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Trial record 37 of 315 for:    BENDAMUSTINE

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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ClinicalTrials.gov Identifier: NCT01073163
Recruitment Status : Completed
First Posted : February 23, 2010
Results First Posted : April 4, 2014
Last Update Posted : April 24, 2014
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Cephalon )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Non-Hodgkin's Lymphoma
Mantle Cell Lymphoma
Interventions Drug: Bendamustine
Drug: Rituximab
Enrollment 54
Recruitment Details  
Pre-assignment Details Sixty-five patients were screened for this study; 8 did not meet eligibility criteria, and 3 were not enrolled for other reasons.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Period Title: Overall Study
Started 54
Enrolled But Not Treated 1
Treated With <6 Cycles 4
Treated With >=6 Cycles 49
Completed 51 [1]
Not Completed 3
Reason Not Completed
Adverse Event             1
Disease Progression             1
Early termination             1
[1]
Patients completed study
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Baseline Participants 54
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
AgeContinuous Number Analyzed 54 participants
62.9  (10.50)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants
Female
21
  38.9%
Male
33
  61.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants
Hispanic or Latino
2
   3.7%
Not Hispanic or Latino
50
  92.6%
Unknown or Not Reported
2
   3.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 54 participants
American Indian or Alaska Native 0
Asian 1
Native Hawaiian or Other Pacific Islander 0
Black or African American 0
White 49
Other 4
Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 54 participants
Score=0 29
Score=1 20
Score=2 5
Score=3 0
Score=4 0
[1]
Measure Description: 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.
1.Primary Outcome
Title Mean Change From Baseline in QT Interval as Corrected by the Fridericia Method (QTcF) at End of Infusion
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 53
Mean (Standard Deviation)
Unit of Measure: milliseconds (ms)
Baseline, n=53 410.4  (23.6)
End of Infusion, n=52 6.7  (10.3)
2.Secondary Outcome
Title Mean Change From Baseline in QTcF at 1 Hour Postinfusion
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 53
Mean (Standard Deviation)
Unit of Measure: ms
Baseline 410.4  (23.6)
1 Hour Postinfusion 4.1  (9.8)
3.Secondary Outcome
Title Number of Participants With QTcF New Outlier Events at End of Infusion and 1 Hour Postinfusion
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 53
Measure Type: Number
Unit of Measure: participants
QTcF New >500 ms at End of Infusion; n=52 0
QTcF New >500 ms 1 Hour Postinfusion; n=53 0
QTcF New >480 ms at End of Infusion; n=52 1
QTcF New >480 ms 1 Hour Postinfusion; n=53 0
QTcF New >60 ms at End of Infusion; n=52 0
QTcF New >60 ms 1 Hour Postinfusion; n=53 0
QTcF New 30-60 ms at End of Infusion; n=52 0
QTcF New 30-60 ms 1 Hour Postinfusion; n=53 0
4.Secondary Outcome
Title Number of Participants With New Onset ECG Waveform Morphological Changes
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 53
Measure Type: Number
Unit of Measure: participants
0
5.Secondary Outcome
Title Number of Participants With Treatment-Emergent Cardiac Disorders
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: enrolled participants who received 1 or more doses of study drug.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 53
Measure Type: Number
Unit of Measure: participants
ECG QT prolonged: Overall 3
ECG QT prolonged: Grade >/=3 2
Blood pressure decreased: Overall 1
Blood pressure decreased: Grade >/=3 1
Cardiac murmur: Overall 1
Cardiac murmur: Grade >/=3 0
ECG ST segment abnormal: Overall 1
ECG ST segment abnormal: Grade >/=3 0
Heart rate irregular: Overall 1
Heart rate irregular: Grade >/=3 0
Palpitations: Overall 2
Palpitations: Grade >/=3 0
Arteriosclerosis coronary artery: Overall 1
Arteriosclerosis coronary artery: Grade >/=3 0
Atrial fibrillation: Overall 1
Atrial fibrillation: Grade >/=3 0
Cardiac failure congestive: Overall 1
Cardiac failure congestive: Grade >/=3 0
Left ventricular dysfunction: Overall 1
Left ventricular dysfunction: Grade >/=3 1
Sinus tachycardia: Overall 1
Sinus tachycardia: Grade >/=3 0
Tachycardia: Overall 1
Tachycardia: Grade >/=3 0
6.Secondary Outcome
Title Change From Baseline in QTcF at Maximum Concentration (Cmax) of Bendamustine and Its Metabolites (M3 and M4)
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 51
Mean (95% Confidence Interval)
Unit of Measure: ms
Bendamustine
5.4097 [1] 
(NA to 7.5670)
Metabolite M3
5.9995 [1] 
(NA to 8.8415)
Metabolite M4
7.1390 [1] 
(NA to 10.0904)
[1]
One-sided confidence interval was calculated.
