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Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma

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ClinicalTrials.gov Identifier: NCT00026312
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : March 29, 2017
Last Update Posted : May 10, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Localized Resectable Neuroblastoma
Localized Unresectable Neuroblastoma
Recurrent Neuroblastoma
Regional Neuroblastoma
Stage 4 Neuroblastoma
Stage 4S Neuroblastoma
Interventions Biological: Aldesleukin
Biological: Dinutuximab
Drug: Isotretinoin
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Other: Quality-of-Life Assessment
Biological: Sargramostim
Enrollment 1449
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Regimen A Regimen B
Hide Arm/Group Description Randomized to Regimen A – RA Only Regimen B – RA + Immunotherapy
Period Title: Overall Study
Started 116 1333
Completed 82 1064
Not Completed 34 269
Reason Not Completed
Adverse Event             0             32
Death             1             7
Lack of Efficacy             19             114
Lost to Follow-up             0             5
Physician Decision             1             37
Protocol Violation             0             3
Withdrawal by Subject             1             6
Ineligible             4             5
Entry onto another COG study             0             1
Refusal by patient/parent/guardian             8             59
Arm/Group Title Regimen A Regimen B Total
Hide Arm/Group Description Randomized to Regimen A - RA Only Regimen B - RA + Immunotherapy Total of all reporting groups
Overall Number of Baseline Participants 116 1333 1449
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants 1333 participants 1449 participants
<=18 years
116
 100.0%
1325
  99.4%
1441
  99.4%
Between 18 and 65 years
0
   0.0%
8
   0.6%
8
   0.6%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 116 participants 1333 participants 1449 participants
3.22  (2.12) 3.64  (2.77) 3.61  (2.73)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants 1333 participants 1449 participants
Female
49
  42.2%
534
  40.1%
583
  40.2%
Male
67
  57.8%
799
  59.9%
866
  59.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants 1333 participants 1449 participants
Hispanic or Latino
11
   9.5%
142
  10.7%
153
  10.6%
Not Hispanic or Latino
99
  85.3%
1159
  86.9%
1258
  86.8%
Unknown or Not Reported
6
   5.2%
32
   2.4%
38
   2.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants 1333 participants 1449 participants
American Indian or Alaska Native
0
   0.0%
3
   0.2%
3
   0.2%
Asian
4
   3.4%
62
   4.7%
66
   4.6%
Native Hawaiian or Other Pacific Islander
2
   1.7%
2
   0.2%
4
   0.3%
Black or African American
8
   6.9%
153
  11.5%
161
  11.1%
White
89
  76.7%
942
  70.7%
1031
  71.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
13
  11.2%
171
  12.8%
184
  12.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 116 participants 1333 participants 1449 participants
New Zealand 0 17 17
Canada 13 135 148
United States 100 1092 1192
Australia 3 89 92
1.Primary Outcome
Title Event-Free Survival (EFS)
Hide Description Comparison to determine if RA + Immunotherapy improves EFS as compared to RA Only
Time Frame Three years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Eligible, randomized patients.
Arm/Group Title Regimen A Regimen B
Hide Arm/Group Description:
Randomized to Regimen A - RA Only
Randomized to Regimen B - RA + Immunotherapy
Overall Number of Participants Analyzed 112 114
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
48.1
(38.4 to 57.8)
62.9
(54.0 to 71.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regimen A, Regimen B
Comments The event-free survival distributions of patients randomized to Regimen A - RA Only and randomized to Regimen B - RA + Immunotherapy were compared using the log-rank test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1016
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Log Rank Test Statistic
Estimated Value 2.6803
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Event-Free Survival (EFS)
Hide Description Comparison to determine if RA + Immunotherapy improves EFS as compared to RA Only for the subgroup of randomized patients with INSS Stage 4 disease. Descriptive comparison of outcome data for patients with persistent disease documented by biopsy to historical data for the analogous patients from CCG-3981.
Time Frame Three years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Eligible, randomized patients with INSS Stage 4 disease. Eligible patients with persistent disease.
Arm/Group Title Regimen A Regimen B
Hide Arm/Group Description:
Randomized to Regimen A - RA Only
Regimen B - RA + Immunotherapy
Overall Number of Participants Analyzed 93 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Randomized patients with INSS Stage 4 disease Number Analyzed 93 participants 90 participants
43.2
(32.5 to 53.8)
59.7
(49.5 to 69.9)
Eligible patients with persistent disease Number Analyzed 0 participants 37 participants
35.1
(19.8 to 50.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regimen A, Regimen B
Comments The event-free survival distributions of patients randomized to Regimen A - RA Only and randomized to Regimen B - RA + Immunotherapy for the subgroup of patients with INSS Stage 4 disease were compared using the log-rank test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1057
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Log Rank Test Statistic
Estimated Value 2.6176
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Event-Free Survival (EFS) of Patients From the Non-randomized Portion of the Trial
Hide Description EFS for patients receiving RA + Immunotherapy following the cessation of the randomized portion of the study.
Time Frame Three years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Eligible patients non-randomly assigned to Regimen B after halting of randomization, excluding patients with persistent disease.
Arm/Group Title Regimen B
Hide Arm/Group Description:
Non-randomly assigned to Regimen B after halting of randomization, excluding patients with persistent disease
Overall Number of Participants Analyzed 1177
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
64.0
(60.2 to 67.8)
4.Secondary Outcome
Title Incidence of Toxicities Assessed Using Common Terminology Criteria for Adverse Events Version 4.0
Hide Description Proportion of patients experiencing at least one Grade 3 or higher toxicity.
Time Frame From enrollment to follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Eligible patients enrolled prior to halting of randomization.
Arm/Group Title Regimen A Regimen B
Hide Arm/Group Description:
Randomized to Regimen A - RA Only
Patients that received RA + Immunotherapy before halting of randomization
Overall Number of Participants Analyzed 112 141
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion
0.64
(0.55 to 0.73)
0.94
(0.90 to 0.98)
5.Secondary Outcome
Title Number of Courses of Therapy Delivered
Hide Description Number of courses of therapy delivered for patients randomized to RA + Immunotherapy vs. patients non-randomly assigned to RA + Immunotherapy, excluding patients with persistent disease.
Time Frame Courses 1-6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Eligible patients assigned to Regimen B, excluding patients with persistent disease.
Arm/Group Title Regimen B
Hide Arm/Group Description:
Regimen B- RA + Immunotherapy
Overall Number of Participants Analyzed 1291
Median (Full Range)
Unit of Measure: courses per patient
Randomized to Regimen B - RA + Immunotherapy
6
(0 to 6)
Non-randomly assigned after halting randomization
6
(0 to 6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regimen B
Comments The number of courses of therapy delivered or patients randomized to Regimen B - RA + Immunotherapy and non-randomly assigned to Regimen B after halting of randomization, excluding patients with persistent disease, were compared using the Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0262
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Overall Survival (OS)
Hide Description Comparison to determine if RA + Immunotherapy improves OS as compared to RA Only. Comparison to determine if RA + Immunotherapy improves OS as compared to RA only and for the subgroup of randomized patients with INSS Stage 4 disease.
Time Frame Three years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Eligible, randomized patients. Eligible, randomized patients with INSS Stage 4 disease.
