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Trial record 63 of 170 for:    "Acute Lymphocytic Leukemia" | "Etoposide"

Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT00557193
Recruitment Status : Completed
First Posted : November 12, 2007
Results First Posted : December 10, 2018
Last Update Posted : April 9, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Acute Lymphoblastic Leukemia
Acute Undifferentiated Leukemia
Childhood T Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Interventions Drug: Asparaginase
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Daunorubicin Hydrochloride
Drug: Dexamethasone
Drug: Etoposide
Biological: Filgrastim
Other: Laboratory Biomarker Analysis
Drug: Lestaurtinib
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Methylprednisolone
Drug: Pegaspargase
Other: Pharmacological Study
Drug: Prednisone
Drug: Therapeutic Hydrocortisone
Drug: Vincristine Sulfate
Enrollment 218
Recruitment Details Infants with Acute Lymphoblastic Leukemia (ALL)
Pre-assignment Details MLL-germline [G] to SR (Arm A/Group 1), MLL-rearranged [R] randomized/assigned to Arm B (Group2; chemo) or Arm C (Group3; chemo+lestaurtinib) with dose determined by age at dx (>=90 days is IR and <90 days is HR)
Arm/Group Title Induction (All Patients) Arm A (Standard Risk MLL-G) Arm B (IR/HR MLL-R Chemotherapy) Arm C (Safety/ Dose Level 1) ARM C (Safety/ Dose Level 2) Arm C (Efficacy/ Dose Level 2)
Hide Arm/Group Description All Patients for Induction (not assigned).

Eligible patients with MLL-G (germline, or non-rearranged)

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 1 (DL1) (HR: 3.5 mg/kg/day; SR: 4 mg/kg/day) Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 2 (DL2) (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day) Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 2 (DL2)-Efficacy (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day)
Period Title: Induction
Started 218 0 0 0 0 0
Completed 192 0 0 0 0 0
Not Completed 26 0 0 0 0 0
Reason Not Completed
Adverse Event             2             0             0             0             0             0
Death             6             0             0             0             0             0
Physician Decision             3             0             0             0             0             0
Withdrawal by Subject             1             0             0             0             0             0
Refusal of Further Protocol Therapy             2             0             0             0             0             0
Ineligible             8             0             0             0             0             0
Inevaluable for post Induction             2             0             0             0             0             0
Unable to receive Lestaurtinib-Not in US             2             0             0             0             0             0
Period Title: Post Induction Therapy by Tx Assignment
Started 0 60 54 11 11 56
Completed 0 50 22 4 4 19
Not Completed 0 10 32 7 7 37
Reason Not Completed
Adverse Event             0             1             2             1             0             3
Death             0             0             2             0             2             2
Physician Decision             0             3             5             1             2             2
Refusal of Further Protocol             0             1             0             2             2             5
Relapse             0             5             16             3             1             20
Developed second malignant neoplasm             0             0             1             0             0             0
Patient Moved to Another Institution             0             0             2             0             0             0
Induction Failure             0             0             4             0             0             5
Arm/Group Title All Patients
Hide Arm/Group Description All patients for Induction
Overall Number of Baseline Participants 218
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 218 participants
<=18 years
218
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 218 participants
0.54  (0.28)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 218 participants
Female
122
  56.0%
Male
96
  44.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 218 participants
Hispanic or Latino
50
  22.9%
Not Hispanic or Latino
160
  73.4%
Unknown or Not Reported
8
   3.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 218 participants
American Indian or Alaska Native
3
   1.4%
Asian
9
   4.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
16
   7.3%
White
167
  76.6%
More than one race
0
   0.0%
Unknown or Not Reported
23
  10.6%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 218 participants
United States
201
  92.2%
Canada
15
   6.9%
New Zealand
1
   0.5%
Australia
1
   0.5%
1.Primary Outcome
Title Percent Probability for Event-free Survival (EFS) for Patients on Arm C at Dose Level 2 (DL2)
Hide Description EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto.
Time Frame From start of post-induction therapy for up to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
All 67 patients on Arm C (Safety and Efficacy at Dose Level 2) were included in the analysis.
Arm/Group Title Arm C (Safety/Efficacy Dose Level 2)
Hide Arm/Group Description:
Arm C (Safety and Efficacy), IR/HR MLL-R chemotherapy and lestaurtinib at DL2 (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day)
Overall Number of Participants Analyzed 67
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage probability
35.82
(25.98 to 45.66)
2.Secondary Outcome
Title Percent Probability for Event-free Survival (EFS) of MLL-R Infants Treated With Combination Chemotherapy With or Without Lestaurtinib at DL2
Hide Description Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto. EFS will be compared between patients on treatment Arm C at DL2 to those on Arm B.
Time Frame From start of post-induction therapy for up to 10 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible Arm B and ARM C (Dose Level 2) patients were included in the analysis.
Arm/Group Title Arm B (IR/HR MLL-R Chemotherapy) Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib)
Hide Arm/Group Description:

Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Lestaurtinib: Given PO

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 54 67
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percent probability
38.89
(27.98 to 49.80)
35.82
(25.98 to 45.66)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm B (IR/HR MLL-R Chemotherapy), Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib)
Comments A one-sided log rank test will be used for testing whether the EFS in Arm C (chemo+lest) at DL2 is greater than the EFS in Arm B (chemo). This is equivalent to testing the null hypothesis of hazard ratio (HR)=1 versus the alternative of HR<1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.672
Comments A priori significance level threshold of alpha=0.15
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.107
Confidence Interval (1-Sided) 85%
1.403
Estimation Comments Arm C is the numerator and Arm B is the denominator of the estimated hazard ratio
3.Secondary Outcome
Title Number of Patients Who Experienced Lestaurtinib-related Dose Limiting Toxicity (DLT)
Hide Description Lestaurtinib-related dose-limiting toxicity proportions, as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, will by summarized by dose level for Safety phase patients.
Time Frame Up to 12 weeks from start of induction
Hide Outcome Measure Data
Hide Analysis Population Description
Arm C patients of Safety Phase who were evaluable for DLT. The first 10 evaluable patients enrolled on each dose level were included for monitoring dose limiting toxicity.
Arm/Group Title Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib-Dose Level 1) Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib-Dose Level 2)
Hide Arm/Group Description:
Evaluable Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at DL1 (HR: 3.5 mg/kg/day; SR: 4 mg/kg/day)
Evaluable Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at DL2 (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day)
Overall Number of Participants Analyzed 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
  10.0%
4.Secondary Outcome
Title Pharmacokinetic AGP Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy
Hide Description Pharmacokinetic AGP levels in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data.
Time Frame Up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Data was and never will be collected
Arm/Group Title Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib)
Hide Arm/Group Description:

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Lestaurtinib: Given PO

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Pharmacokinetic Albumin in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy
Hide Description Pharmacokinetic albumin in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data.
Time Frame Up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Data was and never will be collected
Arm/Group Title Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib)
Hide Arm/Group Description:

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Lestaurtinib: Given PO

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Pharmacodynamics PIA Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy
Hide Description Summarized with mean and standard deviation for those with available data in Arm C
Time Frame Sampled between weeks 6-12 from start of induction
Hide Outcome Measure Data
Hide Analysis Population Description
Arm C Dose Level 2 (DL2) patients who had data available for analysis.
Arm/Group Title Arm C (Safety/Efficacy Dose Level 2)
Hide Arm/Group Description:
Arm C (Safety and Efficacy), IR/HR MLL-R chemotherapy and lestaurtinib at DL2 (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day)
Overall Number of Participants Analyzed 63
Mean (Standard Deviation)
Unit of Measure: Activity percentage
69.00  (22.96)
7.Secondary Outcome
Title Describe FLT3 Protein Expression as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts
Hide Description Described via mean and standard deviation by group.
Time Frame Sampled at the start of induction
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who had data collected
Arm/Group Title Arm A (Standard Risk MLL-G) Arm B (IR/HR MLL-R Chemotherapy) Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib)
Hide Arm/Group Description:

Population Description: Eligible patients with MLL-G (germline, or non-rearranged)

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Lestaurtinib: Given PO

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 51 38 65
Mean (Standard Deviation)
Unit of Measure: qPCR fold expression ratio
1.25  (2.12) 7.85  (10.65) 5.83  (5.55)
8.Secondary Outcome
Title Describe FLT3 Protein Expression as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts
Hide Description Described via means and standard deviations in available Arm C relapse samples
Time Frame At relapse (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Arm C Dose Level 2 patients who relapsed and had data collected.
Arm/Group Title Arm C (Safety/Efficacy Dose Level 2)
Hide Arm/Group Description:
Arm C (Safety and Efficacy), IR/HR MLL-R chemotherapy and lestaurtinib at DL2 (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day)
Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: qPCR fold expression ratio
5.73  (4.56)
9.Secondary Outcome
Title Describe in Vitro Sensitivity as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts
Hide Description Described via means and standard deviations in samples which have primary resistance to lestaurtinib
Time Frame Sampled at the start of induction
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who had data collected
Arm/Group Title Arm A (Standard Risk MLL-G) Arm B (IR/HR MLL-R Chemotherapy) Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib)
Hide Arm/Group Description:

