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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)

Primary Purpose

Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Bendamustine
Rituximab
Sponsored by
Cephalon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key 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

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 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

Sites / Locations

  • Hematology Oncology Physicans Extenders Group
  • University of Arkansas for Medical Sciences
  • St. Jude Heritage Medical Group
  • Comprehensive Cancer Center
  • University of Colorado Cancer Center
  • Rocky Mountain Cancer Center
  • The Hospital of Central Connecticut
  • Cancer Center of Central Connecticut
  • Memorial Cancer Institute
  • Cancer Centers of Florida
  • MD Anderson Cancer Cnt Orlando
  • John B Amos Cancer Center
  • St Francis Cancer Research Foundation
  • Cedar Valley Medical Specialists
  • Cancer Center of Kansas
  • University of Kentucky
  • LSU Health Sciences Center - Shreveport
  • MaineGeneral Medical Center
  • Missouri Cancer Associates
  • Kansas City Cancer Center
  • UNM Cancer Center/New Mexico Cancer Care Alliance
  • Interlakes Foundation, Inc
  • SUNY Upstate / Upstate Medical University
  • Willamette Valley Cancer Center
  • Geisinger Medical Center
  • Pennsylvania Oncology Hematology Associates, Inc.
  • Charleston Hematology Oncology, PA
  • Sarah Cannon Cancer Center
  • Texas Oncology, P.A.
  • Cancer Care Center of South Texas
  • Texas Oncology
  • Virginia Oncology Associates
  • Cancer Outreach Asscociates, PC
  • Cancer Care Northwest-South
  • Northwest Cancer Specialists, PC
  • West Virginia University School of Medicine
  • The Canberra Hospital
  • Royal Adelaide Hospital
  • The Queen Elizabeth Hospital
  • Royal Hobart Hospital
  • The Alfred Hospital
  • Queen Elizabeth II Health Sciences Centre
  • Ottawa Hospital - General Campus