Arm/Group Title Regimen A Regimen B
Hide Arm/Group Description:
Randomized to Regimen A - RA Only
Randomized to Regimen B - RA + Immunotherapy
Overall Number of Participants Analyzed 112 114
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Randomized patients Number Analyzed 112 participants 114 participants
67.4
(58.3 to 76.5)
78.8
(71.2 to 86.4)
Randomized patients with INSS Stage 4 disease Number Analyzed 93 participants 90 participants
64.0
(53.8 to 74.3)
78.7
(70.2 to 87.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regimen A, Regimen B
Comments The overall survival distributions of patients randomized to Regimen A - RA Only and randomized to Regimen B - RA + Immunotherapy were compared using the log-rank test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0634
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Log Rank Test Statistic
Estimated Value 3.4471
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regimen A, Regimen B
Comments The overall survival distributions of patients randomized to Regimen A - RA Only and randomized to Regimen B - RA + Immunotherapy for the subgroup of patients with INSS Stage 4 disease were compared using the log-rank test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.042
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Rank Test Statistic
Estimated Value 4.1362
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Overall Survival (OS) of Patients From the Non-randomized Portion of the Trial
Hide Description OS for patients receiving RA + Immunotherapy following the cessation of the randomized portion of the study.
Time Frame Three years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Eligible patients non-randomly assigned to Regimen B after halting of randomization, excluding patients with persistent disease
Arm/Group Title Regimen B
Hide Arm/Group Description:
Non-randomly assigned to Regimen B after halting of randomization, excluding patients with persistent disease
Overall Number of Participants Analyzed 1177
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
78.4
(75.1 to 81.6)
8.Other Pre-specified Outcome
Title Average Level of HACA
Hide Description The average level of HACA at each collection time point during immunotherapy will be calculated.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
9.Other Pre-specified Outcome
Title Cardiac Repolarization
Hide Description In general, descriptive summaries will include n, mean, standard deviation, median, minimum, maximum and 90% confidence intervals for continuous variables, and n and percent for categorical variables. Summaries will present data by assessment time when appropriate.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title Change in MRD
Hide Description A descriptive analysis of the change from baseline of MRD will be performed. Also, a Wilcoxon rank-sum test will be performed to compare the median change from baseline of MRD between the two treatment arms. A multivariate Cox proportional hazards regression model will test to see if the change in MRD burden is associated with EFS or OS.
Time Frame Baseline to up to 10 years
Outcome Measure Data Not Reported
11.Other Pre-specified Outcome
Title Change in Tumor Biology
Hide Description A multivariate Cox proportional hazards regression model will test to see if the dinutuximab serum level, HACA titer, effector cell function, or serum marker for effector cell activation are associated with EFS or OS.
Time Frame Baseline to up to 10 years
Outcome Measure Data Not Reported
12.Other Pre-specified Outcome
Title Circulating B7-H6 Levels
Hide Description Kaplan-Meier plots of EFS and OS will be generated after dichotomization using the median value for the cohort. To determine the prognostic value of circulating B7-H6 level, univariate analysis will be performed using a log rank test for EFS and OS. In multivariable analysis of EFS and OS, Cox models will be used to test for the independent prognostic ability of circulating B7-H6 level, adjusting for significant prognostic factors including MYCN status, INSS stage, histology and age at diagnosis.
Time Frame 1 week before first sargramostim injection (day -1 of course 1)
Outcome Measure Data Not Reported
13.Other Pre-specified Outcome
Title Genotype of FcR
Hide Description Kaplan-Meier plots of EFS will be generated for the three genotype subgroups of FcR as well as for the three genotype subgroups of Kir/Kir-ligand. In addition, a log rank test comparison will be made in a pairwise fashion of each of the genotypes within FcR and within Kir/Kir-ligand.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
14.Other Pre-specified Outcome
Title Genotype of Kir/Kir-ligand
Hide Description Kaplan-Meier plots of EFS will be generated for the three genotype subgroups of FcR as well as for the three genotype subgroups of Kir/Kir-ligand. In addition, a log rank test comparison will be made in a pairwise fashion of each of the genotypes within FcR and within Kir/Kir-ligand.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
15.Other Pre-specified Outcome
Title Isotretinoin Pharmacokinetic Parameters
Hide Description To determine if there is a relationship of the peak serum concentration level with EFS, the term for this level will be tested in a Cox proportional hazards model. To determine if there is a relationship of the peak serum concentration level with toxicity rates, Kendall’s Tau statistic will be calculated.
Time Frame At 4 hours after administration on day 14 of course 1
Outcome Measure Data Not Reported
16.Other Pre-specified Outcome
Title Levels of ADCC
Hide Description Will be descriptively compared.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
17.Other Pre-specified Outcome
Title NKp30 Isoform Expression and SNP
Hide Description Kaplan-Meier plots of EFS and OS will be generated after dichotomization using the median value for the cohort. To determine the prognostic value of NKp30 isoform expression and SNP, univariate analysis will be performed using a log rank test for EFS and OS. In multivariable analysis of EFS and OS, Cox models will be used to test for the independent prognostic ability of NKp30 isoform expression and SNP, adjusting for significant prognostic factors including v-MYC myelocytomatosis viral related oncogene, neuroblastoma derived (avian) (MYCN) status, INSS stage, histology and age at diagnosis.
Time Frame 1 week before first sargramostim injection (day -1 of course 1)
Outcome Measure Data Not Reported
18.Other Pre-specified Outcome
Title Presence of Naturally Occurring Anti-glycan Antibodies
Hide Description A Fisher’s exact test will be performed to determine if the presence of naturally occurring anti-glycan antibodies correlates with allergic reactions. A Wilcoxon test will be performed to determine if the presence of naturally occurring anti-glycan antibodies correlates with blood levels of dinutuximab.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description Ineligible patients were excluded from the adverse event analysis, so only eligible patients are reported.
