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Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia

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ClinicalTrials.gov Identifier: NCT01088984
Recruitment Status : Completed
First Posted : March 18, 2010
Results First Posted : October 1, 2014
Last Update Posted : May 23, 2016
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia
Intervention Drug: Bendamustine
Enrollment 43
Recruitment Details Of the 46 patients screened, 43 patients at 24 centers from the United States, Australia, South Korea, Israel, Mexico, and Brazil met entry criteria and were considered eligible for enrollment. Of the 3 patients who were not enrolled, 2 patients died prior to study enrollment, and 1 patient was ineligible because inclusion criteria were not met.
Pre-assignment Details  
Arm/Group Title Bendamustine 90 mg/m^2 Bendamustine 120 mg/m^2
Hide Arm/Group Description Bendamustine 90 mg/m^2 administered as an intravenous (IV) infusion over 60 minutes on Days 1 and 2 of a 21-day Induction cycle, with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle. Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (maximum of 12 total cycles), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Period Title: Phase 1
Started 5 6
Completed 0 [1] 0 [1]
Not Completed 5 6
Reason Not Completed
Death             2             1
Disease Progression             2             4
Not Specified             1             1
[1]
completed follow-up up to 12 month from last dose of study drug
Period Title: Phase 2
Started 0 32
Completed 0 [1] 0 [1]
Not Completed 0 32
Reason Not Completed
Death             0             5
Withdrawal by Subject             0             1
DIsease Progression             0             25
Not Specified             0             1
[1]
completed follow-up up to 12 month from last dose of study drug
Arm/Group Title Phase 1: Bendamustine 90 or 120 mg/m^2 Phase 2: Bendamustine 120 mg/m^2 Total
Hide Arm/Group Description Bendamustine 90 or 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of a 21-day Induction Cycle, with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle. Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (Cycles 2 through 12), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle. Total of all reporting groups
Overall Number of Baseline Participants 11 32 43
Hide Baseline Analysis Population Description
Includes 5 participants treated with bendamustine at 90 mg/m2 in Phase 1, and 6 participants treated with bendamustine at 120 mg/m2 in Phase 1, and 32 participants treated with the recommended phase II dose (RP2D) of bendamustine (120 mg/m2) in Phase 2.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 11 participants 32 participants 43 participants
8.7  (4.31) 9.3  (4.93) 9.2  (4.74)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 11 participants 32 participants 43 participants
1 to 6 years 4 10 14
7 to 11 years 3 10 13
12 to 20 years 4 12 16
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 32 participants 43 participants
Female
1
   9.1%
12
  37.5%
13
  30.2%
Male
10
  90.9%
20
  62.5%
30
  69.8%
1.Primary Outcome
Title Recommended Phase II Dose (RP2D) of Bendamustine
Hide Description RP2D was determined by a traditional 3+3 dose escalation design, with the following restrictions: only doses of 60, 90, 120, and 150 mg/m^2 were explored, and escalation to 150 mg/m^2 would only occur if the 120 mg/m^2 dose was deemed safe and pharmacokinetic data indicate subtherapeutic exposure as compared with adults. The first cohort was administered bendamustine at the 90 mg/m^2 dose; de-escalation to the 60 mg/m^2 dose would only occur if the starting dose led to dose-limiting toxicity (DLT) in 2 or more participants. A DLT was defined as any study drug-related nonhematologic adverse event (AE) that was grade 4 for toxicity by National Cancer Institute's Common Toxicity Criteria for AEs, version 4. In addition, grade 3 or above allergic reaction or skin rash were considered DLTs. Hematologic AEs were not considered DLTs. The dose level at which at least 2 of 3 or 2 of 6 participants had a DLT was considered as exceeding the RP2D. The RP2D was the dose 1 step below that level.
Time Frame Induction Cycle (21- to 35-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled in Phase 1 of the study.
