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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier:
NCT00877006
First received: April 3, 2009
Last updated: April 29, 2014
Last verified: April 2014
  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).


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Mantle Cell Lymphoma
Drug: bendamustine
Drug: rituximab
Drug: vincristine
Drug: prednisone
Drug: cyclophosphamide
Drug: doxorubicin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • 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) ] [ 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.


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 ]

Enrollment: 447
Study Start Date: April 2009
Estimated Study Completion Date: March 2017
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: bendamustine
Other Names:
  • Treakisym
  • Ribomustin
  • Levact
  • Treanda
  • SDX-105
Drug: rituximab
Other Names:
  • Rituxan
  • MabThera
  • Zytux
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

Drug: rituximab
Other Names:
  • Rituxan
  • MabThera
  • Zytux
Drug: vincristine
Other Name: Oncovin
Drug: prednisone Drug: cyclophosphamide
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
Drug: doxorubicin
Other Name: Adriamycin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00877006

  Show 114 Study Locations
Sponsors and Collaborators
Teva Branded Pharmaceutical Products, R&D Inc.
Investigators
Study Director: Sponsor's Medical Expert Cephalon
  More Information

Publications:
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT00877006     History of Changes
Other Study ID Numbers: C18083/3064/NL/MN
Study First Received: April 3, 2009
Results First Received: March 25, 2014
Last Updated: April 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Bendamustine
Nitrogen Mustard Compounds
Liposomal doxorubicin
Doxorubicin
Prednisone
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014