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bendamustine with Rituximab

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Mean Change From Baseline in QTcF at 1 Hour Postinfusion
On Day 2 of Cycle 1, three 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 1 hour postinfusion.
Number of Participants With QTcF New Outlier Events at End of Infusion and 1 Hour Postinfusion
Participants were considered to have an outlier ECG value based on the most extreme value across each of the time points. "New" means not present at baseline and becomes present on at least 1 on-treatment ECG time point. A participant had a new outlier event (500) if the maximum QTcF was >500 ms while their baseline was <=500 ms, or had an outlier event (480) if the maximum QTcF was >480 ms while their baseline was <= 480 ms. QTcF in the 30-60 ms or >60 ms categories were also considered outliers.
Number of Participants With New Onset ECG Waveform Morphological Changes
The core ECG laboratory cardiologist assessed all leads in the ECGs and defined morphological changes. Changes from baseline (looking at each of the 3 ECGs at Day 2 Cycle 1 individually and the ECGs at all on-treatment time points individually) were noted for the following events: atrial fibrillation or flutter; second degree heart block; third degree heart block; complete right bundle branch block; complete left bundle branch block; ST segment depression; T wave abnormalities (negative T waves only); myocardial infarction pattern; any new abnormal U waves.
Number of Participants With Treatment-Emergent Cardiac Disorders
Number of participants with cardiac disorders overall, with severity from grades 1 (mild) to grade 4 (severe), according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5= death). Participants may have reported more than 1 event.
Change From Baseline in QTcF at Maximum Concentration (Cmax) of Bendamustine and Its Metabolites (M3 and M4)
Results from a pharmacokinetic-pharmacodynamic model to show the relationship of the overall predicted change from Baseline in QTcF at the average Cmax of bendamustine and its metabolites M3 and M4.
Model-predicted Bayesian Bendamustine Clearance in the Presence of Rituximab
Boxplots of model-predicted Bayesian bendamustine clearance (CL) values in the presence of rituximab were generated based on the administered bendamustine doses, rate of infusion, and sample times.
Rituximab Concentrations at 0.5 Hours, 24 Hours, and 7 Days Postinfusion
Percentage of Participants With Complete Response (CR)
Complete response, as defined by the International Working Group (IWG) Revised Response Criteria For Malignant Lymphoma. Results are presented for participants with non-Hodgkin lymphoma and mantle cell lymphoma as well as all participants.
Percentage of Participants With Overall Response
Overall Response was comprised of those participants who had Complete Response (CR) plus those who had Partial Response (PR), as defined by the International Working Group (IWG) Revised Response Criteria For Malignant Lymphoma. Results are presented for participants with non-Hodgkin lymphoma and mantle cell lymphoma as well as all participants.
Overview of Adverse Events
Adverse event (AE)=any untoward medical occurrence in a patient administered study drug that develops or worsens in severity during the conduct of a clinical study of a pharmaceutical product and does not necessarily have a causal relationship to the study drug. Treatment-related AEs=those that began or worsened after treatment with study drug. AE severity was graded according to the National Cancer Institute's Common Terminology Criteria for AEs (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5= death). Relationship of an AE to study drug was categorized as definite, probable, possible, unlikely, or not related. Serious AE (SAE)=one that occurred at any dose that resulted in any of the following outcomes or actions: death; a life-threatening adverse event; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability/incapacity; a congenital anomaly/birth defect; or an otherwise important medical event.
Eastern Cooperative Oncology Group (ECOG) Performance Status at Endpoint
The investigator assessed each patient's ECOG performance status according to the ECOG scale at screening, on Day 1 of each treatment cycle, and at the end-of-treatment visit. Scale scores were: 0=fully active, able to carry on all pre-disease performance without restriction; 1=restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2=ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5=dead. Any change in score to a higher value signifies worsening, and any change to a lower value signifies improvement.
Worst Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grades for Hematology Laboratory Tests Results Overall
Grade 1=Mild, 2=Moderate, 3=Severe/medically significant, 4=Life-threatening. Overall is defined as the worst postbaseline grade value for each patient and laboratory test across all cycles. Only postbaseline grades are summarized. If absolute neutrophil count (ANC) and neutrophils absolute (ABS) were both measured, the worse grade value from the two was summarized. Otherwise the worst ANC grade value or the worst neutrophils ABS grade value was summarized. WBC=white blood cell; LLN=lower limit of normal

Full Information

First Posted
February 19, 2010
Last Updated
April 7, 2014
Sponsor
Cephalon
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1. Study Identification

Unique Protocol Identification Number
NCT01073163
Brief Title
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)
Official Title
A 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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
February 2010 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cephalon

