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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bendamustine | Drug | Bendamustine at 90 mg/m^2 IV on Days 1 and 2 of a 28-day cycle. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): 1 hour postinfusion. |
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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:
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:
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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Sponsor's Medical Expert | Cephalon | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hematology Oncology Physicans Extenders Group | Tucson | Arizona | United States | |||
| University of Arkansas for Medical Sciences |
Sixty-five patients were screened for this study; 8 did not meet eligibility criteria, and 3 were not enrolled for other reasons.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Rituximab | Drug | Rituximab at 375 mg/m^2 IV on Day 1 of a 28-day cycle. |
|
|
| 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. | 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 | 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. | 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 | 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. | 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) | 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. | 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. |
| 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. | 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. |
| Rituximab Concentrations at 0.5 Hours, 24 Hours, and 7 Days Postinfusion | 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. |
| 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. | The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days. |
| 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. | The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days. |
| 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. | 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. |
| 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. | End of study. The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days. |
| 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 | 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. |
| 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 |
| Enrolled But Not Treated |
|
| Treated With <6 Cycles |
|
| Treated With >=6 Cycles |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| |||||||||||||||||||||||
| Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 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. | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | ECG Analysis Set: all enrolled participants in study who received at least 1 dose of study drug and with at least 1 available baseline and 1 on-treatment ECG; n=number of participants with measurement at given time point. | Posted | Mean | Standard Deviation | milliseconds (ms) | 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. |
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| Secondary | 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. | ECG Analysis Set: all enrolled participants in study who received at least 1 dose of study drug and with at least 1 available baseline and 1 on-treatment ECG. | Posted | Mean | Standard Deviation | ms | Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): 1 hour postinfusion. |
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| Secondary | 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. | ECG Analysis Set: all enrolled participants in study who received at least 1 dose of study drug and with at least 1 available baseline and 1 on-treatment ECG; n=number of participants with measurement at given time point. | Posted | Number | participants | 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. |
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| Secondary | 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. | ECG Analysis Set: all enrolled participants in study who received at least 1 dose of study drug and with at least 1 available baseline and 1 on-treatment ECG. | Posted | Number | participants | 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. |
|
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| Secondary | 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. | Safety Analysis Set: enrolled participants who received 1 or more doses of study drug. | Posted | Number | participants | 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. |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Pharmacokinetic-pharmacodynamic Analysis Set: all enrolled participants in study who received at least 1 dose of study drug and with at least 1 available baseline and 1 on-treatment ECG and at least 1 ECG with a time-matched plasma concentration pair. | Posted | Mean | 95% Confidence Interval | ms | 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. |
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| Secondary | 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. | Pharmacokinetic Analysis Set: all enrolled participants in study who received at least 1 dose of study drug and with at least 1 quantifiable bendamustine plasma concentration. | Posted | Median | Full Range | L/h | 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. |
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| Secondary | Rituximab Concentrations at 0.5 Hours, 24 Hours, and 7 Days Postinfusion | Pharmacokinetic Analysis Set: all enrolled participants in study who received at least 1 dose of study drug and with at least 1 quantifiable serum concentration of rituximab. | Posted | Median | Full Range | mcg/mL | 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. |
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| Secondary | 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. | Full Analysis Set: all enrolled participants who received at least 1 dose of both bendamustine and rituximab and who had both a baseline and at least 1 postbaseline tumor response evaluation. | Posted | Number | 95% Confidence Interval | percentage of participants | The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days. |
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Full Analysis Set: all enrolled participants who received at least 1 dose of both bendamustine and rituximab and who had both a baseline and at least 1 postbaseline tumor response evaluation. | Posted | Number | 95% Confidence Interval | percentage of participants | The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days. |
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety Analysis Set: enrolled participants who received 1 or more doses of study drug. | Posted | Number | participants | 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. |
| |||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety Analysis Set: enrolled participants who received 1 or more doses of study drug. | Posted | Number | participants | End of study. The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days. |
|
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| Secondary | 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 | Safety Analysis Set: enrolled participants who received 1 or more doses of study drug. | Posted | Number | participants | 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. |
|
|
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.
Safety Analysis Set: enrolled participants who received 1 or more doses of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 14 | 53 | 53 | 53 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Appendix disorder | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Transient acantholytic dermatosis | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Feeling cold | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 15.0 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 15.0 | Non-systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Nocturia | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 15.0 | Non-systematic Assessment |
|
Investigator/Institution must submit proposed publication to Sponsor for review within a prespecified number of days before submission for publication. If Sponsor's review shows that potentially patentable subject matter would be disclosed, publication/public disclosure shall be delayed to enable Sponsor, or Sponsor's designees, to file necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Manager | Teva Pharmaceuticals USA | 1-866-384-5525 | clinicaltrialqueries@tevausa.com |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D020522 | Lymphoma, Mantle-Cell |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069461 | Bendamustine Hydrochloride |
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| Other |
|
| Title | Measurements |
|---|
|
| Score=2 |
|
| Score=3 |
|
| Score=4 |
|
|
|
|
|
|
|
|
|
|
All participants 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. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Participants |
|
|
|