 
Arm/Group Title Regimen A Regimen B
Hide Arm/Group Description Randomized to Regimen A - RA Only Regimen B – RA + Immunotherapy
All-Cause Mortality
Regimen A Regimen B
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Regimen A Regimen B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/112 (8.93%)      785/1328 (59.11%)    
Blood and lymphatic system disorders     
Anemia  0/112 (0.00%)  0 42/1328 (3.16%)  49
Blood and lymphatic system disorders - Other specify  0/112 (0.00%)  0 3/1328 (0.23%)  3
Disseminated intravascular coagulation  0/112 (0.00%)  0 3/1328 (0.23%)  3
Febrile neutropenia  0/112 (0.00%)  0 4/1328 (0.30%)  4
Hemolysis  0/112 (0.00%)  0 2/1328 (0.15%)  2
Hemolytic uremic syndrome  0/112 (0.00%)  0 2/1328 (0.15%)  2
Cardiac disorders     
Atrial fibrillation  0/112 (0.00%)  0 1/1328 (0.08%)  2
Cardiac arrest  0/112 (0.00%)  0 3/1328 (0.23%)  3
Cardiac disorders - Other specify  1/112 (0.89%)  1 5/1328 (0.38%)  5
Heart failure  0/112 (0.00%)  0 3/1328 (0.23%)  3
Left ventricular systolic dysfunction  0/112 (0.00%)  0 7/1328 (0.53%)  7
Pericardial effusion  0/112 (0.00%)  0 3/1328 (0.23%)  3
Right ventricular dysfunction  0/112 (0.00%)  0 1/1328 (0.08%)  1
Sinus bradycardia  0/112 (0.00%)  0 2/1328 (0.15%)  2
Sinus tachycardia  0/112 (0.00%)  0 13/1328 (0.98%)  16
Supraventricular tachycardia  0/112 (0.00%)  0 1/1328 (0.08%)  1
Ventricular arrhythmia  0/112 (0.00%)  0 2/1328 (0.15%)  2
Ear and labyrinth disorders     
Ear and labyrinth disorders - Other specify  0/112 (0.00%)  0 1/1328 (0.08%)  1
Ear pain  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hearing impaired  0/112 (0.00%)  0 1/1328 (0.08%)  1
Endocrine disorders     
Adrenal insufficiency  0/112 (0.00%)  0 1/1328 (0.08%)  1
Endocrine disorders - Other specify  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hypothyroidism  0/112 (0.00%)  0 4/1328 (0.30%)  4
Eye disorders     
Blurred vision  0/112 (0.00%)  0 7/1328 (0.53%)  7
Eye disorders - Other specify  1/112 (0.89%)  1 16/1328 (1.20%)  16
Optic nerve disorder  0/112 (0.00%)  0 2/1328 (0.15%)  2
Papilledema  0/112 (0.00%)  0 2/1328 (0.15%)  2
Photophobia  0/112 (0.00%)  0 5/1328 (0.38%)  5
Gastrointestinal disorders     
Abdominal distension  0/112 (0.00%)  0 7/1328 (0.53%)  7
Abdominal pain  0/112 (0.00%)  0 41/1328 (3.09%)  60
Ascites  0/112 (0.00%)  0 5/1328 (0.38%)  5
Colitis  0/112 (0.00%)  0 9/1328 (0.68%)  10
Colonic obstruction  0/112 (0.00%)  0 2/1328 (0.15%)  2
Diarrhea  0/112 (0.00%)  0 35/1328 (2.64%)  36
Duodenal obstruction  0/112 (0.00%)  0 1/1328 (0.08%)  1
Esophageal hemorrhage  0/112 (0.00%)  0 1/1328 (0.08%)  1
Esophageal perforation  0/112 (0.00%)  0 1/1328 (0.08%)  1
Esophageal stenosis  0/112 (0.00%)  0 3/1328 (0.23%)  3
Esophageal ulcer  0/112 (0.00%)  0 1/1328 (0.08%)  1
Esophagitis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Gastric hemorrhage  0/112 (0.00%)  0 3/1328 (0.23%)  3
Gastritis  0/112 (0.00%)  0 2/1328 (0.15%)  2
Gastrointestinal disorders - Other specify  0/112 (0.00%)  0 2/1328 (0.15%)  3
Gastrointestinal fistula  0/112 (0.00%)  0 1/1328 (0.08%)  1
Ileal obstruction  0/112 (0.00%)  0 1/1328 (0.08%)  1
Ileus  0/112 (0.00%)  0 10/1328 (0.75%)  10
Intra-abdominal hemorrhage  0/112 (0.00%)  0 1/1328 (0.08%)  1
Jejunal obstruction  0/112 (0.00%)  0 2/1328 (0.15%)  2
Lower gastrointestinal hemorrhage  0/112 (0.00%)  0 1/1328 (0.08%)  1
Malabsorption  0/112 (0.00%)  0 1/1328 (0.08%)  1
Nausea  1/112 (0.89%)  1 3/1328 (0.23%)  3
Proctitis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Rectal hemorrhage  0/112 (0.00%)  0 1/1328 (0.08%)  1
Small intestinal obstruction  1/112 (0.89%)  1 4/1328 (0.30%)  4
Typhlitis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Vomiting  1/112 (0.89%)  1 14/1328 (1.05%)  16
General disorders     
Chills  0/112 (0.00%)  0 5/1328 (0.38%)  5
Death NOS  0/112 (0.00%)  0 3/1328 (0.23%)  3
Edema face  0/112 (0.00%)  0 12/1328 (0.90%)  13
Edema limbs  0/112 (0.00%)  0 2/1328 (0.15%)  2
Edema trunk  0/112 (0.00%)  0 3/1328 (0.23%)  3
Fatigue  0/112 (0.00%)  0 8/1328 (0.60%)  8
Fever  0/112 (0.00%)  0 121/1328 (9.11%)  148
Flu like symptoms  0/112 (0.00%)  0 1/1328 (0.08%)  1
Gait disturbance  0/112 (0.00%)  0 1/1328 (0.08%)  1
General disorders and administration site conditions - Other specify  0/112 (0.00%)  0 4/1328 (0.30%)  4
Infusion related reaction  0/112 (0.00%)  0 4/1328 (0.30%)  4
Injection site reaction  0/112 (0.00%)  0 2/1328 (0.15%)  2
Irritability  0/112 (0.00%)  0 6/1328 (0.45%)  6
Localized edema  0/112 (0.00%)  0 1/1328 (0.08%)  1
Non-cardiac chest pain  0/112 (0.00%)  0 6/1328 (0.45%)  6
Pain  0/112 (0.00%)  0 47/1328 (3.54%)  68
Hepatobiliary disorders     
Hepatic failure  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hepatobiliary disorders - Other specify  0/112 (0.00%)  0 1/1328 (0.08%)  1
Immune system disorders     
Allergic reaction  1/112 (0.89%)  3 141/1328 (10.62%)  185
Anaphylaxis  1/112 (0.89%)  1 153/1328 (11.52%)  180
Cytokine release syndrome  0/112 (0.00%)  0 23/1328 (1.73%)  35
Immune system disorders - Other specify  0/112 (0.00%)  0 1/1328 (0.08%)  1
Serum sickness  0/112 (0.00%)  0 5/1328 (0.38%)  7
Infections and infestations     