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bendamustine with Rituximab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treakisym, Ribomustin, Levact, Treanda, SDX-105
Intervention Description
Bendamustine at 90 mg/m^2 IV on Days 1 and 2 of a 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan, MabThera, IDEC-C2B8
Intervention Description
Rituximab at 375 mg/m^2 IV on Day 1 of a 28-day cycle.
Primary Outcome Measure Information:
Title
Mean Change From Baseline in QT Interval as Corrected by the Fridericia Method (QTcF) at End of Infusion
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Mean Change From Baseline in QTcF at 1 Hour Postinfusion
Description
On Day 2 of Cycle 1, three 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 1 hour postinfusion.
Time Frame
Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): 1 hour postinfusion.
Title
Number of Participants With QTcF New Outlier Events at End of Infusion and 1 Hour Postinfusion
Description
Participants were considered to have an outlier ECG value based on the most extreme value across each of the time points. "New" means not present at baseline and becomes present on at least 1 on-treatment ECG time point. A participant had a new outlier event (500) if the maximum QTcF was >500 ms while their baseline was <=500 ms, or had an outlier event (480) if the maximum QTcF was >480 ms while their baseline was <= 480 ms. QTcF in the 30-60 ms or >60 ms categories were also considered outliers.
Time Frame
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.
Title
Number of Participants With New Onset ECG Waveform Morphological Changes
Description
The core ECG laboratory cardiologist assessed all leads in the ECGs and defined morphological changes. Changes from baseline (looking at each of the 3 ECGs at Day 2 Cycle 1 individually and the ECGs at all on-treatment time points individually) were noted for the following events: atrial fibrillation or flutter; second degree heart block; third degree heart block; complete right bundle branch block; complete left bundle branch block; ST segment depression; T wave abnormalities (negative T waves only); myocardial infarction pattern; any new abnormal U waves.
Time Frame
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.
Title
Number of Participants With Treatment-Emergent Cardiac Disorders
Description
Number of participants with cardiac disorders overall, with severity from grades 1 (mild) to grade 4 (severe), according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5= death). Participants may have reported more than 1 event.
Time Frame
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.
Title
Change From Baseline in QTcF at Maximum Concentration (Cmax) of Bendamustine and Its Metabolites (M3 and M4)
Description
Results from a pharmacokinetic-pharmacodynamic model to show the relationship of the overall predicted change from Baseline in QTcF at the average Cmax of bendamustine and its metabolites M3 and M4.
Time Frame
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.
Title
Model-predicted Bayesian Bendamustine Clearance in the Presence of Rituximab
Description
Boxplots of model-predicted Bayesian bendamustine clearance (CL) values in the presence of rituximab were generated based on the administered bendamustine doses, rate of infusion, and sample times.
Time Frame
Day 1 of Cycle 1: prior to start of bendamustine infusion, immediately postinfusion, 15 minutes and 30 minutes postinfusion. Day 2 of Cycle 1: 15 minutes prior to start of bendamustine infusion, 15 minutes, 30 minutes, 1, 3, and 5 hours postinfusion.
Title
Rituximab Concentrations at 0.5 Hours, 24 Hours, and 7 Days Postinfusion
Time Frame
Day 1 of Cycle 1: prior to start of rituximab infusion, immediately postinfusion. Day 2 of Cycle 1: 15 minutes prior to the start of the bendamustine infusion. Day 7 and Day 14: anytime. Day 1 of Cycle 2: prior to start of rituximab infusion.
Title
Percentage of Participants With Complete Response (CR)
Description
Complete response, as defined by the International Working Group (IWG) Revised Response Criteria For Malignant Lymphoma. Results are presented for participants with non-Hodgkin lymphoma and mantle cell lymphoma as well as all participants.
Time Frame
The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days.
Title
Percentage of Participants With Overall Response
Description
Overall Response was comprised of those participants who had Complete Response (CR) plus those who had Partial Response (PR), as defined by the International Working Group (IWG) Revised Response Criteria For Malignant Lymphoma. Results are presented for participants with non-Hodgkin lymphoma and mantle cell lymphoma as well as all participants.
Time Frame
The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days.
Title
Overview of Adverse Events
Description
Adverse event (AE)=any untoward medical occurrence in a patient administered study drug that develops or worsens in severity during the conduct of a clinical study of a pharmaceutical product and does not necessarily have a causal relationship to the study drug. Treatment-related AEs=those that began or worsened after treatment with study drug. AE severity was graded according to the National Cancer Institute's Common Terminology Criteria for AEs (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5= death). Relationship of an AE to study drug was categorized as definite, probable, possible, unlikely, or not related. Serious AE (SAE)=one that occurred at any dose that resulted in any of the following outcomes or actions: death; a life-threatening adverse event; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability/incapacity; a congenital anomaly/birth defect; or an otherwise important medical event.
Time Frame
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.
Title
Eastern Cooperative Oncology Group (ECOG) Performance Status at Endpoint
Description
