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Completed

NCT Number: 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

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).

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Key information

Conditions

Non-Hodgkin's Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Mantle Cell Lymphoma Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Teva Investigational Site 315, Perth, Western Australia, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • 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.

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.

Treatment and study plan

Bendamustine

Drug

Other names: Treakisym, Ribomustin, Levact, Treanda, SDX-105

Rituximab

Drug

Other names: Rituxan, MabThera, Zytux

Vincristine

Drug

Other names: Oncovin

Prednisone

Drug

Cyclophosphamide

Drug

Other names: Endoxan, Cytoxan, Neosar, Procytox, Revimmune

Doxorubicin

Drug

Other names: Adriamycin

Primary outcomes

  1. 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.

Secondary outcomes

  1. Percentage of Participants With Overall Response at End of Treatment Period

    Time frame: 6 to 8 21 or 28-day cycles (18-32 weeks)

    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.

  2. 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

    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.

  3. 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)

    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).

  4. 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)

    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).

  5. Clinically Significant Abnormal Vital Signs

    Time frame: 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)

  6. Potentially Clinically Significant Abnormal Weight

    Time frame: Baseline, Week 32

    Participants were weighed at Baseline and at Endpoint (Week 32); those participants with an increase or decrease of >=10% were considered potentially clinically significant.

  7. Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period

    Time frame: Week 32

    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).

  8. Therapeutic Classification of Prior Medications

    Time frame: prior to start of treatment

  9. Therapeutic Classification of Concomitant Medications

    Time frame: 32 weeks

  10. 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

    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.

  11. 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

    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

  12. Kaplan-Meier Estimate for Progression-free Survival (PFS)

    Time frame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

    PFS was defined as the time from randomization to disease progression or relapse, or death from any cause, whichever occurred first.

  13. Kaplan-Meier Estimate for Event-free Survival (EFS)

    Time frame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

    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.

  14. Kaplan-Meier Estimate for Duration of Response (DOR)

    Time frame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

    DOR was defined as the time from first response (CR or PR) to disease progression or relapse, or death due to any cause.

  15. Overall Survival (OS)

    Time frame: Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)

    OS was defined as the time from randomization to death from any cause.

  16. 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

    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.

Sponsors and collaborators

Lead sponsor

Teva Branded Pharmaceutical Products R&D, Inc.

Industry

Registry information

Official study 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)

Important dates

Study start
2009
Primary completion
2012
Study completion
2012
First posted
Apr 7, 2009
Registry last updated
Feb 5, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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