Study to Assess the Effect of Treatment With Bendamustine in Combination With Rituximab on QT Interval in Patients With Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL)

NCT ID: NCT01073163

Last Updated: 2014-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2012-06-30

Brief Summary

The primary objective of this study is to assess the effect of treatment with bendamustine on cardiac repolarization as reflected by the rate-corrected QT interval by the Fridericia method (QTcF).

Detailed Description

This study was originally conducted as a substudy in a subset of patients enrolled in the phase 3 study C18083/3064/NL/MN (NCT00877006) who were randomly assigned to treatment with bendamustine in combination with rituximab (BR) and who satisfied additional eligibility criteria related to cardiac function. The objective of the substudy was to obtain results to assess the effect of bendamustine treatment on cardiac polarization and any potential changes in the QT interval (corrected by the Fridericia method [QTcF]). After a period of time, the substudy was amended to be a separate stand-alone study to ensure that an adequate number of patients were included. Patients were treated for 6, and up to 8, cycles in the stand-alone study, and efficacy and safety were also assessed. In addition, a requirement to assess the pharmacokinetics of bendamustine and rituximab when used as combination therapy was added to the objectives, to determine the potential for drug interaction between bendamustine and rituximab.

Conditions

Non-Hodgkin's Lymphoma; Mantle Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bendamustine with Rituximab

Participants were administered bendamustine intravenous (IV) infusion at 90 mg/m\^2 on Days 1 and 2 of each 28-day cycle, and rituximab IV infusion at 375 mg/m\^2 on Day 1 of each 28-day cycle.

Group Type: EXPERIMENTAL

Bendamustine

Intervention Type: DRUG

Bendamustine at 90 mg/m\^2 IV on Days 1 and 2 of a 28-day cycle.

Rituximab

Intervention Type: DRUG

Rituximab at 375 mg/m\^2 IV on Day 1 of a 28-day cycle.

Interventions

Bendamustine

Bendamustine at 90 mg/m\^2 IV on Days 1 and 2 of a 28-day cycle.

Intervention Type: DRUG

Rituximab

Rituximab at 375 mg/m\^2 IV on Day 1 of a 28-day cycle.

Intervention Type: DRUG

Other Intervention Names

Treakisym; Ribomustin; Levact; Treanda; SDX-105; Rituxan; MabThera; IDEC-C2B8

Eligibility Criteria

Inclusion Criteria

• Histopathologic confirmation of one of the following 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*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 aminotransferase (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 rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (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

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 non-Hodgkin's lymphoma (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
• The patient has a history of congenital long QT syndrome
• The patient has a history of cardiac disease with significant potential for QT prolongation
• The patient has screening electrocardiography (ECG) on Day 1 of Cycle 1 with QTcF interval >450 ms that is confirmed by a second ECG. If the QTcF interval is >450 ms on both ECGs, the ECGs will be sent to eResearch Technology, Inc. (ERT), the Central ECG Reader vendor, for an overread (with 24-hour turn around time) and ERT will make a final decision on enrollment
• The patient has serum potassium or magnesium less than the lower limit of normal

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cephalon

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sponsor's Medical Expert

Role: STUDY_DIRECTOR

Cephalon

Locations

Hematology Oncology Physicans Extenders Group

Tucson, Arizona, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

St. Jude Heritage Medical Group

Fullerton, California, United States

Comprehensive Cancer Center

Palm Springs, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

Rocky Mountain Cancer Center

Denver, Colorado, United States

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Cancer Center of Central Connecticut

Southington, Connecticut, United States

Memorial Cancer Institute

Hollywood, Florida, United States

Cancer Centers of Florida

Orlando, Florida, United States

MD Anderson Cancer Cnt Orlando

Orlando, Florida, United States

John B Amos Cancer Center

Columbus, Georgia, United States

St Francis Cancer Research Foundation

Beech Grove, Indiana, United States

Cedar Valley Medical Specialists

Waterloo, Iowa, United States

Cancer Center of Kansas

Wichita, Kansas, United States

University of Kentucky

Lexington, Kentucky, United States

LSU Health Sciences Center - Shreveport

Shreveport, Louisiana, United States

MaineGeneral Medical Center

Augusta, Maine, United States

Missouri Cancer Associates

Columbia, Missouri, United States

Kansas City Cancer Center

Kansas City, Missouri, United States

UNM Cancer Center/New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States

Interlakes Foundation, Inc

Rochester, New York, United States

SUNY Upstate / Upstate Medical University

Syracuse, New York, United States

Willamette Valley Cancer Center

Springfield, Oregon, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Pennsylvania Oncology Hematology Associates, Inc.

Philadelphia, Pennsylvania, United States

Charleston Hematology Oncology, PA

Charleston, South Carolina, United States

Sarah Cannon Cancer Center

Nashville, Tennessee, United States

Texas Oncology, P.A.

Fort Worth, Texas, United States

Cancer Care Center of South Texas

San Antonio, Texas, United States

Texas Oncology

Tyler, Texas, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Cancer Outreach Asscociates, PC

Richlands, Virginia, United States

Cancer Care Northwest-South

Spokane, Washington, United States

Northwest Cancer Specialists, PC

Vancouver, Washington, United States

West Virginia University School of Medicine

Morgantown, West Virginia, United States

The Canberra Hospital

Garran, Australian Capital Territory, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

The Queen Elizabeth Hospital

Woodville, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Countries

United States; Australia; Canada

Other Identifiers

C18083/3070

Identifier Type: -

Identifier Source: org_study_id