Arm/Group Title Phase 1: Bendamustine 90 or 120 mg/m^2
Hide Arm/Group Description:
Bendamustine 90 or 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of a 21-day Induction Cycle, with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: mg/m^2
120
2.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description ORR was calculated as follows: number of participants in the primary analysis set achieving a best overall response of complete remission without platelet recovery (CRp) or complete remission (CR), divided by the number of participants in the primary analysis set. The most positive response for each patient during the study was counted. The 95% CI was calculated using binomial parameter exact method. Response was determined by the investigator, and evaluated per Jeha et al, 2006: A CR required no evidence of circulating blasts or extramedullary disease, an M1 marrow (≤ 5% bone marrow blasts), and recovery of peripheral counts (platelets ≥ 100 × 10^9/L and absolute neutrophil count ≥ 1.0 × 10^9/L). A CR without platelet recovery (CRp) required all of the criteria for a CR with the exception of platelet recovery.
Time Frame Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis set for efficacy included all participants treated at the RP2D in Phase 2.
Arm/Group Title Phase 2: Bendamustine 120 mg/m^2
Hide Arm/Group Description:
Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (Cycles 2 through 12), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Overall Number of Participants Analyzed 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 [1] 
(0.00 to NA)
[1]
1-sided 95% confidence interval
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2: Bendamustine 120 mg/m^2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments 1-sided p-value is calculated against the null hypothesis of a response rate of 5%.
Method binomial parameter exact method
Comments [Not Specified]
3.Secondary Outcome
Title Best Overall Tumor Response Rate
Hide Description Biological activity of bendamustine was defined as achieving a best response of partial response (PR), CRp, or CR. Rate was calculated as follows: number of participants in the primary analysis set achieving a best overall response of PR, CRp, or CR, divided by the number of participants in the primary analysis set. The most positive response for each patient during the study was counted. The 95% CI was calculated using binomial parameter exact method. Response was determined by the investigator, and evaluated per Jeha et al, 2006: A PR had to meet the following criteria: complete disappearance of circulating blasts and an M2 marrow (≥ 5% and ≤ 25% bone marrow blasts) and appearance of normal progenitor cells or an M1 marrow that did not qualify for CR or CRp. See Outcome Measure 2 for full definitions for CRp and CR.
Time Frame At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis set for efficacy included all participants treated at the RP2D in Phase 2.
Arm/Group Title Phase 2: Bendamustine 120 mg/m^2
Hide Arm/Group Description:
Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (Cycles 2 through 12), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Overall Number of Participants Analyzed 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
6
(0.77 to 20.81)
4.Secondary Outcome
Title Best Overall Tumor Response Rate, by Phase
Hide Description Biological activity of bendamustine was defined as achieving a best response of partial response (PR), CRp, or CR. Rate was calculated as follows: number of participants in the primary analysis set achieving a best overall response of PR, CRp, or CR, divided by the number of participants in the primary analysis set. The most positive response for each patient during the study was counted. The 95% CI was calculated using binomial parameter exact method. Response was determined by the investigator, and evaluated per Jeha et al, 2006: A PR had to meet the following criteria: complete disappearance of circulating blasts and an M2 marrow (≥ 5% and ≤ 25% bone marrow blasts) and appearance of normal progenitor cells or an M1 marrow that did not qualify for CR or CRp. See Outcome Measure 2 for full definitions for CRp and CR.
Time Frame At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants treated at any dose of bendamustine.
Arm/Group Title Phase 1: Bendamustine 90 or 120 mg/m^2 Phase 2: Bendamustine 120 mg/m^2 Total
Hide Arm/Group Description:
Bendamustine 90 or 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of a 21-day Induction Cycle, with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (Cycles 2 through 12), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Bendamustine 90 or 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (maximum of 12 total cycles), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Overall Number of Participants Analyzed 11 32 43
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18
(2.28 to 51.78)
6
(0.77 to 20.81)
9
(2.59 to 22.14)
5.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR was determined for the participants with CR or CRp in the primary analysis set, defined as the time from first achieving remission to the time when progression was diagnosed, the participant died, or the participant started receiving new antineoplastic therapy. Data from participants who do not progress were censored at the last valid assessments. Median DOR and its 95% confidence interval was determined based on the Kaplan-Meier method. Data from participants who received a transplant were censored at the time of the transplant.
Time Frame At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
No duration of remission (defined as CR or CRp) analysis was performed for participants in the primary analysis since none achieved remission.