Population Description: Eligible patients with MLL-G (germline, or non-rearranged)

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Lestaurtinib: Given PO

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 43 37 62
Median (Standard Deviation)
Unit of Measure: Proportion of cells that are viable
0.75  (0.14) 0.48  (0.19) 0.47  (0.19)
10.Secondary Outcome
Title Describe in Vitro Sensitivity as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts
Hide Description Described via means and standard deviations in samples which have acquired resistance to lestaurtinib
Time Frame At relapse (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Arm C Dose Level 2 patients who relapsed and had data collected
Arm/Group Title Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib)
Hide Arm/Group Description:

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Lestaurtinib: Given PO

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: Proportion of cells that are viable
0.69  (0.15)
11.Secondary Outcome
Title Percent Probability of Event Free Survival (EFS) by MRD Status and Treatment Arm
Hide Description Three-year EFS estimates and 90% CI will be reported by treatment arm and end-induction MRD status.
Time Frame 3 Years from end of Induction)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who had data collected
Arm/Group Title Arm A (MRD Negative) Arm A (MRD Positive) Arm B (MRD Negative) Arm B (MRD Positive) Arm C (MRD Negative) Arm C (MRD Positive)
Hide Arm/Group Description:
Arm A, standard risk MLL-G
Arm A, standard risk MLL-G
Arm B, IR/HR MLL-R chemotherapy
Arm B, IR/HR MLL-R chemotherapy
Arm C, IR/HR MLL-R chemotherapy and lestaurtinib
Arm C, IR/HR MLL-R chemotherapy and lestaurtinib
Overall Number of Participants Analyzed 43 8 19 22 27 37
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percent probability
86.05
(77.36 to 94.74)
87.5
(68.27 to 100)
47.37
(28.53 to 66.21)
22.73
(8.04 to 37.42)
51.85
(36.03 to 67.67)
27.03
(13.61 to 40.45)
12.Secondary Outcome
Title Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With Survival Outcomes
Hide Description EFS outcomes will be reported by genotype.
Time Frame At 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Data was and never will never be collected.
Arm/Group Title Arm A (Standard Risk MLL-G) Arm B (IR/HR MLL-R Chemotherapy) Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib)
Hide Arm/Group Description:

Population Description: Eligible patients with MLL-G (germline, or non-rearranged)

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Lestaurtinib: Given PO

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With PIA Values
Hide Description Means and standard deviations of Plasma Inhibitory Activity (PIA) will be given by genotype
Time Frame At 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Data was and never will be collected
Arm/Group Title Arm A (Standard Risk MLL-G) Arm B (IR/HR MLL-R Chemotherapy) Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib)
Hide Arm/Group Description:

Population Description: Eligible patients with MLL-G (germline, or non-rearranged)

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Lestaurtinib: Given PO

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title Percent Probability for Event-free Survival (EFS) for Patients on Arm A
Hide Description EFS time is defined as time from treatment assignment to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto.
Time Frame From start of post-induction therapy for up to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
All Eligible patients treated in Arm A (standard risk MLL-G).
Arm/Group Title Arm A (Standard Risk MLL-G)
Hide Arm/Group Description:

Eligible patients with MLL-G (germline, or non-rearranged)

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 60
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage probability
86.67
(79.45 to 93.89)
Time Frame Group 1: Study Entry to end-Induction (5 weeks). Other Groups: Start of Induction Intensification (Week 6) through 10 years post study enrollment.
Adverse Event Reporting Description Adverse event reporting is collected routinely using case report forms. SAE field contains NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients are excluded from reporting of adverse events.
 