7.Secondary Outcome
Title Model-predicted Bayesian Bendamustine Clearance in the Presence of Rituximab
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 49
Median (Full Range)
Unit of Measure: L/h
32.9
(0.9 to 58.5)
8.Secondary Outcome
Title Rituximab Concentrations at 0.5 Hours, 24 Hours, and 7 Days Postinfusion
Hide Description [Not Specified]
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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 19
Median (Full Range)
Unit of Measure: mcg/mL
0.5 Hours Postinfusion; n=19
173.0
(74.5 to 299.0)
24 Hours Postinfusion; n=19
105.0
(4.62 to 176.0)
7 Days Postinfusion; n=17
30.5
(0.256 to 73.3)
9.Secondary Outcome
Title Percentage of Participants With Complete Response (CR)
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Non-Hodgkin Lymphoma Mantle Cell Lymphoma Total
Hide Arm/Group Description:
Participants with non-Hodgkin Lymphoma 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.
Participants with mantle cell lymphoma 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.
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.
Overall Number of Participants Analyzed 40 11 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
40
(24.9 to 56.7)
55
(23.4 to 83.3)
43
(29.3 to 57.8)
10.Secondary Outcome
Title Percentage of Participants With Overall Response
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Non-Hodgkin Lymphoma Mantle Cell Lymphoma Total
Hide Arm/Group Description:
Participants with non-Hodgkin Lymphoma 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.
Participants with mantle cell lymphoma 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.
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.
Overall Number of Participants Analyzed 40 11 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
93
(79.6 to 98.4)
100
(71.5 to 100.0)
94
(83.8 to 98.8)
11.Secondary Outcome
Title Overview of Adverse Events
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: enrolled participants who received 1 or more doses of study drug.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 53
Measure Type: Number
Unit of Measure: participants
Any adverse event 53
Severe adverse events (grade 3, 4, 5) 33
Treatment-related adverse events 52
Deaths 1
Other serious adverse events 14
Withdrawn from study due to adverse events 1
12.Secondary Outcome
Title Eastern Cooperative Oncology Group (ECOG) Performance Status at Endpoint
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: enrolled participants who received 1 or more doses of study drug.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 53
Measure Type: Number
Unit of Measure: participants
Improved 10
Stayed the same 35
Worsened 8
13.Secondary Outcome
Title Worst Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grades for Hematology Laboratory Tests Results Overall
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: enrolled participants who received 1 or more doses of study drug.