Abdominal infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Anorectal infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Bladder infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Bone infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Bronchial infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Catheter related infection  1/112 (0.89%)  1 88/1328 (6.63%)  105
Device related infection  0/112 (0.00%)  0 4/1328 (0.30%)  4
Enterocolitis infectious  0/112 (0.00%)  0 11/1328 (0.83%)  11
Eye infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Infections and infestations - Other specify  0/112 (0.00%)  0 113/1328 (8.51%)  145
Kidney infection  0/112 (0.00%)  0 2/1328 (0.15%)  2
Lung infection  0/112 (0.00%)  0 13/1328 (0.98%)  14
Mucosal infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Otitis externa  0/112 (0.00%)  0 1/1328 (0.08%)  1
Peripheral nerve infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Sepsis  0/112 (0.00%)  0 33/1328 (2.48%)  35
Skin infection  0/112 (0.00%)  0 4/1328 (0.30%)  4
Upper respiratory infection  0/112 (0.00%)  0 9/1328 (0.68%)  10
Urinary tract infection  0/112 (0.00%)  0 11/1328 (0.83%)  13
Wound infection  0/112 (0.00%)  0 2/1328 (0.15%)  2
Injury, poisoning and procedural complications     
Fracture  0/112 (0.00%)  0 2/1328 (0.15%)  2
Vascular access complication  0/112 (0.00%)  0 2/1328 (0.15%)  2
Investigations     
Activated partial thromboplastin time prolonged  0/112 (0.00%)  0 2/1328 (0.15%)  2
Alanine aminotransferase increased  2/112 (1.79%)  3 36/1328 (2.71%)  45
Alkaline phosphatase increased  0/112 (0.00%)  0 6/1328 (0.45%)  7
Aspartate aminotransferase increased  1/112 (0.89%)  1 28/1328 (2.11%)  30
Blood bilirubin increased  0/112 (0.00%)  0 21/1328 (1.58%)  21
Cardiac troponin I increased  0/112 (0.00%)  0 1/1328 (0.08%)  1
Creatinine increased  0/112 (0.00%)  0 14/1328 (1.05%)  15
Fibrinogen decreased  0/112 (0.00%)  0 2/1328 (0.15%)  2
GGT increased  0/112 (0.00%)  0 14/1328 (1.05%)  18
INR increased  0/112 (0.00%)  0 2/1328 (0.15%)  2
Investigations - Other specify  0/112 (0.00%)  0 5/1328 (0.38%)  5
Lipase increased  0/112 (0.00%)  0 3/1328 (0.23%)  3
Lymphocyte count decreased  2/112 (1.79%)  2 17/1328 (1.28%)  22
Neutrophil count decreased  0/112 (0.00%)  0 30/1328 (2.26%)  31
Platelet count decreased  0/112 (0.00%)  0 29/1328 (2.18%)  44
Serum amylase increased  0/112 (0.00%)  0 2/1328 (0.15%)  2
Urine output decreased  0/112 (0.00%)  0 27/1328 (2.03%)  37
Weight gain  0/112 (0.00%)  0 8/1328 (0.60%)  8
Weight loss  0/112 (0.00%)  0 5/1328 (0.38%)  6
White blood cell decreased  0/112 (0.00%)  0 15/1328 (1.13%)  17
Metabolism and nutrition disorders     
Acidosis  0/112 (0.00%)  0 10/1328 (0.75%)  10
Anorexia  0/112 (0.00%)  0 16/1328 (1.20%)  18
Dehydration  0/112 (0.00%)  0 22/1328 (1.66%)  22
Hypercalcemia  0/112 (0.00%)  0 24/1328 (1.81%)  35
Hyperglycemia  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hyperkalemia  0/112 (0.00%)  0 10/1328 (0.75%)  10
Hypermagnesemia  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hypernatremia  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hypertriglyceridemia  1/112 (0.89%)  1 6/1328 (0.45%)  6
Hypoalbuminemia  0/112 (0.00%)  0 23/1328 (1.73%)  25
Hypocalcemia  0/112 (0.00%)  0 23/1328 (1.73%)  25
Hypoglycemia  0/112 (0.00%)  0 6/1328 (0.45%)  6
Hypokalemia  0/112 (0.00%)  0 65/1328 (4.89%)  71
Hypomagnesemia  0/112 (0.00%)  0 4/1328 (0.30%)  5
Hyponatremia  0/112 (0.00%)  0 66/1328 (4.97%)  76
Hypophosphatemia  0/112 (0.00%)  0 38/1328 (2.86%)  40
Musculoskeletal and connective tissue disorders     
Arthralgia  0/112 (0.00%)  0 5/1328 (0.38%)  8
Back pain  0/112 (0.00%)  0 9/1328 (0.68%)  12
Bone pain  0/112 (0.00%)  0 4/1328 (0.30%)  4
Chest wall pain  0/112 (0.00%)  0 3/1328 (0.23%)  3
Muscle weakness lower limb  0/112 (0.00%)  0 2/1328 (0.15%)  2
Musculoskeletal and connective tissue disorder - Other specify  0/112 (0.00%)  0 2/1328 (0.15%)  2
Myalgia  0/112 (0.00%)  0 1/1328 (0.08%)  1
Neck pain  0/112 (0.00%)  0 1/1328 (0.08%)  1
Pain in extremity  0/112 (0.00%)  0 20/1328 (1.51%)  29
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasms benign malignant and unspecified (incl cysts and polyps) - Other specify  0/112 (0.00%)  0 4/1328 (0.30%)  4
Nervous system disorders     
Depressed level of consciousness  0/112 (0.00%)  0 7/1328 (0.53%)  7
Dysphasia  0/112 (0.00%)  0 1/1328 (0.08%)  1
Encephalopathy  0/112 (0.00%)  0 3/1328 (0.23%)  3
Extrapyramidal disorder  0/112 (0.00%)  0 2/1328 (0.15%)  2
Headache  0/112 (0.00%)  0 11/1328 (0.83%)  12
Hydrocephalus  0/112 (0.00%)  0 4/1328 (0.30%)  4
Intracranial hemorrhage  0/112 (0.00%)  0 6/1328 (0.45%)  6
Myelitis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Nervous system disorders - Other specify  0/112 (0.00%)  0 1/1328 (0.08%)  1
Neuralgia  0/112 (0.00%)  0 11/1328 (0.83%)  12
Oculomotor nerve disorder  0/112 (0.00%)  0 1/1328 (0.08%)  1
Peripheral motor neuropathy  0/112 (0.00%)  0 4/1328 (0.30%)  4
Peripheral sensory neuropathy  0/112 (0.00%)  0 5/1328 (0.38%)  5
Reversible posterior leukoencephalopathy syndrome  0/112 (0.00%)  0 3/1328 (0.23%)  3
Seizure  0/112 (0.00%)  0 10/1328 (0.75%)  10
Somnolence  0/112 (0.00%)  0 1/1328 (0.08%)  1
Syncope  0/112 (0.00%)  0 1/1328 (0.08%)  1
Tremor  0/112 (0.00%)  0 1/1328 (0.08%)  1
Psychiatric disorders     
Agitation  0/112 (0.00%)  0 3/1328 (0.23%)  3
Anxiety  0/112 (0.00%)  0 1/1328 (0.08%)  1
Confusion  0/112 (0.00%)  0 1/1328 (0.08%)  1