Arm/Group Title Induction (All Patients) Post Induction (Follow-up Only) Arm A (Standard Risk MLL-G) Arm B (IR/HR MLL-R Chemotherapy) Arm C (Safety/ Dose Level 1) Arm C (Safety/ Dose Level 2) Arm C (Efficacy/ Dose Level 2)
Hide Arm/Group Description All Patients for Induction (not assigned) Post-Induction patients that did not receive therapy

Population Description: Eligible patients with MLL-G (germline, or non-rearranged)

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Asparaginase: Given IV, IM, or PO

Cyclophosphamide: Given IV

Cytarabine: Given IV or IT

Daunorubicin Hydrochloride: Given IV

Dexamethasone: Given IV or PO

Etoposide: Given IV

Filgrastim: Given IV or SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IV, IT, or PO

Methylprednisolone: Given IV

Pegaspargase: Given IM

Pharmacological Study: Correlative studies

Prednisone: Given PO

Therapeutic Hydrocortisone: Given IT

Vincristine Sulfate: Given IV

Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 1 (DL1) (HR: 3.5 mg/kg/day; SR: 4 mg/kg/day) Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 2 (DL2) (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day) Arm C, IR/HR MLL-R chemotherapy and lestaurtinib at Dose Level 2 (DL2)-Efficacy (HR: 4.25 mg/kg/day; SR: 5 mg/kg/day)
All-Cause Mortality
Induction (All Patients) Post Induction (Follow-up Only) Arm A (Standard Risk MLL-G) Arm B (IR/HR MLL-R Chemotherapy) Arm C (Safety/ Dose Level 1) Arm C (Safety/ Dose Level 2) Arm C (Efficacy/ Dose Level 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/210 (2.86%)      6/12 (50.00%)      3/60 (5.00%)      31/54 (57.41%)      6/11 (54.55%)      5/11 (45.45%)      28/56 (50.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Induction (All Patients) Post Induction (Follow-up Only) Arm A (Standard Risk MLL-G) Arm B (IR/HR MLL-R Chemotherapy) Arm C (Safety/ Dose Level 1) Arm C (Safety/ Dose Level 2) Arm C (Efficacy/ Dose Level 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/210 (4.29%)      0/12 (0.00%)      2/60 (3.33%)      9/54 (16.67%)      8/11 (72.73%)      7/11 (63.64%)      41/56 (73.21%)    
Blood and lymphatic system disorders               
Anemia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 1/11 (9.09%)  1 2/56 (3.57%)  5
Blood and lymphatic system disorders - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Febrile neutropenia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 6/11 (54.55%)  7 1/11 (9.09%)  1 22/56 (39.29%)  42
Hemolytic uremic syndrome  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Thrombotic thrombocytopenic purpura  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 0/56 (0.00%)  0
Cardiac disorders               
Cardiac arrest  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 1/56 (1.79%)  1
Heart failure  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Left ventricular systolic dysfunction  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 2/56 (3.57%)  2
Myocarditis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Sinus tachycardia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 2/56 (3.57%)  3
Gastrointestinal disorders               
Ascites  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 1/11 (9.09%)  1 1/56 (1.79%)  1
Colitis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 2/11 (18.18%)  2 0/11 (0.00%)  0 3/56 (5.36%)  6
Diarrhea  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 5/11 (45.45%)  9 3/11 (27.27%)  3 11/56 (19.64%)  14
Enterocolitis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  2
Gastric hemorrhage  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Gastrointestinal disorders - Other, specify  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 5/56 (8.93%)  5
Gastrointestinal fistula  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
Lower gastrointestinal hemorrhage  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 2/56 (3.57%)  2
Mucositis oral  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 1/11 (9.09%)  1 2/11 (18.18%)  3 9/56 (16.07%)  11
Oral pain  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Small intestinal perforation  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
Typhlitis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
Vomiting  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 2/56 (3.57%)  2
General disorders               
Death NOS  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 3/56 (5.36%)  3
Fatigue  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 0/56 (0.00%)  0
Fever  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 2/11 (18.18%)  2 3/56 (5.36%)  4
General disorders and administration site conditions - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
Irritability  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Multi-organ failure  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Immune system disorders               
Anaphylaxis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Immune system disorders - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Infections and infestations               