Arm/Group Title Phase 2: Bendamustine 120 mg/m^2
Hide Arm/Group Description:
Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (Cycles 2 through 12), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Maximum Observed Plasma Drug Concentration (Cmax) for Bendamustine and Its Metabolites (M3 and M4)
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic analysis set included all participants who were in the safety analysis set (ie, those treated at any dose of bendamustine) who had valid pharmacokinetic data; n=number of participants with valid data for this assessment.
Arm/Group Title Bendamustine 90 mg/m^2 Bendamustine 120 mg/m^2
Hide Arm/Group Description:
Bendamustine 90 mg/m^2 administered as an intravenous (IV) infusion over 60 minutes on Days 1 and 2 of a 21-day Induction cycle, with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (maximum of 12 total cycles), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Overall Number of Participants Analyzed 5 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Bendamustine; n=5, 37
5093.24
(60.39%)
6401.80
(52.90%)
Metabolite M3; n=5, 36
311.70
(92.98%)
403.52
(69.91%)
Metabolite M4; n=5, 37
37.53
(82.97%)
48.27
(53.94%)
7.Secondary Outcome
Title Time to Maximum Plasma Drug Concentration (Tmax) for Bendamustine and Its Metabolites (M3 and M4)
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic analysis set included all participants who were in the safety analysis set (ie, those treated at any dose of bendamustine) who had valid pharmacokinetic data; n=number of participants with valid data for this assessment.
Arm/Group Title Bendamustine 90 mg/m^2 Bendamustine 120 mg/m^2
Hide Arm/Group Description:
Bendamustine 90 mg/m^2 administered as an intravenous (IV) infusion over 60 minutes on Days 1 and 2 of a 21-day Induction cycle, with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (maximum of 12 total cycles), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Overall Number of Participants Analyzed 5 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
Bendamustine; n=5, 37
1.14
(10.00%)
1.07
(9.49%)
Metabolite M3; n=5, 36
1.14
(10.00%)
1.07
(9.53%)
Metabolite M4; n=5, 37
1.14
(10.00%)
1.07
(9.49%)
8.Secondary Outcome
Title Area Under the Plasma Drug Concentration by Time Curve From Time 0 Until the Last Measurable Plasma Concentration (AUC0-t) for Bendamustine and Its Metabolites (M3 and M4)
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic analysis set included all participants who were in the safety analysis set (ie, those treated at any dose of bendamustine) who had valid pharmacokinetic data; n=number of participants with valid data for this assessment.
Arm/Group Title Bendamustine 90 mg/m^2 Bendamustine 120 mg/m^2
Hide Arm/Group Description:
Bendamustine 90 mg/m^2 administered as an intravenous (IV) infusion over 60 minutes on Days 1 and 2 of a 21-day Induction cycle, with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (maximum of 12 total cycles), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Overall Number of Participants Analyzed 5 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Bendamustine; n=5, 37
11174.86
(51.73%)
11046.32
(58.58%)
Metabolite M3; n=5, 36
697.09
(88.37%)
701.19
(67.38%)
Metabolite M4; n=5, 37
43.80
(109.72%)
72.78
(57.11%)
9.Secondary Outcome
Title Area Under the Plasma Drug Concentration by Time Curve From Time 0 Until 24 Hours After Study Drug Administration (AUC0-24) for Bendamustine and Its Metabolites (M3 and M4)
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic analysis set included all participants who were in the safety analysis set (ie, those treated at any dose of bendamustine) who had valid pharmacokinetic data; n=number of participants with valid data for this assessment.
Arm/Group Title Bendamustine 90 mg/m^2 Bendamustine 120 mg/m^2
Hide Arm/Group Description:
Bendamustine 90 mg/m^2 administered as an intravenous (IV) infusion over 60 minutes on Days 1 and 2 of a 21-day Induction cycle, with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (maximum of 12 total cycles), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Overall Number of Participants Analyzed 5 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Bendamustine; n=1, 13
14998.00 [1] 
(NA%)
12929.22
(50.46%)
Metabolite M3; n=0, 2
NA [2] 
(NA%)
1336.89
(1.80%)
Metabolite M4; n=0, 0
NA [2] 
(NA%)
NA [2] 
(NA%)
[1]
only 1 participant assessed
[2]
no participants assessed
Time Frame Screening (Day -14 to Day-1) through end of treatment (up to 12 35-day cycles), plus 30 days.