Delirium  0/112 (0.00%)  0 2/1328 (0.15%)  2
Depression  0/112 (0.00%)  0 1/1328 (0.08%)  1
Euphoria  0/112 (0.00%)  0 1/1328 (0.08%)  1
Insomnia  0/112 (0.00%)  0 1/1328 (0.08%)  1
Personality change  0/112 (0.00%)  0 1/1328 (0.08%)  1
Psychosis  0/112 (0.00%)  0 3/1328 (0.23%)  3
Suicidal ideation  0/112 (0.00%)  0 1/1328 (0.08%)  1
Suicide attempt  0/112 (0.00%)  0 1/1328 (0.08%)  1
Renal and urinary disorders     
Acute kidney injury  0/112 (0.00%)  0 12/1328 (0.90%)  12
Chronic kidney disease  0/112 (0.00%)  0 2/1328 (0.15%)  2
Proteinuria  0/112 (0.00%)  0 9/1328 (0.68%)  12
Renal and urinary disorders - Other specify  0/112 (0.00%)  0 3/1328 (0.23%)  4
Urinary frequency  0/112 (0.00%)  0 1/1328 (0.08%)  1
Urinary retention  0/112 (0.00%)  0 10/1328 (0.75%)  11
Urinary tract obstruction  0/112 (0.00%)  0 1/1328 (0.08%)  1
Reproductive system and breast disorders     
Scrotal pain  0/112 (0.00%)  0 1/1328 (0.08%)  1
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome  0/112 (0.00%)  0 11/1328 (0.83%)  12
Allergic rhinitis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Apnea  0/112 (0.00%)  0 6/1328 (0.45%)  6
Aspiration  0/112 (0.00%)  0 1/1328 (0.08%)  1
Atelectasis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Bronchial obstruction  0/112 (0.00%)  0 1/1328 (0.08%)  1
Bronchopulmonary hemorrhage  0/112 (0.00%)  0 2/1328 (0.15%)  2
Bronchospasm  0/112 (0.00%)  0 30/1328 (2.26%)  34
Cough  0/112 (0.00%)  0 16/1328 (1.20%)  18
Dyspnea  0/112 (0.00%)  0 53/1328 (3.99%)  60
Epistaxis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hypoxia  0/112 (0.00%)  0 69/1328 (5.20%)  85
Laryngeal edema  0/112 (0.00%)  0 3/1328 (0.23%)  5
Pharyngolaryngeal pain  0/112 (0.00%)  0 1/1328 (0.08%)  1
Pleural effusion  0/112 (0.00%)  0 8/1328 (0.60%)  8
Pleural hemorrhage  0/112 (0.00%)  0 1/1328 (0.08%)  1
Pleuritic pain  0/112 (0.00%)  0 1/1328 (0.08%)  1
Pneumonitis  0/112 (0.00%)  0 2/1328 (0.15%)  2
Pneumothorax  0/112 (0.00%)  0 1/1328 (0.08%)  1
Pulmonary edema  0/112 (0.00%)  0 10/1328 (0.75%)  10
Respiratory thoracic and mediastinal disorders - Other specify  0/112 (0.00%)  0 5/1328 (0.38%)  5
Respiratory failure  0/112 (0.00%)  0 7/1328 (0.53%)  7
Stridor  0/112 (0.00%)  0 6/1328 (0.45%)  7
Wheezing  0/112 (0.00%)  0 6/1328 (0.45%)  6
Skin and subcutaneous tissue disorders     
Dry skin  0/112 (0.00%)  0 2/1328 (0.15%)  2
Erythema multiforme  1/112 (0.89%)  1 4/1328 (0.30%)  4
Hyperhidrosis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Pain of skin  0/112 (0.00%)  0 1/1328 (0.08%)  1
Periorbital edema  0/112 (0.00%)  0 2/1328 (0.15%)  2
Pruritus  0/112 (0.00%)  0 10/1328 (0.75%)  10
Rash acneiform  0/112 (0.00%)  0 1/1328 (0.08%)  1
Rash maculo-papular  0/112 (0.00%)  0 6/1328 (0.45%)  6
Skin and subcutaneous tissue disorders - Other specify  0/112 (0.00%)  0 3/1328 (0.23%)  3
Urticaria  0/112 (0.00%)  0 102/1328 (7.68%)  128
Surgical and medical procedures     
Surgical and medical procedures - Other specify  0/112 (0.00%)  0 1/1328 (0.08%)  1
Vascular disorders     
Capillary leak syndrome  0/112 (0.00%)  0 154/1328 (11.60%)  189
Hypertension  0/112 (0.00%)  0 22/1328 (1.66%)  24
Hypotension  0/112 (0.00%)  0 249/1328 (18.75%)  335
Thromboembolic event  0/112 (0.00%)  0 4/1328 (0.30%)  4
Vascular disorders - Other specify  0/112 (0.00%)  0 2/1328 (0.15%)  2
1
Term from vocabulary, CTCv4
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Regimen A Regimen B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   92/112 (82.14%)      1244/1328 (93.67%)    
Blood and lymphatic system disorders     
Anemia  22/112 (19.64%)  47 428/1328 (32.23%)  962
Blood and lymphatic system disorders - Other specify  1/112 (0.89%)  1 16/1328 (1.20%)  24
Disseminated intravascular coagulation  0/112 (0.00%)  0 3/1328 (0.23%)  3
Febrile neutropenia  0/112 (0.00%)  0 19/1328 (1.43%)  23
Hemolytic uremic syndrome  0/112 (0.00%)  0 1/1328 (0.08%)  1
Cardiac disorders     
Atrial fibrillation  0/112 (0.00%)  0 1/1328 (0.08%)  1
Cardiac disorders - Other specify  1/112 (0.89%)  1 36/1328 (2.71%)  49
Chest pain - cardiac  0/112 (0.00%)  0 2/1328 (0.15%)  2
Conduction disorder  0/112 (0.00%)  0 1/1328 (0.08%)  1
Heart failure  0/112 (0.00%)  0 1/1328 (0.08%)  1
Left ventricular systolic dysfunction  0/112 (0.00%)  0 1/1328 (0.08%)  1
Mobitz type I  0/112 (0.00%)  0 1/1328 (0.08%)  1
Paroxysmal atrial tachycardia  0/112 (0.00%)  0 5/1328 (0.38%)  6
Pericardial effusion  1/112 (0.89%)  1 1/1328 (0.08%)  1
Sinus bradycardia  0/112 (0.00%)  0 2/1328 (0.15%)  4
Sinus tachycardia  1/112 (0.89%)  1 49/1328 (3.69%)  82
Supraventricular tachycardia  0/112 (0.00%)  0 8/1328 (0.60%)  13
Ventricular arrhythmia  0/112 (0.00%)  0 2/1328 (0.15%)  2
Ventricular tachycardia  0/112 (0.00%)  0 3/1328 (0.23%)  3
Ear and labyrinth disorders     
Ear and labyrinth disorders - Other specify  0/112 (0.00%)  0 2/1328 (0.15%)  2
Ear pain  1/112 (0.89%)  1 3/1328 (0.23%)  3
External ear inflammation  1/112 (0.89%)  1 0/1328 (0.00%)  0
Hearing impaired  6/112 (5.36%)  8 22/1328 (1.66%)  28
Middle ear inflammation  1/112 (0.89%)  1 1/1328 (0.08%)  1
Tinnitus  0/112 (0.00%)  0 1/1328 (0.08%)  1
Endocrine disorders     
Adrenal insufficiency  0/112 (0.00%)  0 3/1328 (0.23%)  3
Endocrine disorders - Other specify  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hyperthyroidism  0/112 (0.00%)  0 4/1328 (0.30%)  6
