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 ( Cephalon )
ClinicalTrials.gov Identifier:
NCT00877006
First received: April 3, 2009
Last updated: September 27, 2013
Last verified: September 2013
  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:
  • Compare the complete response (CR) rate at end of treatment of bendamustine and rituximab (BR) with either R-CVP or R-CHOP in the treatment of patients with advanced indolent non-Hodgkin's lymphoma or mantle cell lymphoma. [ Time Frame: 6-8 cycles, or 18-32 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare the Safety and Tolerability of BR and R-CVP, or R-CHOP [ Time Frame: Periodically over a 32 week period ] [ Designated as safety issue: Yes ]
  • Overall Response Rate (ORR) = Complete Remission (CR) + Partial Remission (PR) [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
  • Progression-Free Survival [ Time Frame: 286 weeks (5.5 years) ] [ Designated as safety issue: No ]
  • Quality of Life, as determined by the European Organization for Research and Treatment of Cancer (EORTC) 30-item core Quality of Life questionnaire (QLQ-C30) [ Time Frame: Periodically over a 32 week period ] [ Designated as safety issue: No ]
  • Median Durations of Responses [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]

Enrollment: 447
Study Start Date: April 2009
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bendamustine
Investigational Treatment Group (BR)
Drug: bendamustine
bendamustine at 90 mg/m2 iv on days 1 and 2
Active Comparator: R-CHOP
R-CHOP, consisting of rituximab at 375 mg/m2 iv on day 1, vincristine at 1.4 mg /m2 (up to a maximum dose of 2 mg iv) by iv on day 1, prednisone at 100 mg orally on days 1 to 5 of a 21-day cycle, doxorubicin at 50 mg/m2 by iv over 3-5 minutes on day 1, cyclophosphamide iv at 750 mg/m2 on day 1,
Drug: rituximab
rituximab at 375 mg/m2 iv on day 1 of each 28-day cycle for 6 cycles
Drug: Vincristine
vincristine 1.4 mg (up to maximum dose of 2 mg iv)
Drug: prednisone
prednisone 100mg
Drug: cyclophosphamide
cyclophosphamide 750 mg/m2 iv or 1000 mg/m2 iv
Drug: Doxorubicin
Doxorubicin 50 mg/m2 by iv
Active Comparator: R-CVP

R-CVP consisting of rituximab at 375 mg/m2 iv on day 1, vincristine at 1.4 mg /m2 (up to a maximum dose of 2 mg iv) by iv on day 1, prednisone at 100 mg orally on days 1 to 5 of a 21-day cycle, only 1 of the following doses of cyclophosphamide throughout the study:

  • cyclophosphamide at 750 mg/m2 iv on day 1 or
  • cyclophosphamide at 1000 mg/ m2 iv on day 1
Drug: rituximab
rituximab at 375 mg/m2 iv on day 1 of each 28-day cycle for 6 cycles
Drug: Vincristine
vincristine 1.4 mg (up to maximum dose of 2 mg iv)
Drug: prednisone
prednisone 100mg
Drug: cyclophosphamide
cyclophosphamide 750 mg/m2 iv or 1000 mg/m2 iv

  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 (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 (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 positive 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 x 10 9th power/L
    • platelet count >= 100 x 10 9th power/L
  • Bidimensionally measurable disease (field not previously radiated).
  • Able to provide written informed consent.
  • electrocorticogram (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 x 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, electrocardiographic 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.
  • The patient has Ann Arbor stage I disease.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00877006

  Show 114 Study Locations
Sponsors and Collaborators
Cephalon
Investigators
Study Director: Sponsor's Medical Expert Cephalon
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier: NCT00877006     History of Changes
Other Study ID Numbers: C18083/3064/NL/MN
Study First Received: April 3, 2009
Last Updated: September 27, 2013
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
Nitrogen Mustard Compounds
Bendamustine
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
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on April 22, 2014