
Teva Investigational Site 155
Denver, Colorado, United States
Teva Investigational Site 5
Fort Collins, Colorado, United States
Teva Investigational Site 70
New Britain, Connecticut, United States
Teva Investigational Site 37
Norwalk, Connecticut, United States
Teva Investigational Site 67
Southington, Connecticut, United States
Teva Investigational Site 58
Fort Myers, Florida, United States
Teva Investigational Site 38
Hollywood, Florida, United States
Teva Investigational Site 65
Lake Worth, Florida, United States
Teva Investigational Site 68
Orlando, Florida, United States
Teva Investigational Site 160
Orlando, Florida, United States
Teva Investigational Site 72
Augusta, Georgia, United States
Teva Investigational Site 50
Columbus, Georgia, United States
Teva Investigational Site 73
Macon, Georgia, United States
Teva Investigational Site 9
Chicago, Illinois, United States
Teva Investigational Site 48
Chicago, Illinois, United States
Teva Investigational Site 24
Beech Grove, Indiana, United States
Teva Investigational Site 152
Indianapolis, Indiana, United States
Teva Investigational Site 31
Iowa City, Iowa, United States
Teva Investigational Site 47
Wichita, Kansas, United States
Teva Investigational Site 33
Lexington, Kentucky, United States
Teva Investigational Site 19
Shreveport, Louisiana, United States
Teva Investigational Site 43
Augusta, Maine, United States
Teva Investigational Site 74
Lowell, Massachusetts, United States
Teva Investigational Site 22
Duluth, Minnesota, United States
Teva Investigational Site 4
St. Louis Park, Minnesota, United States
Teva Investigational Site 162
Columbia, Missouri, United States
Teva Investigational Site 157
Kansas City, Missouri, United States
Teva Investigational Site 46
Albuquerque, New Mexico, United States
Teva Investigational Site 10
Syracuse, New York, United States
Teva Investigational Site 17
Charlotte, North Carolina, United States
Teva Investigational Site 39
Fargo, North Dakota, United States
Teva Investigational Site 28
Cleveland, Ohio, United States
Teva Investigational Site 153
Springfield, Oregon, United States
Teva Investigational Site 59
Bethlehem, Pennsylvania, United States
Teva Investigational Site 44
Danville, Pennsylvania, United States
Teva Investigational Site 13
Pittsburgh, Pennsylvania, United States
Teva Investigational Site 7
Pottstown, Pennsylvania, United States
Teva Investigational Site 25
Charleston, South Carolina, United States
Teva Investigational Site 71
Columbia, South Carolina, United States
Teva Investigational Site 56
Chattanooga, Tennessee, United States
Teva Investigational Site 30
Nashville, Tennessee, United States
Teva Investigational Site 158
Arlington, Texas, United States
Teva Investigational Site 154
Arlington, Texas, United States
Teva Investigational Site 161
Fort Worth, Texas, United States
Teva Investigational Site 159
San Antonio, Texas, United States
Teva Investigational Site 166
Sugar Land, Texas, United States
Teva Investigational Site 2
Salt Lake City, Utah, United States
Teva Investigational Site 18
Abingdon, Virginia, United States
Teva Investigational Site 35
Charlottesville, Virginia, United States
Teva Investigational Site 164
Norfolk, Virginia, United States
Teva Investigational Site 54
Richmond, Virginia, United States
Teva Investigational Site 42
Seattle, Washington, United States
Teva Investigational Site 150
Spokane, Washington, United States
Teva Investigational Site 163
Vancouver, Washington, United States
Teva Investigational Site 66
Morgantown, West Virginia, United States
Teva Investigational Site 41
Madison, Wisconsin, United States
Teva Investigational Site 62
Wausau, Wisconsin, United States
Teva Investigational Site 315
Perth, Western Australia, Australia
Teva Investigational Site 305
Concord, Australia
Teva Investigational Site 317
Douglas, Australia
Teva Investigational Site 308
East Melbourne, Australia
Teva Investigational Site 310
Fitzroy, Australia
Teva Investigational Site 311
Fitzroy, Australia
Teva Investigational Site 301
Garran, Australia
Teva Investigational Site 316
Geelong, Australia
Teva Investigational Site 304
Hobart, Australia
Teva Investigational Site 312
Kurralta Park, Australia
Teva Investigational Site 307
Melbourne, Australia
Teva Investigational Site 306
North Terrace, Australia
Teva Investigational Site 318
Parkville, Australia
Teva Investigational Site 300
South Brisbane, Australia
Teva Investigational Site 303
Westmead, Australia
Teva Investigational Site 314
Wodonga, Australia
Teva Investigational Site 313
Woodville, Australia
Teva Investigational Site 309
Woolloongabba, Australia
Teva Investigational Site 503
Barretos-SP, Brazil
Teva Investigational Site 504
Brasilia, DF, Brazil
Teva Investigational Site 502
Jau, Brazil
Teva Investigational Site 509
Lajeado-RS, Brazil
Teva Investigational Site 508
Porto Alegre, Brazil
Teva Investigational Site 507
Porto Alegre, Brazil
Teva Investigational Site 511
Rio de Janeiro - RJ, Brazil
Teva Investigational Site 500
Santo Andre, Brazil
Teva Investigational Site 501
Sao Paulo, Brazil
Teva Investigational Site 202
Barrie, Canada
Teva Investigational Site 206
Calgary, Canada
Teva Investigational Site 200
Halifax, Canada
Teva Investigational Site 201
Ottawa, Canada
Teva Investigational Site 203
Vancouver, Canada
Teva Investigational Site 204
Winnipeg, Canada
Teva Investigational Site 602
Aguascalientes, Mexico
Teva Investigational Site 603
Hermosillo, Sonora, Mexico
Teva Investigational Site 601
Monterrey, Mexico
Teva Investigational Site 600
Monterrey - NL, Mexico
Teva Investigational Site 405
Auckland, New Zealand
Teva Investigational Site 401
Auckland, New Zealand
Teva Investigational Site 400
Christchurch, New Zealand
Teva Investigational Site 402
Newtown, New Zealand
Teva Investigational Site 404
Palmerston North, New Zealand
Teva Investigational Site 403
Takapuna, New Zealand
Teva Investigational Site 701
Lima, Peru
Teva Investigational Site 704
Lima, Peru
Teva Investigational Site 700
Lima, Peru
Teva Investigational Site 702
Miraflores, Peru
Teva Investigational Site 703
Miraflores, Peru