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)

NCT01073163 | Completed Phase 3 Results

• 1 other identifier: C18083/3070
• Study Type: interventional
• Target: 54
• Locations: 3 countries
• Sites: 43

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).

Conditions

Non-Hodgkin's Lymphoma; Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in QT Interval as Corrected by the Fridericia Method (QTcF) at End of Infusion

  On Day 2 of Cycle 1, three electrocardiograms (ECGs) were collected 15 minutes prior to any study drug administration. The baseline ECG interval value was obtained by averaging these 3 ECGs, and was compared to the average of the 3 ECGs taken on treatment with bendamustine at the end of the infusion.

  Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): at the end of the 30-minute infusion.

Secondary Outcomes (12)

• Mean Change From Baseline in QTcF at 1 Hour Postinfusion

  Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): 1 hour postinfusion.

• Number of Participants With QTcF New Outlier Events at End of Infusion and 1 Hour Postinfusion

  Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): at the end of the 30-minute infusion and 1 hour postinfusion.

• Number of Participants With New Onset ECG Waveform Morphological Changes

  Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): at the end of the 30-minute infusion and 1 hour postinfusion.

• Number of Participants With Treatment-Emergent Cardiac Disorders

  Adverse events were collected throughout the study and up to 30 days after the last dose of study drug. The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days.

• Change From Baseline in QTcF at Maximum Concentration (Cmax) of Bendamustine and Its Metabolites (M3 and M4)

  Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): at the end of the 30-minute infusion and 1 hour postinfusion.

Study Arms (1)

Bendamustine with Rituximab

EXPERIMENTAL

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.

Drug: Bendamustine; Drug: Rituximab

Interventions

Bendamustine DRUG

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

Also known as: Treakisym, Ribomustin, Levact, Treanda, SDX-105

Bendamustine with Rituximab

Rituximab DRUG

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

Also known as: Rituxan, MabThera, IDEC-C2B8

Bendamustine with Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cephalon: lead

Study Sites (43)

Hematology Oncology Physicans Extenders Group

Tucson, Arizona, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Location

St. Jude Heritage Medical Group

Fullerton, California, United States

Location

Comprehensive Cancer Center

Palm Springs, California, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, United States

Location

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Location

Cancer Center of Central Connecticut

Southington, Connecticut, United States

Location

Memorial Cancer Institute

Hollywood, Florida, United States

Location

Cancer Centers of Florida

Orlando, Florida, United States

Location

MD Anderson Cancer Cnt Orlando

Orlando, Florida, United States

Location

John B Amos Cancer Center

Columbus, Georgia, United States

Location

St Francis Cancer Research Foundation

Beech Grove, Indiana, United States

Location

Cedar Valley Medical Specialists

Waterloo, Iowa, United States

Location

Cancer Center of Kansas

Wichita, Kansas, United States

Location

University of Kentucky

Lexington, Kentucky, United States

Location

LSU Health Sciences Center - Shreveport

Shreveport, Louisiana, United States

Location

MaineGeneral Medical Center

Augusta, Maine, United States

Location

Missouri Cancer Associates

Columbia, Missouri, United States

Location

Kansas City Cancer Center

Kansas City, Missouri, United States

Location

UNM Cancer Center/New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States

Location

Interlakes Foundation, Inc

Rochester, New York, United States

Location

SUNY Upstate / Upstate Medical University

Syracuse, New York, United States

Location

Willamette Valley Cancer Center

Springfield, Oregon, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, United States

Location

Pennsylvania Oncology Hematology Associates, Inc.

Philadelphia, Pennsylvania, United States

Location

Charleston Hematology Oncology, PA

Charleston, South Carolina, United States

Location

Sarah Cannon Cancer Center

Nashville, Tennessee, United States

Location

Texas Oncology, P.A.

Fort Worth, Texas, United States

Location

Cancer Care Center of South Texas

San Antonio, Texas, United States

Location

Texas Oncology

Tyler, Texas, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, United States

Location

Cancer Outreach Asscociates, PC

Richlands, Virginia, United States

Location

Cancer Care Northwest-South

Spokane, Washington, United States

Location

Northwest Cancer Specialists, PC

Vancouver, Washington, United States

Location

West Virginia University School of Medicine

Morgantown, West Virginia, United States

Location

The Canberra Hospital

Garran, Australian Capital Territory, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

The Queen Elizabeth Hospital

Woodville, South Australia, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, Australia

Location

The Alfred Hospital

Melbourne, Victoria, Australia

Location

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Location

Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell

Interventions

Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Manager
• Organization: Teva Pharmaceuticals USA

clinicaltrialqueries@tevausa.com

1-866-384-5525

Study Officials

• Sponsor's Medical Expert

  Cephalon

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2010
• First Posted: February 23, 2010
• Study Start: February 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: April 24, 2014
• Results First Posted: April 4, 2014

Record last verified: 2014-04

Locations

CA (2); AU (5); US (36)