Non-Hodgkin's LymphomaPhase 3NCT00877006
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
A Phase 3 study testing bendamustine, rituximab and vincristine in people with Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma, run by Teva Branded Pharmaceutical Products R&D, Inc. at 128 sites in 7 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma
- What is being tested?
- bendamustine, rituximab and vincristine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 447 participants
- Where
- 128 sitesin 7 countries
- Study dates
- 30 Apr 2009to 31 Mar 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
128 sites in 7 countries.
128 sites in 7 countries
United States79 sites
Teva Investigational Site 18
Abingdon, Virginia
Teva Investigational Site 46
Albuquerque, New Mexico
Teva Investigational Site 154
Arlington, Texas
Teva Investigational Site 158
Arlington, Texas
Teva Investigational Site 72
Augusta, Georgia
Teva Investigational Site 43
Augusta, Maine
Teva Investigational Site 15
Aurora, Colorado
Teva Investigational Site 24
Beech Grove, Indiana
Teva Investigational Site 59
Bethlehem, Pennsylvania
Teva Investigational Site 49
Centralia, Illinois
Teva Investigational Site 25
Charleston, South Carolina
Teva Investigational Site 17
Charlotte, North Carolina
Teva Investigational Site 35
Charlottesville, Virginia
Teva Investigational Site 56
Chattanooga, Tennessee
Teva Investigational Site 48
Chicago, Illinois
Teva Investigational Site 9
Chicago, Illinois
Teva Investigational Site 34
Cincinnati, Ohio
Teva Investigational Site 60
Cincinnati, Ohio
Teva Investigational Site 28
Cleveland, Ohio
Teva Investigational Site 162
Columbia, Missouri
Teva Investigational Site 71
Columbia, South Carolina
Teva Investigational Site 50
Columbus, Georgia
Teva Investigational Site 11
Corona, California
Teva Investigational Site 44
Danville, Pennsylvania
Teva Investigational Site 155
Denver, Colorado
Teva Investigational Site 22
Duluth, Minnesota
Teva Investigational Site 151
Durham, North Carolina
Teva Investigational Site 6
El Paso, Texas
Teva Investigational Site 39
Fargo, North Dakota
Teva Investigational Site 5
Fort Collins, Colorado
Teva Investigational Site 58
Fort Myers, Florida
Teva Investigational Site 161
Fort Worth, Texas
Teva Investigational Site 21
Fountain Valley, California
Teva Investigational Site 52
Fountain Valley, California
Teva Investigational Site 64
Fullerton, California
Teva Investigational Site 38
Hollywood, Florida
Teva Investigational Site 152
Indianapolis, Indiana
Teva Investigational Site 31
Iowa City, Iowa
Teva Investigational Site 23
Jacksonville, Florida
Teva Investigational Site 157
Kansas City, Missouri
Teva Investigational Site 65
Lake Worth, Florida
Teva Investigational Site 33
Lexington, Kentucky
Teva Investigational Site 167
Little Rock, Arkansas
Teva Investigational Site 40
Los Angeles, California
Teva Investigational Site 53
Los Angeles, California
Teva Investigational Site 74
Lowell, Massachusetts
Teva Investigational Site 73
Macon, Georgia
Teva Investigational Site 41
Madison, Wisconsin
Teva Investigational Site 156
Miami, Florida
Teva Investigational Site 66
Morgantown, West Virginia
Teva Investigational Site 29
Morristown, New Jersey
Teva Investigational Site 30
Nashville, Tennessee
Teva Investigational Site 70
New Britain, Connecticut
Teva Investigational Site 164
Norfolk, Virginia
Teva Investigational Site 14
Normal, Illinois
Teva Investigational Site 37
Norwalk, Connecticut
Teva Investigational Site 160
Orlando, Florida
Teva Investigational Site 68
Orlando, Florida
Teva Investigational Site 3
Philadelphia, Pennsylvania
Teva Investigational Site 13
Pittsburgh, Pennsylvania
Teva Investigational Site 7
Pottstown, Pennsylvania
Teva Investigational Site 54
Richmond, Virginia
Teva Investigational Site 8
Rochester, New York
Teva Investigational Site 4
Saint Louis Park, Minnesota
Teva Investigational Site 2
Salt Lake City, Utah
Teva Investigational Site 159
San Antonio, Texas
Teva Investigational Site 57
San Diego, California
Teva Investigational Site 42
Seattle, Washington
Teva Investigational Site 19
Shreveport, Louisiana
Teva Investigational Site 67
Southington, Connecticut
Teva Investigational Site 150
Spokane, Washington