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 53
Measure Type: Number
Unit of Measure: participants
ANC, Grade 1: <LLN – 1.5*10^9/L 5
ANC, Grade 2: <1.5 – 1.0*10^9/L 12
ANC, Grade 3: <1.0 – 0.5*10^9/L 11
ANC, Grade 4: <0.5*10^9/L 12
ANC, Grade 1-4 40
Hemoglobin, Grade 1: <LLN – 100 g/L 36
Hemoglobin, Grade 2: <100 – 80 g/L 12
Hemoglobin, Grade 3: <80 – 65 g/L 1
Hemoglobin, Grade 4: <65 g/L 0
Hemoglobin, Grade 1-4 49
Lymphocytes ABS, Grade 1: <LLN - 0.8*10^9/L 0
Lymphocytes ABS, Grade 2: <0.8 – 0.5*10^9/L 2
Lymphocytes ABS, Grade 3: <0.5 – 0.2*10^9/L 13
Lymphocytes ABS, Grade 4: <0.2*10^9/L 22
Lymphocytes ABS, Grade 1-4 37
Platelets, Grade 1: <LLN – 75.0*10^9/L 19
Platelets, Grade 2: <75.0 – 50.0*10^9/L 9
Platelets, Grade 3: <50.0 – 25.0*10^9/L 3
Platelets, Grade 4: <25.0*10^9 /L 1
Platelets, Grade 1-4 32
WBC, Grade 1: <LLN – 3.0*10^9/L 9
WBC, Grade 2: <3.0 – 2.0*10^9/L 19
WBC, Grade 3: <2.0 – 1.0*10^9/L 15
WBC, Grade 4: <1.0*10^9/L 5
WBC, Grade 1-4 48
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.
Adverse Event Reporting Description Safety Analysis Set: enrolled participants who received 1 or more doses of study drug.
 
Arm/Group Title Bendamustine With Rituximab
Hide Arm/Group 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.
All-Cause Mortality
Bendamustine With Rituximab
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Bendamustine With Rituximab
Affected / at Risk (%) # Events
Total   14/53 (26.42%)    
Blood and lymphatic system disorders   
Febrile neutropenia * 1  1/53 (1.89%)  1
Neutropenia * 1  1/53 (1.89%)  1
Cardiac disorders   
Atrial fibrillation * 1  1/53 (1.89%)  1
Left ventricular dysfunction * 1  1/53 (1.89%)  1
Gastrointestinal disorders   
Appendix disorder * 1  1/53 (1.89%)  1
Ascites * 1  1/53 (1.89%)  1
Small intestinal obstruction * 1  1/53 (1.89%)  1
General disorders   
Asthenia * 1  1/53 (1.89%)  1
Chills * 1  1/53 (1.89%)  2
Pyrexia * 1  2/53 (3.77%)  3
Infections and infestations   
Bacteraemia * 1  1/53 (1.89%)  1
Cellulitis * 1  1/53 (1.89%)  1
Pneumonia * 1  1/53 (1.89%)  1
Urinary tract infection * 1  1/53 (1.89%)  1
Injury, poisoning and procedural complications   
Infusion related reaction * 1  3/53 (5.66%)  3
Metabolism and nutrition disorders   
Dehydration * 1  1/53 (1.89%)  1
Renal and urinary disorders   
Haematuria * 1  1/53 (1.89%)  1
Urinary retention * 1  1/53 (1.89%)  1
Respiratory, thoracic and mediastinal disorders   
Interstitial lung disease * 1  1/53 (1.89%)  1
Pleural effusion * 1  1/53 (1.89%)  1
Pneumonitis * 1  1/53 (1.89%)  1
Skin and subcutaneous tissue disorders   
Rash * 1  1/53 (1.89%)  1
Transient acantholytic dermatosis * 1  1/53 (1.89%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bendamustine With Rituximab
Affected / at Risk (%) # Events
Total   53/53 (100.00%)    
Blood and lymphatic system disorders   
Anaemia * 1  6/53 (11.32%)  18
Neutropenia * 1  19/53 (35.85%)  50
Thrombocytopenia * 1  11/53 (20.75%)  18
Gastrointestinal disorders   
Abdominal discomfort * 1  5/53 (9.43%)  5