Hypothyroidism  2/112 (1.79%)  2 6/1328 (0.45%)  6
Eye disorders     
Blurred vision  0/112 (0.00%)  0 12/1328 (0.90%)  14
Conjunctivitis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Dry eye  1/112 (0.89%)  1 2/1328 (0.15%)  2
Extraocular muscle paresis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Eye disorders - Other specify  2/112 (1.79%)  2 20/1328 (1.51%)  24
Eye pain  0/112 (0.00%)  0 2/1328 (0.15%)  3
Flashing lights  0/112 (0.00%)  0 1/1328 (0.08%)  1
Photophobia  2/112 (1.79%)  3 8/1328 (0.60%)  8
Watering eyes  0/112 (0.00%)  0 1/1328 (0.08%)  2
Gastrointestinal disorders     
Abdominal distension  0/112 (0.00%)  0 9/1328 (0.68%)  9
Abdominal pain  11/112 (9.82%)  14 312/1328 (23.49%)  566
Anal mucositis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Anal pain  0/112 (0.00%)  0 4/1328 (0.30%)  4
Cheilitis  4/112 (3.57%)  7 16/1328 (1.20%)  29
Colitis  0/112 (0.00%)  0 11/1328 (0.83%)  14
Colonic stenosis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Constipation  2/112 (1.79%)  2 24/1328 (1.81%)  35
Diarrhea  16/112 (14.29%)  26 196/1328 (14.76%)  311
Dry mouth  0/112 (0.00%)  0 1/1328 (0.08%)  1
Dysphagia  0/112 (0.00%)  0 1/1328 (0.08%)  1
Esophageal stenosis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Esophagitis  0/112 (0.00%)  0 2/1328 (0.15%)  2
Flatulence  0/112 (0.00%)  0 1/1328 (0.08%)  1
Gastric ulcer  0/112 (0.00%)  0 1/1328 (0.08%)  1
Gastritis  0/112 (0.00%)  0 3/1328 (0.23%)  3
Gastrointestinal disorders - Other specify  0/112 (0.00%)  0 5/1328 (0.38%)  6
Gastrointestinal pain  0/112 (0.00%)  0 1/1328 (0.08%)  1
Gastroparesis  0/112 (0.00%)  0 1/1328 (0.08%)  6
Gingival pain  0/112 (0.00%)  0 1/1328 (0.08%)  1
Ileus  0/112 (0.00%)  0 3/1328 (0.23%)  3
Lower gastrointestinal hemorrhage  0/112 (0.00%)  0 2/1328 (0.15%)  2
Malabsorption  0/112 (0.00%)  0 2/1328 (0.15%)  5
Mucositis oral  1/112 (0.89%)  1 6/1328 (0.45%)  6
Nausea  2/112 (1.79%)  2 40/1328 (3.01%)  65
Oral pain  0/112 (0.00%)  0 8/1328 (0.60%)  9
Pancreatitis  1/112 (0.89%)  1 0/1328 (0.00%)  0
Rectal hemorrhage  0/112 (0.00%)  0 2/1328 (0.15%)  2
Rectal pain  1/112 (0.89%)  1 4/1328 (0.30%)  4
Small intestinal obstruction  0/112 (0.00%)  0 4/1328 (0.30%)  4
Stomach pain  1/112 (0.89%)  1 16/1328 (1.20%)  23
Toothache  0/112 (0.00%)  0 3/1328 (0.23%)  3
Upper gastrointestinal hemorrhage  0/112 (0.00%)  0 1/1328 (0.08%)  1
Vomiting  21/112 (18.75%)  35 109/1328 (8.21%)  196
General disorders     
Chills  0/112 (0.00%)  0 31/1328 (2.33%)  43
Edema face  0/112 (0.00%)  0 49/1328 (3.69%)  82
Edema limbs  0/112 (0.00%)  0 20/1328 (1.51%)  28
Edema trunk  0/112 (0.00%)  0 3/1328 (0.23%)  3
Facial pain  1/112 (0.89%)  1 3/1328 (0.23%)  3
Fatigue  2/112 (1.79%)  3 33/1328 (2.48%)  39
Fever  33/112 (29.46%)  43 536/1328 (40.36%)  991
Flu like symptoms  0/112 (0.00%)  0 1/1328 (0.08%)  1
Gait disturbance  0/112 (0.00%)  0 4/1328 (0.30%)  4
General disorders and administration site conditions - Other specify  0/112 (0.00%)  0 6/1328 (0.45%)  8
Hypothermia  0/112 (0.00%)  0 2/1328 (0.15%)  2
Infusion site extravasation  0/112 (0.00%)  0 1/1328 (0.08%)  1
Injection site reaction  0/112 (0.00%)  0 10/1328 (0.75%)  13
Irritability  0/112 (0.00%)  0 13/1328 (0.98%)  17
Localized edema  0/112 (0.00%)  0 1/1328 (0.08%)  1
Non-cardiac chest pain  0/112 (0.00%)  0 10/1328 (0.75%)  12
Pain  6/112 (5.36%)  14 441/1328 (33.21%)  941
Hepatobiliary disorders     
Cholecystitis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hepatobiliary disorders - Other specify  0/112 (0.00%)  0 3/1328 (0.23%)  3
Immune system disorders     
Allergic reaction  11/112 (9.82%)  29 655/1328 (49.32%)  1405
Anaphylaxis  1/112 (0.89%)  2 71/1328 (5.35%)  92
Cytokine release syndrome  1/112 (0.89%)  1 115/1328 (8.66%)  205
Immune system disorders - Other specify  0/112 (0.00%)  0 4/1328 (0.30%)  4
Serum sickness  1/112 (0.89%)  1 0/1328 (0.00%)  0
Infections and infestations     
Abdominal infection  2/112 (1.79%)  2 8/1328 (0.60%)  11
Anorectal infection  0/112 (0.00%)  0 4/1328 (0.30%)  4
Bladder infection  0/112 (0.00%)  0 2/1328 (0.15%)  2
Bone infection  0/112 (0.00%)  0 3/1328 (0.23%)  3
Bronchial infection  2/112 (1.79%)  2 1/1328 (0.08%)  1
Catheter related infection  8/112 (7.14%)  9 97/1328 (7.30%)  128
Cecal infection  0/112 (0.00%)  0 2/1328 (0.15%)  2
Conjunctivitis infective  0/112 (0.00%)  0 1/1328 (0.08%)  1
Device related infection  1/112 (0.89%)  1 7/1328 (0.53%)  8
Endocarditis infective  0/112 (0.00%)  0 1/1328 (0.08%)  1
Enterocolitis infectious  2/112 (1.79%)  2 39/1328 (2.94%)  47
Esophageal infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Eye infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Gum infection  1/112 (0.89%)  1 1/1328 (0.08%)  1
Infections and infestations - Other specify  29/112 (25.89%)  42 147/1328 (11.07%)  255
Joint infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Lung infection  2/112 (1.79%)  2 13/1328 (0.98%)  13
Lymph gland infection  1/112 (0.89%)  1 1/1328 (0.08%)  1
Nail infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Otitis externa  0/112 (0.00%)  0 1/1328 (0.08%)  1
Otitis media  1/112 (0.89%)  1 6/1328 (0.45%)  6
Ovarian infection  1/112 (0.89%)  1 0/1328 (0.00%)  0
Pelvic infection  1/112 (0.89%)  1 0/1328 (0.00%)  0
Peripheral nerve infection  1/112 (0.89%)  2 1/1328 (0.08%)  1