Teva Investigational Site 153
Springfield, Oregon
Teva Investigational Site 166
Sugar Land, Texas
Teva Investigational Site 10
Syracuse, New York
Teva Investigational Site 165
Tucson, Arizona
Teva Investigational Site 163
Vancouver, Washington
Teva Investigational Site 63
Waterloo, Iowa
Teva Investigational Site 62
Wausau, Wisconsin
Teva Investigational Site 47
Wichita, Kansas
Australia17 sites
Teva Investigational Site 305
Concord
Teva Investigational Site 317
Douglas
Teva Investigational Site 308
East Melbourne
Teva Investigational Site 310
Fitzroy
Teva Investigational Site 311
Fitzroy
Teva Investigational Site 301
Garran
Teva Investigational Site 316
Geelong
Teva Investigational Site 304
Hobart
Teva Investigational Site 312
Kurralta Park
Teva Investigational Site 307
Melbourne
Teva Investigational Site 318
Parkville
Teva Investigational Site 315
Perth, Western Australia
Teva Investigational Site 300
South Brisbane
Teva Investigational Site 303
Westmead
Teva Investigational Site 314
Wodonga
Teva Investigational Site 313
Woodville
Teva Investigational Site 309
Woolloongabba
Brazil11 sites
Teva Investigational Site 503
Barretos
Teva Investigational Site 504
Brasília
Teva Investigational Site 506
Curitiba
Teva Investigational Site 505
Goiânia
Teva Investigational Site 502
Jaú
Teva Investigational Site 509
Lajeado
Teva Investigational Site 507
Porto Alegre
Teva Investigational Site 508
Porto Alegre
Teva Investigational Site 511
Rio de Janeiro
Teva Investigational Site 500
Santo André
Teva Investigational Site 501
São Paulo
Canada6 sites
Teva Investigational Site 202
Barrie
Teva Investigational Site 206
Calgary
Teva Investigational Site 200
Halifax
Teva Investigational Site 201
Ottawa
Teva Investigational Site 203
Vancouver
Teva Investigational Site 204
Winnipeg
New Zealand6 sites
Teva Investigational Site 401
Auckland
Teva Investigational Site 405
Auckland
Teva Investigational Site 400
Christchurch
Teva Investigational Site 402
Newtown
Teva Investigational Site 404
Palmerston North
Teva Investigational Site 403
Takapuna
Peru5 sites
Teva Investigational Site 700
Lima
Teva Investigational Site 701
Lima
Teva Investigational Site 704
Lima
Teva Investigational Site 702
Miraflores
Teva Investigational Site 703
Miraflores
Mexico4 sites
Teva Investigational Site 602
Aguascalientes
Teva Investigational Site 603
Hermosillo
Teva Investigational Site 600
Monterrey
Teva Investigational Site 601
Monterrey
About this 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)
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).
- Conditions
- Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma
- Being tested
- bendamustine, rituximab, vincristine, prednisone, cyclophosphamide
- Medical subject headings
- Lymphoma, Non-Hodgkin, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bendamustineDrug
Also called Treakisym, Ribomustin, Levact, Treanda
rituximabDrug
Also called Rituxan, MabThera, Zytux
vincristineDrug
Also called Oncovin
prednisoneDrug
cyclophosphamideDrug
Also called Endoxan, Cytoxan, Neosar, Procytox
doxorubicinDrug
Also called Adriamycin
| Study group | Role | What they receive |
|---|---|---|
| Bendamustine and Rituximab (BR) | Experimental | 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 Receives: Drug: bendamustine; Drug: rituximab |
| R-CHOP/R-CVP | Active comparator | 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 Receives: Drug: rituximab; Drug: vincristine; Drug: prednisone; Drug: cyclophosphamide; Drug: doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 to 8 21 or 28-day cycles (18-32 weeks)
Secondary outcomes (16)
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.
Measured: 6 to 8 21 or 28-day cycles (18-32 weeks)
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.
Measured: 32 weeks
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).
Measured: 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)
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).
Measured: 32 weeks (conducted at screening, Day 1 of each cycle, weekly during treatment, and at the end-of-treatment visit)
Clinically Significant Abnormal Vital Signs
Measured: 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)
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.
