Overview

This trial is active, not recruiting.

Conditions non-hodgkin's lymphoma, mantle cell lymphoma
Treatments bendamustine, rituximab, vincristine, prednisone, cyclophosphamide, doxorubicin
Phase phase 3
Target CD20
Sponsor Teva Branded Pharmaceutical Products, R&D Inc.
Start date April 2009
End date March 2012
Trial size 447 participants
Trial identifier NCT00877006, C18083/3064/NL/MN

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(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
bendamustine Treakisym
rituximab Rituxan
(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
rituximab Rituxan
vincristine Oncovin
prednisone
cyclophosphamide Endoxan
doxorubicin Adriamycin

Primary Outcomes

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)

Secondary Outcomes

Measure
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
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
Progression-free Survival and Event-free Survival at End of Follow-up
time frame: 286 weeks (5.5 years)
Overall Survival at End of Follow-up
time frame: 286 weeks (5.5 years)
Median Duration of Response at End of Follow-up
time frame: 286 weeks (5.5 years)

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

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)
Trial information was received from ClinicalTrials.gov and was last updated in April 2014.
Information provided to ClinicalTrials.gov by Teva Pharmaceutical Industries.