Adverse Event Reporting Description Participants were given both dosages for varying lengths and the adverse events were not reported according to which timepoint neither at which dosage events occurred.
 
Arm/Group Title Bendamustine
Hide Arm/Group Description Bendamustine 90 or 120 mg/m^2 administered as an intravenous (IV) infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (maximum of 12 total cycles), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
All-Cause Mortality
Bendamustine
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Bendamustine
Affected / at Risk (%) # Events
Total   33/43 (76.74%)    
Blood and lymphatic system disorders   
Febrile neutropenia  1  12/43 (27.91%)  13
Leukocytosis  1  1/43 (2.33%)  1
Neutropenia  1  2/43 (4.65%)  2
Pancytopenia  1  2/43 (4.65%)  2
Thrombocytopenia  1  2/43 (4.65%)  2
Cardiac disorders   
Cardiopulmonary failure  1  1/43 (2.33%)  1
Gastrointestinal disorders   
Proctitis  1  1/43 (2.33%)  1
Vomiting  1  1/43 (2.33%)  1
General disorders   
Chest pain  1  1/43 (2.33%)  1
Multi-organ failure  1  1/43 (2.33%)  2
Pyrexia  1  4/43 (9.30%)  7
Hepatobiliary disorders   
Portal vein thrombosis  1  1/43 (2.33%)  1
Infections and infestations   
Aspergillosis  1  2/43 (4.65%)  2
Bacteraemia  1  1/43 (2.33%)  1
Beta haemolytic streptococcal infection  1  1/43 (2.33%)  1
Capnocytophagia infection  1  1/43 (2.33%)  1
Cellulitis  1  1/43 (2.33%)  2
Febrile infection  1  1/43 (2.33%)  1
Fungal sepsis  1  1/43 (2.33%)  1
Herpes zoster  1  2/43 (4.65%)  3
Pharyngitis  1  1/43 (2.33%)  1
Pneumonia  1  1/43 (2.33%)  1
Septic shock  1  1/43 (2.33%)  1
Staphylococcal infection  1  1/43 (2.33%)  2
Investigations   
Blood creatinine increased  1  1/43 (2.33%)  1
Electrocardiogram QT prolonged  1  1/43 (2.33%)  1
Metabolism and nutrition disorders   
Hypercalcaemia  1  1/43 (2.33%)  1
Hyperglycaemia  1  1/43 (2.33%)  1
Hyperkalaemia  1  1/43 (2.33%)  1
Tumour lysis syndrome  1  1/43 (2.33%)  1
Musculoskeletal and connective tissue disorders   
Back pain  1  1/43 (2.33%)  3
Pain in extremity  1  1/43 (2.33%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Acute lymphocytic leukaemia  1  4/43 (9.30%)  4
Acute myeloid leukaemia  1  3/43 (6.98%)  3
B precursor type acute leukaemia  1  1/43 (2.33%)  1
Leukaemia  1  2/43 (4.65%)  4
Myeloid leukaemia  1  1/43 (2.33%)  1
T-cell type acute leukaemia  1  1/43 (2.33%)  1
Nervous system disorders   
Depressed level of consciousness  1  2/43 (4.65%)  2
Headache  1  1/43 (2.33%)  1
Psychiatric disorders   
Confusional state  1  1/43 (2.33%)  1
Renal and urinary disorders   
Renal failure  1  1/43 (2.33%)  1
Renal impairment  1  2/43 (4.65%)  2
Respiratory, thoracic and mediastinal disorders   
Hypoxia  1  2/43 (4.65%)  2
Respiratory distress  1  1/43 (2.33%)  1
Respiratory failure  1  1/43 (2.33%)  1
Vascular disorders   
Hypotension  1  1/43 (2.33%)  1
Peripheral artery aneurysm  1  1/43 (2.33%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bendamustine
Affected / at Risk (%) # Events
Total   43/43 (100.00%)    
Blood and lymphatic system disorders   
Anaemia  1  28/43 (65.12%)  92