Abdominal infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 0/56 (0.00%)  0
Anorectal infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 1/56 (1.79%)  1
Bronchial infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Catheter related infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 2/11 (18.18%)  3 2/11 (18.18%)  3 6/56 (10.71%)  6
Endocarditis infective  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Enterocolitis infectious  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 3/56 (5.36%)  3
Hepatic infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Infections and infestations - Other, specify  1  5/210 (2.38%)  6 0/12 (0.00%)  0 0/60 (0.00%)  0 2/54 (3.70%)  2 6/11 (54.55%)  22 5/11 (45.45%)  9 23/56 (41.07%)  43
Lung infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 2/54 (3.70%)  3 3/11 (27.27%)  4 1/11 (9.09%)  1 1/56 (1.79%)  1
Mucosal infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Peritoneal infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
Sepsis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 2/54 (3.70%)  2 1/11 (9.09%)  1 1/11 (9.09%)  1 11/56 (19.64%)  14
Skin infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 3/56 (5.36%)  3
Small intestine infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 2/56 (3.57%)  2
Soft tissue infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 2/56 (3.57%)  2
Tracheitis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
Upper respiratory infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 0/56 (0.00%)  0
Urinary tract infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 2/11 (18.18%)  2 3/56 (5.36%)  3
Wound infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 1/11 (9.09%)  1 0/56 (0.00%)  0
Injury, poisoning and procedural complications               
Injury, poisoning and procedural complications - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 2/56 (3.57%)  2
Vascular access complication  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Investigations               
Activated partial thromboplastin time prolonged  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Alanine aminotransferase increased  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 3/11 (27.27%)  12 1/11 (9.09%)  4 10/56 (17.86%)  16
Aspartate aminotransferase increased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 1/11 (9.09%)  2 1/11 (9.09%)  4 8/56 (14.29%)  9
Blood bilirubin increased  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 1/11 (9.09%)  1 2/56 (3.57%)  2
Creatinine increased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Fibrinogen decreased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
GGT increased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 1/56 (1.79%)  1
Investigations - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Lipase increased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
Lymphocyte count decreased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 1/11 (9.09%)  2 1/56 (1.79%)  2
Neutrophil count decreased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 1/11 (9.09%)  2 2/11 (18.18%)  3 7/56 (12.50%)  10
Platelet count decreased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 2/11 (18.18%)  3 3/56 (5.36%)  6
Weight loss  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 2/11 (18.18%)  2 0/11 (0.00%)  0 0/56 (0.00%)  0
White blood cell decreased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 1/11 (9.09%)  2 2/11 (18.18%)  3 2/56 (3.57%)  5
Metabolism and nutrition disorders               
Acidosis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Anorexia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 2/11 (18.18%)  2 1/11 (9.09%)  1 1/56 (1.79%)  1
Dehydration  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 2/11 (18.18%)  3 2/11 (18.18%)  2 6/56 (10.71%)  9
Hyperglycemia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 0/56 (0.00%)  0
Hypernatremia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 2/11 (18.18%)  2 1/56 (1.79%)  1
Hypertriglyceridemia  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Hypoalbuminemia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 5/56 (8.93%)  6
Hypocalcemia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Hypoglycemia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 3/56 (5.36%)  4
Hypokalemia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 2/11 (18.18%)  3 1/11 (9.09%)  1 6/56 (10.71%)  6
Hyponatremia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Hypophosphatemia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 1/56 (1.79%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Treatment related secondary malignancy  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Nervous system disorders               
Abducens nerve disorder  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 0/56 (0.00%)  0
Cognitive disturbance  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 2/56 (3.57%)  2
Depressed level of consciousness  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  2 0/11 (0.00%)  0 0/56 (0.00%)  0
Encephalopathy  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 1/11 (9.09%)  1 1/56 (1.79%)  1