Pharyngitis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Pleural infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Rash pustular  0/112 (0.00%)  0 1/1328 (0.08%)  1
Rhinitis infective  0/112 (0.00%)  0 3/1328 (0.23%)  4
Salivary gland infection  0/112 (0.00%)  0 1/1328 (0.08%)  1
Sepsis  0/112 (0.00%)  0 6/1328 (0.45%)  6
Sinusitis  1/112 (0.89%)  1 4/1328 (0.30%)  4
Skin infection  1/112 (0.89%)  1 9/1328 (0.68%)  9
Small intestine infection  0/112 (0.00%)  0 1/1328 (0.08%)  2
Tooth infection  0/112 (0.00%)  0 1/1328 (0.08%)  2
Upper respiratory infection  2/112 (1.79%)  2 21/1328 (1.58%)  23
Urinary tract infection  1/112 (0.89%)  1 27/1328 (2.03%)  35
Wound infection  0/112 (0.00%)  0 4/1328 (0.30%)  4
Injury, poisoning and procedural complications     
Bruising  0/112 (0.00%)  0 2/1328 (0.15%)  2
Burn  0/112 (0.00%)  0 1/1328 (0.08%)  1
Fracture  0/112 (0.00%)  0 5/1328 (0.38%)  5
Injury poisoning and procedural complications - Other specify  0/112 (0.00%)  0 1/1328 (0.08%)  1
Radiation recall reaction (dermatologic)  0/112 (0.00%)  0 3/1328 (0.23%)  3
Vascular access complication  0/112 (0.00%)  0 6/1328 (0.45%)  6
Investigations     
Activated partial thromboplastin time prolonged  1/112 (0.89%)  1 6/1328 (0.45%)  6
Alanine aminotransferase increased  33/112 (29.46%)  79 281/1328 (21.16%)  560
Alkaline phosphatase increased  7/112 (6.25%)  14 35/1328 (2.64%)  53
Aspartate aminotransferase increased  6/112 (5.36%)  11 180/1328 (13.55%)  279
Blood bilirubin increased  5/112 (4.46%)  7 28/1328 (2.11%)  40
CD4 lymphocytes decreased  1/112 (0.89%)  1 1/1328 (0.08%)  1
Cholesterol high  1/112 (0.89%)  4 12/1328 (0.90%)  30
Creatinine increased  6/112 (5.36%)  12 44/1328 (3.31%)  67
Fibrinogen decreased  0/112 (0.00%)  0 1/1328 (0.08%)  1
Forced expiratory volume decreased  1/112 (0.89%)  1 0/1328 (0.00%)  0
GGT increased  0/112 (0.00%)  0 97/1328 (7.30%)  217
INR increased  0/112 (0.00%)  0 2/1328 (0.15%)  2
Investigations - Other specify  2/112 (1.79%)  4 18/1328 (1.36%)  28
Lipase increased  0/112 (0.00%)  0 4/1328 (0.30%)  4
Lymphocyte count decreased  40/112 (35.71%)  97 323/1328 (24.32%)  739
Lymphocyte count increased  0/112 (0.00%)  0 2/1328 (0.15%)  2
Neutrophil count decreased  18/112 (16.07%)  24 272/1328 (20.48%)  470
Pancreatic enzymes decreased  0/112 (0.00%)  0 1/1328 (0.08%)  1
Platelet count decreased  47/112 (41.96%)  144 356/1328 (26.81%)  876
Serum amylase increased  0/112 (0.00%)  0 5/1328 (0.38%)  12
Urine output decreased  0/112 (0.00%)  0 31/1328 (2.33%)  57
Weight gain  0/112 (0.00%)  0 50/1328 (3.77%)  90
Weight loss  0/112 (0.00%)  0 15/1328 (1.13%)  15
White blood cell decreased  16/112 (14.29%)  37 158/1328 (11.90%)  297
Metabolism and nutrition disorders     
Acidosis  0/112 (0.00%)  0 25/1328 (1.88%)  48
Alkalosis  0/112 (0.00%)  0 3/1328 (0.23%)  4
Anorexia  5/112 (4.46%)  12 100/1328 (7.53%)  189
Dehydration  2/112 (1.79%)  2 14/1328 (1.05%)  14
Glucose intolerance  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hypercalcemia  8/112 (7.14%)  17 36/1328 (2.71%)  44
Hyperglycemia  4/112 (3.57%)  5 77/1328 (5.80%)  129
Hyperkalemia  4/112 (3.57%)  4 46/1328 (3.46%)  58
Hypermagnesemia  1/112 (0.89%)  1 13/1328 (0.98%)  13
Hypernatremia  1/112 (0.89%)  1 12/1328 (0.90%)  12
Hypertriglyceridemia  11/112 (9.82%)  17 77/1328 (5.80%)  162
Hyperuricemia  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hypoalbuminemia  3/112 (2.68%)  4 156/1328 (11.75%)  359
Hypocalcemia  1/112 (0.89%)  1 128/1328 (9.64%)  229
Hypoglycemia  0/112 (0.00%)  0 29/1328 (2.18%)  35
Hypokalemia  6/112 (5.36%)  12 409/1328 (30.80%)  664
Hypomagnesemia  1/112 (0.89%)  1 40/1328 (3.01%)  55
Hyponatremia  13/112 (11.61%)  31 262/1328 (19.73%)  466
Hypophosphatemia  3/112 (2.68%)  7 114/1328 (8.58%)  141
Iron overload  1/112 (0.89%)  1 1/1328 (0.08%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  3/112 (2.68%)  7 14/1328 (1.05%)  18
Arthritis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Back pain  1/112 (0.89%)  1 69/1328 (5.20%)  97
Bone pain  2/112 (1.79%)  5 14/1328 (1.05%)  17
Buttock pain  0/112 (0.00%)  0 4/1328 (0.30%)  4
Chest wall pain  2/112 (1.79%)  2 16/1328 (1.20%)  19
Flank pain  0/112 (0.00%)  0 1/1328 (0.08%)  1
Generalized muscle weakness  1/112 (0.89%)  1 1/1328 (0.08%)  1
Muscle weakness lower limb  0/112 (0.00%)  0 2/1328 (0.15%)  2
Musculoskeletal and connective tissue disorder - Other specify  0/112 (0.00%)  0 2/1328 (0.15%)  2
Myalgia  2/112 (1.79%)  4 9/1328 (0.68%)  11
Neck pain  0/112 (0.00%)  0 26/1328 (1.96%)  36
Osteoporosis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Pain in extremity  4/112 (3.57%)  7 132/1328 (9.94%)  207
Pelvic soft tissue necrosis  0/112 (0.00%)  0 1/1328 (0.08%)  1
Nervous system disorders     
Ataxia  1/112 (0.89%)  1 1/1328 (0.08%)  1
Depressed level of consciousness  0/112 (0.00%)  0 7/1328 (0.53%)  7
Dizziness  0/112 (0.00%)  0 2/1328 (0.15%)  2
Dysgeusia  0/112 (0.00%)  0 2/1328 (0.15%)  3
Dysphasia  0/112 (0.00%)  0 1/1328 (0.08%)  1
Headache  4/112 (3.57%)  5 56/1328 (4.22%)  73
Hypoglossal nerve disorder  0/112 (0.00%)  0 1/1328 (0.08%)  1
Intracranial hemorrhage  0/112 (0.00%)  0 1/1328 (0.08%)  1
Memory impairment  0/112 (0.00%)  0 1/1328 (0.08%)  1
Movements involuntary  0/112 (0.00%)  0 1/1328 (0.08%)  1