The investigator assessed each patient's ECOG performance status according to the ECOG scale at screening, on Day 1 of each treatment cycle, and at the end-of-treatment visit. Scale scores were: 0=fully active, able to carry on all pre-disease performance without restriction; 1=restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2=ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5=dead. Any change in score to a higher value signifies worsening, and any change to a lower value signifies improvement.
Time Frame
End of study. The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days.
Title
Worst Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grades for Hematology Laboratory Tests Results Overall
Description
Grade 1=Mild, 2=Moderate, 3=Severe/medically significant, 4=Life-threatening. Overall is defined as the worst postbaseline grade value for each patient and laboratory test across all cycles. Only postbaseline grades are summarized. If absolute neutrophil count (ANC) and neutrophils absolute (ABS) were both measured, the worse grade value from the two was summarized. Otherwise the worst ANC grade value or the worst neutrophils ABS grade value was summarized. WBC=white blood cell; LLN=lower limit of normal
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key 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: 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-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 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sponsor's Medical Expert
Organizational Affiliation
Cephalon
Official's Role
Study Director
Facility Information:
Facility Name
Hematology Oncology Physicans Extenders Group
City
Tucson
State/Province
Arizona
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
St. Jude Heritage Medical Group
City
Fullerton
State/Province
California
Country
United States
Facility Name
Comprehensive Cancer Center
City
Palm Springs
State/Province
California
Country
United States
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
Country
United States
Facility Name
Rocky Mountain Cancer Center
City
Denver
State/Province
Colorado
Country
United States
Facility Name
The Hospital of Central Connecticut
City
New Britain
State/Province
Connecticut
Country
United States
Facility Name
Cancer Center of Central Connecticut
City
Southington
State/Province
Connecticut
Country
United States
Facility Name
Memorial Cancer Institute
City
Hollywood
State/Province
Florida
Country
United States
Facility Name
Cancer Centers of Florida
City
Orlando
State/Province
Florida
Country
United States
Facility Name
MD Anderson Cancer Cnt Orlando
City
Orlando
State/Province
Florida
Country
United States
Facility Name
John B Amos Cancer Center
City
Columbus
State/Province
Georgia
Country
United States
Facility Name
St Francis Cancer Research Foundation
City
Beech Grove
State/Province
Indiana
Country
United States
Facility Name
Cedar Valley Medical Specialists
City
Waterloo
State/Province
Iowa
Country
United States
Facility Name
Cancer Center of Kansas
City
Wichita
State/Province
Kansas
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
Country
United States
Facility Name
LSU Health Sciences Center - Shreveport
City
Shreveport
State/Province
Louisiana
Country
United States
Facility Name
MaineGeneral Medical Center
City
Augusta
State/Province
Maine
Country
United States
Facility Name
Missouri Cancer Associates
City
Columbia
State/Province
Missouri
Country
United States
Facility Name
Kansas City Cancer Center
City
Kansas City
State/Province
Missouri
Country
United States
Facility Name
UNM Cancer Center/New Mexico Cancer Care Alliance
City
Albuquerque
State/Province
New Mexico
Country
United States
Facility Name
Interlakes Foundation, Inc
City
Rochester
State/Province
New York
Country
United States
Facility Name
SUNY Upstate / Upstate Medical University
City
Syracuse
State/Province
New York
Country
United States
Facility Name
Willamette Valley Cancer Center
City
Springfield
State/Province
Oregon
Country
United States
Facility Name
Geisinger Medical Center
City
Danville
State/Province
Pennsylvania
Country
United States
Facility Name
Pennsylvania Oncology Hematology Associates, Inc.
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Charleston Hematology Oncology, PA
City
Charleston
State/Province
South Carolina
Country
United States
Facility Name
Sarah Cannon Cancer Center
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Texas Oncology, P.A.
City
Fort Worth
State/Province
Texas
Country
United States
Facility Name
Cancer Care Center of South Texas
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
Texas Oncology
City
Tyler
State/Province
Texas
Country
United States
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
Country
United States
Facility Name
Cancer Outreach Asscociates, PC
City
Richlands
State/Province
Virginia
Country
United States
Facility Name
Cancer Care Northwest-South
City
Spokane
State/Province
Washington
Country
United States
Facility Name
Northwest Cancer Specialists, PC
City
Vancouver
State/Province
Washington
Country
United States
Facility Name
West Virginia University School of Medicine
City
Morgantown
State/Province
West Virginia
Country
United States
Facility Name
The Canberra Hospital
City
Garran
State/Province
Australian Capital Territory
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
Country
Australia
Facility Name
The Queen Elizabeth Hospital
City
Woodville
State/Province
South Australia
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
Country
Australia
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
Country
Australia
Facility Name
Queen Elizabeth II Health Sciences Centre
City
Halifax
State/Province
Nova Scotia
Country
Canada
Facility Name
Ottawa Hospital - General Campus
City
Ottawa
State/Province
Ontario
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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)

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