Oculomotor nerve disorder  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Seizure  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 2/11 (18.18%)  2 1/11 (9.09%)  1 2/56 (3.57%)  2
Stroke  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Psychiatric disorders               
Psychiatric disorders - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Renal and urinary disorders               
Acute kidney injury  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 2/56 (3.57%)  2
Respiratory, thoracic and mediastinal disorders               
Adult respiratory distress syndrome  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Apnea  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 0/56 (0.00%)  0
Aspiration  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Atelectasis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Dyspnea  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Hypoxia  1  2/210 (0.95%)  2 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 1/11 (9.09%)  1 2/11 (18.18%)  2 4/56 (7.14%)  4
Pneumonitis  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  2 0/56 (0.00%)  0
Respiratory failure  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 1/11 (9.09%)  1 0/11 (0.00%)  0 4/56 (7.14%)  5
Skin and subcutaneous tissue disorders               
Rash maculo-papular  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 2/11 (18.18%)  2 0/11 (0.00%)  0 0/56 (0.00%)  0
Skin and subcutaneous tissue disorders - Other, specify  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 2/56 (3.57%)  3
Skin ulceration  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 3/56 (5.36%)  3
Surgical and medical procedures               
Surgical and medical procedures - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
Vascular disorders               
Hypertension  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 1/56 (1.79%)  1
Hypotension  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 2/11 (18.18%)  2 1/11 (9.09%)  1 5/56 (8.93%)  5
Thromboembolic event  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Visceral arterial ischemia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
1
Term from vocabulary, CTCv4
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Induction (All Patients) Post Induction (Follow-up Only) Arm A (Standard Risk MLL-G) Arm B (IR/HR MLL-R Chemotherapy) Arm C (Safety/ Dose Level 1) Arm C (Safety/ Dose Level 2) Arm C (Efficacy/ Dose Level 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   181/210 (86.19%)      5/12 (41.67%)      59/60 (98.33%)      54/54 (100.00%)      11/11 (100.00%)      11/11 (100.00%)      55/56 (98.21%)    
Blood and lymphatic system disorders               
Anemia  1  4/210 (1.90%)  4 0/12 (0.00%)  0 4/60 (6.67%)  7 4/54 (7.41%)  7 1/11 (9.09%)  2 1/11 (9.09%)  1 5/56 (8.93%)  7
Blood and lymphatic system disorders - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Disseminated intravascular coagulation  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Febrile neutropenia  1  31/210 (14.76%)  32 0/12 (0.00%)  0 34/60 (56.67%)  58 32/54 (59.26%)  69 6/11 (54.55%)  9 4/11 (36.36%)  13 26/56 (46.43%)  40
Leukocytosis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Cardiac disorders               
Cardiac arrest  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Cardiac disorders - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Myocarditis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Sinus tachycardia  1  2/210 (0.95%)  2 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 3/56 (5.36%)  3
Eye disorders               
Blurred vision  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Eye disorders - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Gastrointestinal disorders               
Abdominal distension  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Abdominal pain  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 2/11 (18.18%)  2 1/11 (9.09%)  1 0/56 (0.00%)  0
Anal mucositis  1  3/210 (1.43%)  3 0/12 (0.00%)  0 1/60 (1.67%)  1 2/54 (3.70%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0 2/56 (3.57%)  2
Anal pain  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 0/56 (0.00%)  0
Colitis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 3/54 (5.56%)  3 1/11 (9.09%)  1 1/11 (9.09%)  1 0/56 (0.00%)  0
Diarrhea  1  15/210 (7.14%)  16 0/12 (0.00%)  0 15/60 (25.00%)  21 14/54 (25.93%)  24 2/11 (18.18%)  5 1/11 (9.09%)  1 16/56 (28.57%)  28
Dysphagia  1  3/210 (1.43%)  3 0/12 (0.00%)  0 0/60 (0.00%)  0 2/54 (3.70%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Enterocolitis  1  2/210 (0.95%)  2 0/12 (0.00%)  0 1/60 (1.67%)  1 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Esophagitis  1  1/210 (0.48%)  1 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Gastric hemorrhage  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Gastritis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Gastrointestinal disorders - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 3/54 (5.56%)  3 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Mucositis oral  1  13/210 (6.19%)  14 0/12 (0.00%)  0 35/60 (58.33%)  46 24/54 (44.44%)  29 6/11 (54.55%)  9 5/11 (45.45%)  10 24/56 (42.86%)  30