Measured: Baseline, Week 32
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).
Measured: Week 32
Therapeutic Classification of Prior Medications
Measured: prior to start of treatment
Therapeutic Classification of Concomitant Medications
Measured: 32 weeks
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.
Measured: Day 1 (prior to treatment), 32 weeks
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
Measured: Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period
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.
Measured: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
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.
Measured: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
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.
Measured: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
Overall Survival (OS)
OS was defined as the time from randomization to death from any cause.
Measured: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
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.
Measured: Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2009 (estimated)
- Study start30 Apr 2009
- Primary completion31 Mar 2012
- Study completion31 Mar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 447 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sponsor's Medical Expert, Study director, Cephalon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00877006
- Sponsor's protocol ID
- C18083/3064/NL/MN
- Status last verified
- Jan 2018
- First submitted
- 3 Apr 2009
- Last updated
- 5 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 24591201Flinn 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.
PubMed 30811293Burke 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.
PubMed 26875824
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00877006
- Acronym / sponsor ID
- C18083/3064/NL/MN
- Conditions
- Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 447 participants (actual)
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Apr 2009
- Primary completion
- 31 Mar 2012 (actual)
- Study completion
- 31 Mar 2012 (actual)
- First posted
- 7 Apr 2009 (estimated)
- Results
- Posted 28 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bendamustine and Rituximab (BR) | Experimental | Drug: bendamustine, Drug: rituximabParticipants 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 |
| R-CHOP/R-CVP | Active comparator | Drug: rituximab, Drug: vincristine, Drug: prednisone, Drug: cyclophosphamide, Drug: doxorubicinParticipants 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- 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):
- Meets one of the following need-for-treatment criteria (with the exception of mantle cell lymphoma for which treatment is indicated):
- 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:
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bendamustineAlso: Treakisym, Ribomustin, Levact, Treanda | Drug | Bendamustine and Rituximab (BR) |
| rituximabAlso: Rituxan, MabThera, Zytux | Drug | Bendamustine and Rituximab (BR), R-CHOP/R-CVP |
| vincristineAlso: Oncovin | Drug | R-CHOP/R-CVP |
| prednisone | Drug | R-CHOP/R-CVP |
| cyclophosphamideAlso: Endoxan, Cytoxan, Neosar, Procytox | Drug | R-CHOP/R-CVP |
| doxorubicinAlso: Adriamycin | Drug | R-CHOP/R-CVP |
Primary outcome
Percentage of Participants With Complete Response (CR) at End of Treatment Period
Time frame: 6 to 8 21 or 28-day cycles (18-32 weeks)
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.
16 secondary outcomes
Percentage of Participants With Overall Response at End of Treatment Period
Time frame: 6 to 8 21 or 28-day cycles (18-32 weeks)
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
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)
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)
Clinically Significant Abnormal Vital Signs
Time frame: 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)
Potentially Clinically Significant Abnormal Weight
Time frame: Baseline, Week 32
Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period
Time frame: Week 32
Therapeutic Classification of Prior Medications
Time frame: prior to start of treatment
Therapeutic Classification of Concomitant Medications
Time frame: 32 weeks
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)
Time frame: Day 1 (prior to treatment), 32 weeks
Participants With Disease Progression, Relapse or Death At the End of the Treatment Period or the Long-Term Follow-up Period
Time frame: Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period
Kaplan-Meier Estimate for Progression-free Survival (PFS)
Time frame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
Kaplan-Meier Estimate for Event-free Survival (EFS)
Time frame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
Kaplan-Meier Estimate for Duration of Response (DOR)
Time frame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
Overall Survival (OS)
Time frame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)
Participants Who Died At the End of the Treatment Period or the Long-Term Follow-up Period
Time frame: Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24591201Flinn 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.
- Derived from this study: PubMed 30811293Flinn 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.
- Derived from this study: PubMed 26875824Burke 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sponsor's Medical Expert study director
Cephalon
128 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing bendamustine, rituximab and vincristine in people with Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma, run by Teva Branded Pharmaceutical Products R&D, Inc. at 128 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 128 sites in United States, Australia, Brazil, Canada, New Zealand and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Complete Response (CR) at End of Treatment Period (time frame: 6 to 8 21 or 28-day cycles (18-32 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00877006, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2018.