Abdominal pain * 1  5/53 (9.43%)  9
Abdominal pain upper * 1  6/53 (11.32%)  6
Constipation * 1  22/53 (41.51%)  28
Diarrhoea * 1  16/53 (30.19%)  21
Dyspepsia * 1  4/53 (7.55%)  4
Gastrooesophageal reflux disease * 1  5/53 (9.43%)  5
Mouth ulceration * 1  3/53 (5.66%)  3
Nausea * 1  38/53 (71.70%)  56
Stomatitis * 1  7/53 (13.21%)  8
Vomiting * 1  16/53 (30.19%)  21
General disorders   
Asthenia * 1  3/53 (5.66%)  3
Chills * 1  7/53 (13.21%)  9
Fatigue * 1  27/53 (50.94%)  38
Feeling cold * 1  3/53 (5.66%)  3
Influenza like illness * 1  3/53 (5.66%)  3
Oedema peripheral * 1  4/53 (7.55%)  6
Pain * 1  6/53 (11.32%)  6
Pyrexia * 1  12/53 (22.64%)  20
Immune system disorders   
Drug hypersensitivity * 1  8/53 (15.09%)  10
Infections and infestations   
Nasopharyngitis * 1  4/53 (7.55%)  4
Oral herpes * 1  3/53 (5.66%)  3
Upper respiratory tract infection * 1  5/53 (9.43%)  5
Urinary tract infection * 1  5/53 (9.43%)  9
Injury, poisoning and procedural complications   
Contusion * 1  3/53 (5.66%)  3
Infusion related reaction * 1  19/53 (35.85%)  46
Investigations   
Electrocardiogram QT prolonged * 1  3/53 (5.66%)  4
Weight decreased * 1  6/53 (11.32%)  6
Metabolism and nutrition disorders   
Decreased appetite * 1  11/53 (20.75%)  12
Dehydration * 1  4/53 (7.55%)  5
Hypokalaemia * 1  5/53 (9.43%)  6
Hypomagnesaemia * 1  3/53 (5.66%)  5
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  3/53 (5.66%)  3
Back pain * 1  8/53 (15.09%)  9
Bone pain * 1  6/53 (11.32%)  7
Flank pain * 1  3/53 (5.66%)  3
Myalgia * 1  4/53 (7.55%)  4
Nervous system disorders   
Dizziness * 1  5/53 (9.43%)  6
Dysgeusia * 1  9/53 (16.98%)  10
Headache * 1  9/53 (16.98%)  10
Psychiatric disorders   
Anxiety * 1  5/53 (9.43%)  6
Depression * 1  4/53 (7.55%)  4
Insomnia * 1  12/53 (22.64%)  13
Renal and urinary disorders   
Nocturia * 1  3/53 (5.66%)  3
Pollakiuria * 1  4/53 (7.55%)  4
Respiratory, thoracic and mediastinal disorders   
Cough * 1  11/53 (20.75%)  12
Dysphonia * 1  4/53 (7.55%)  4
Dyspnoea * 1  7/53 (13.21%)  8
Dyspnoea exertional * 1  4/53 (7.55%)  4
Hiccups * 1  3/53 (5.66%)  4
Oropharyngeal pain * 1  3/53 (5.66%)  3
Pleural effusion * 1  3/53 (5.66%)  3
Productive cough * 1  3/53 (5.66%)  3
Wheezing * 1  3/53 (5.66%)  3
Skin and subcutaneous tissue disorders   
Alopecia * 1  4/53 (7.55%)  4
Night sweats * 1  3/53 (5.66%)  3
Pruritus * 1  3/53 (5.66%)  3
Rash * 1  7/53 (13.21%)  9
Vascular disorders   
Hot flush * 1  3/53 (5.66%)  3
Hypotension * 1  3/53 (5.66%)  3
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Manager
Organization: Teva Pharmaceuticals USA
Phone: 1-866-384-5525
EMail: clinicaltrialqueries@tevausa.com
Layout table for additonal information
Responsible Party: Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier: NCT01073163     History of Changes
Other Study ID Numbers: C18083/3070
First Submitted: February 19, 2010
First Posted: February 23, 2010
Results First Submitted: February 25, 2014
Results First Posted: April 4, 2014
Last Update Posted: April 24, 2014