Nervous system disorders - Other specify  1/112 (0.89%)  1 1/1328 (0.08%)  1
Neuralgia  1/112 (0.89%)  1 53/1328 (3.99%)  119
Oculomotor nerve disorder  0/112 (0.00%)  0 2/1328 (0.15%)  2
Peripheral motor neuropathy  4/112 (3.57%)  5 12/1328 (0.90%)  17
Peripheral sensory neuropathy  1/112 (0.89%)  4 19/1328 (1.43%)  27
Seizure  1/112 (0.89%)  1 9/1328 (0.68%)  9
Somnolence  0/112 (0.00%)  0 1/1328 (0.08%)  1
Stroke  0/112 (0.00%)  0 2/1328 (0.15%)  2
Syncope  1/112 (0.89%)  1 2/1328 (0.15%)  2
Vasovagal reaction  0/112 (0.00%)  0 1/1328 (0.08%)  1
Psychiatric disorders     
Agitation  2/112 (1.79%)  3 15/1328 (1.13%)  20
Anxiety  1/112 (0.89%)  1 4/1328 (0.30%)  4
Confusion  0/112 (0.00%)  0 3/1328 (0.23%)  3
Depression  0/112 (0.00%)  0 3/1328 (0.23%)  4
Euphoria  0/112 (0.00%)  0 2/1328 (0.15%)  2
Hallucinations  0/112 (0.00%)  0 2/1328 (0.15%)  2
Personality change  4/112 (3.57%)  5 3/1328 (0.23%)  3
Psychosis  0/112 (0.00%)  0 4/1328 (0.30%)  4
Renal and urinary disorders     
Acute kidney injury  1/112 (0.89%)  1 1/1328 (0.08%)  2
Bladder spasm  0/112 (0.00%)  0 1/1328 (0.08%)  1
Chronic kidney disease  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hematuria  1/112 (0.89%)  1 17/1328 (1.28%)  22
Hemoglobinuria  0/112 (0.00%)  0 2/1328 (0.15%)  2
Proteinuria  3/112 (2.68%)  6 32/1328 (2.41%)  42
Renal and urinary disorders - Other specify  1/112 (0.89%)  2 10/1328 (0.75%)  13
Renal hemorrhage  1/112 (0.89%)  1 0/1328 (0.00%)  0
Urinary frequency  2/112 (1.79%)  2 0/1328 (0.00%)  0
Urinary retention  0/112 (0.00%)  0 30/1328 (2.26%)  47
Urinary tract obstruction  0/112 (0.00%)  0 2/1328 (0.15%)  4
Urinary tract pain  0/112 (0.00%)  0 4/1328 (0.30%)  4
Urine discoloration  0/112 (0.00%)  0 2/1328 (0.15%)  4
Reproductive system and breast disorders     
Pelvic pain  0/112 (0.00%)  0 1/1328 (0.08%)  1
Penile pain  0/112 (0.00%)  0 10/1328 (0.75%)  12
Perineal pain  0/112 (0.00%)  0 1/1328 (0.08%)  1
Vaginal pain  0/112 (0.00%)  0 2/1328 (0.15%)  2
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome  1/112 (0.89%)  1 4/1328 (0.30%)  4
Allergic rhinitis  1/112 (0.89%)  4 5/1328 (0.38%)  7
Apnea  0/112 (0.00%)  0 2/1328 (0.15%)  2
Atelectasis  0/112 (0.00%)  0 5/1328 (0.38%)  5
Bronchospasm  1/112 (0.89%)  2 29/1328 (2.18%)  36
Chylothorax  0/112 (0.00%)  0 2/1328 (0.15%)  2
Cough  2/112 (1.79%)  5 84/1328 (6.33%)  115
Dyspnea  3/112 (2.68%)  3 111/1328 (8.36%)  146
Epistaxis  3/112 (2.68%)  3 5/1328 (0.38%)  5
Hypoxia  3/112 (2.68%)  3 179/1328 (13.48%)  275
Laryngeal edema  0/112 (0.00%)  0 2/1328 (0.15%)  2
Laryngeal obstruction  0/112 (0.00%)  0 1/1328 (0.08%)  1
Pharyngolaryngeal pain  0/112 (0.00%)  0 12/1328 (0.90%)  16
Pleural effusion  1/112 (0.89%)  1 4/1328 (0.30%)  4
Pneumonitis  0/112 (0.00%)  0 4/1328 (0.30%)  4
Pneumothorax  0/112 (0.00%)  0 1/1328 (0.08%)  1
Pulmonary edema  0/112 (0.00%)  0 3/1328 (0.23%)  3
Pulmonary fibrosis  0/112 (0.00%)  0 2/1328 (0.15%)  2
Respiratory thoracic and mediastinal disorders - Other specify  0/112 (0.00%)  0 10/1328 (0.75%)  10
Respiratory failure  0/112 (0.00%)  0 2/1328 (0.15%)  2
Sinus disorder  1/112 (0.89%)  1 0/1328 (0.00%)  0
Sore throat  0/112 (0.00%)  0 7/1328 (0.53%)  10
Stridor  0/112 (0.00%)  0 4/1328 (0.30%)  4
Voice alteration  0/112 (0.00%)  0 1/1328 (0.08%)  1
Wheezing  0/112 (0.00%)  0 5/1328 (0.38%)  5
Skin and subcutaneous tissue disorders     
Alopecia  0/112 (0.00%)  0 1/1328 (0.08%)  1
Dry skin  16/112 (14.29%)  29 57/1328 (4.29%)  98
Erythema multiforme  6/112 (5.36%)  7 6/1328 (0.45%)  7
Hyperhidrosis  0/112 (0.00%)  0 6/1328 (0.45%)  6
Nail loss  1/112 (0.89%)  1 0/1328 (0.00%)  0
Pain of skin  0/112 (0.00%)  0 13/1328 (0.98%)  15
Palmar-plantar erythrodysesthesia syndrome  0/112 (0.00%)  0 3/1328 (0.23%)  3
Periorbital edema  0/112 (0.00%)  0 3/1328 (0.23%)  5
Pruritus  2/112 (1.79%)  2 60/1328 (4.52%)  89
Purpura  0/112 (0.00%)  0 3/1328 (0.23%)  4
Rash acneiform  0/112 (0.00%)  0 1/1328 (0.08%)  1
Rash maculo-papular  5/112 (4.46%)  8 41/1328 (3.09%)  48
Skin and subcutaneous tissue disorders - Other specify  2/112 (1.79%)  2 22/1328 (1.66%)  35
Skin induration  0/112 (0.00%)  0 3/1328 (0.23%)  4
Skin ulceration  0/112 (0.00%)  0 1/1328 (0.08%)  1
Urticaria  6/112 (5.36%)  9 606/1328 (45.63%)  1151
Vascular disorders     
Capillary leak syndrome  2/112 (1.79%)  2 533/1328 (40.14%)  1089
Flushing  0/112 (0.00%)  0 5/1328 (0.38%)  5
Hematoma  0/112 (0.00%)  0 1/1328 (0.08%)  1
Hypertension  7/112 (6.25%)  16 48/1328 (3.61%)  67
Hypotension  6/112 (5.36%)  9 797/1328 (60.02%)  1824
Thromboembolic event  0/112 (0.00%)  0 1/1328 (0.08%)  1
Vascular disorders - Other specify  3/112 (2.68%)  5 17/1328 (1.28%)  24
1
Term from vocabulary, CTCv4
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.
Results Point of Contact
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00026312     History of Changes
Other Study ID Numbers: NCI-2009-01064
NCI-2009-01064 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000069018
COG-ANBL0032
PANBL0032_A33PAMDREVW01
ANBL0032
ANBL0032 ( Other Identifier: Childrens Oncology Group )
ANBL0032 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA030969 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted: November 9, 2001
First Posted: January 27, 2003
Results First Submitted: February 9, 2017
Results First Posted: March 29, 2017
Last Update Posted: May 10, 2017