Febrile neutropenia  1  15/43 (34.88%)  19
Lymphopenia  1  3/43 (6.98%)  10
Neutropenia  1  5/43 (11.63%)  8
Pancytopenia  1  4/43 (9.30%)  5
Thrombocytopenia  1  14/43 (32.56%)  74
Gastrointestinal disorders   
Abdominal pain  1  9/43 (20.93%)  13
Constipation  1  7/43 (16.28%)  8
Diarrhoea  1  14/43 (32.56%)  28
Gingival bleeding  1  3/43 (6.98%)  3
Nausea  1  20/43 (46.51%)  26
Vomiting  1  15/43 (34.88%)  31
General disorders   
Catheter site pain  1  3/43 (6.98%)  3
Chest pain  1  4/43 (9.30%)  4
Chills  1  3/43 (6.98%)  3
Fatigue  1  7/43 (16.28%)  10
Mucosal inflammation  1  4/43 (9.30%)  4
Oedema peripheral  1  4/43 (9.30%)  10
Pain  1  3/43 (6.98%)  3
Pyrexia  1  21/43 (48.84%)  35
Infections and infestations   
Bacteraemia  1  3/43 (6.98%)  3
Investigations   
Alanine aminotransferase increased  1  5/43 (11.63%)  9
Aspartate aminotransferase increased  1  6/43 (13.95%)  11
Blood creatinine increased  1  5/43 (11.63%)  20
Blood potassium decreased  1  3/43 (6.98%)  13
Platelet count decreased  1  8/43 (18.60%)  41
Weight decreased  1  3/43 (6.98%)  6
Metabolism and nutrition disorders   
Decreased appetite  1  9/43 (20.93%)  12
Fluid overload  1  3/43 (6.98%)  3
Hypercalcaemia  1  4/43 (9.30%)  14
Hyperglycaemia  1  5/43 (11.63%)  15
Hyperkalaemia  1  3/43 (6.98%)  5
Hypocalcaemia  1  6/43 (13.95%)  18
Hypokalaemia  1  9/43 (20.93%)  40
Hypomagnesaemia  1  8/43 (18.60%)  10
Hyponatraemia  1  6/43 (13.95%)  11
Hypophosphataemia  1  5/43 (11.63%)  15
Tumour lysis syndrome  1  4/43 (9.30%)  4
Musculoskeletal and connective tissue disorders   
Arthralgia  1  3/43 (6.98%)  3
Back pain  1  3/43 (6.98%)  5
Bone pain  1  3/43 (6.98%)  4
Pain in extremity  1  5/43 (11.63%)  8
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Acute lymphocytic leukaemia  1  4/43 (9.30%)  4
Acute myeloid leukaemia  1  3/43 (6.98%)  3
Nervous system disorders   
Dizziness  1  3/43 (6.98%)  3
Headache  1  9/43 (20.93%)  12
Psychiatric disorders   
Anxiety  1  3/43 (6.98%)  4
Respiratory, thoracic and mediastinal disorders   
Cough  1  12/43 (27.91%)  13
Dyspnoea  1  5/43 (11.63%)  6
Epistaxis  1  6/43 (13.95%)  6
Productive cough  1  3/43 (6.98%)  4
Pulmonary oedema  1  3/43 (6.98%)  4
Rhinorrhoea  1  3/43 (6.98%)  3
Skin and subcutaneous tissue disorders   
Dry skin  1  3/43 (6.98%)  4
Pruritus  1  4/43 (9.30%)  5
Rash  1  5/43 (11.63%)  7
Vascular disorders   
Hypertension  1  12/43 (27.91%)  19
Hypotension  1  8/43 (18.60%)  18
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
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
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Name/Title: Manager
Organization: Teva Pharmaceuticals USA
Phone: 1-866-384-5525
EMail: clinicaltrialqueries@tevausa.com
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Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT01088984     History of Changes
Other Study ID Numbers: C18083/2046
2010-020768-40 ( EudraCT Number )
First Submitted: March 16, 2010
First Posted: March 18, 2010
Results First Submitted: September 24, 2014
Results First Posted: October 1, 2014
Last Update Posted: May 23, 2016