Nausea  1  1/210 (0.48%)  1 0/12 (0.00%)  0 1/60 (1.67%)  1 2/54 (3.70%)  2 3/11 (27.27%)  3 0/11 (0.00%)  0 1/56 (1.79%)  1
Oral hemorrhage  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Oral pain  1  2/210 (0.95%)  2 0/12 (0.00%)  0 2/60 (3.33%)  2 4/54 (7.41%)  4 1/11 (9.09%)  1 0/11 (0.00%)  0 1/56 (1.79%)  1
Rectal mucositis  1  3/210 (1.43%)  3 0/12 (0.00%)  0 0/60 (0.00%)  0 2/54 (3.70%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Small intestinal mucositis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Vomiting  1  4/210 (1.90%)  4 0/12 (0.00%)  0 2/60 (3.33%)  3 6/54 (11.11%)  6 0/11 (0.00%)  0 0/11 (0.00%)  0 4/56 (7.14%)  4
General disorders               
Death NOS  1  0/210 (0.00%)  0 3/12 (25.00%)  3 0/60 (0.00%)  0 10/54 (18.52%)  10 3/11 (27.27%)  3 1/11 (9.09%)  1 3/56 (5.36%)  3
Edema face  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Fatigue  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Fever  1  2/210 (0.95%)  3 0/12 (0.00%)  0 9/60 (15.00%)  12 6/54 (11.11%)  7 2/11 (18.18%)  2 2/11 (18.18%)  3 2/56 (3.57%)  2
General disorders and administration site conditions - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 2/54 (3.70%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Hypothermia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Infusion related reaction  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Irritability  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 2/54 (3.70%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  2
Multi-organ failure  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Pain  1  3/210 (1.43%)  3 0/12 (0.00%)  0 2/60 (3.33%)  2 2/54 (3.70%)  3 1/11 (9.09%)  1 0/11 (0.00%)  0 3/56 (5.36%)  3
Hepatobiliary disorders               
Hepatic failure  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Immune system disorders               
Allergic reaction  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Anaphylaxis  1  1/210 (0.48%)  1 0/12 (0.00%)  0 2/60 (3.33%)  2 2/54 (3.70%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Immune system disorders - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 2/54 (3.70%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Infections and infestations               
Anorectal infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 3/54 (5.56%)  3 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Bladder infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 1/54 (1.85%)  1 0/11 (0.00%)  0 1/11 (9.09%)  1 1/56 (1.79%)  2
Bronchial infection  1  2/210 (0.95%)  3 0/12 (0.00%)  0 3/60 (5.00%)  3 1/54 (1.85%)  1 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
Catheter related infection  1  5/210 (2.38%)  6 0/12 (0.00%)  0 13/60 (21.67%)  20 12/54 (22.22%)  21 3/11 (27.27%)  4 1/11 (9.09%)  3 8/56 (14.29%)  10
Endocarditis infective  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  3
Enterocolitis infectious  1  4/210 (1.90%)  4 0/12 (0.00%)  0 3/60 (5.00%)  3 7/54 (12.96%)  8 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Infections and infestations - Other, specify  1  52/210 (24.76%)  66 0/12 (0.00%)  0 32/60 (53.33%)  66 36/54 (66.67%)  116 4/11 (36.36%)  18 8/11 (72.73%)  11 19/56 (33.93%)  39
Lung infection  1  4/210 (1.90%)  4 0/12 (0.00%)  0 5/60 (8.33%)  5 7/54 (12.96%)  11 1/11 (9.09%)  1 1/11 (9.09%)  1 5/56 (8.93%)  6
Meningitis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Mucosal infection  1  2/210 (0.95%)  2 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Otitis media  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 3/54 (5.56%)  3 0/11 (0.00%)  0 1/11 (9.09%)  2 4/56 (7.14%)  5
Paronychia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 0/56 (0.00%)  0
Penile infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 2/60 (3.33%)  2 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Pharyngitis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Rash pustular  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  2 0/56 (0.00%)  0
Scrotal infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  2 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Sepsis  1  7/210 (3.33%)  7 0/12 (0.00%)  0 2/60 (3.33%)  2 10/54 (18.52%)  15 1/11 (9.09%)  1 0/11 (0.00%)  0 5/56 (8.93%)  7
Sinusitis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 3/54 (5.56%)  3 2/11 (18.18%)  2 0/11 (0.00%)  0 0/56 (0.00%)  0
Skin infection  1  3/210 (1.43%)  3 0/12 (0.00%)  0 7/60 (11.67%)  8 7/54 (12.96%)  9 2/11 (18.18%)  2 3/11 (27.27%)  4 1/56 (1.79%)  2
Small intestine infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Soft tissue infection  1  1/210 (0.48%)  1 0/12 (0.00%)  0 3/60 (5.00%)  4 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Upper respiratory infection  1  6/210 (2.86%)  6 0/12 (0.00%)  0 7/60 (11.67%)  9 10/54 (18.52%)  15 0/11 (0.00%)  0 1/11 (9.09%)  1 6/56 (10.71%)  6
Urinary tract infection  1  6/210 (2.86%)  6 0/12 (0.00%)  0 7/60 (11.67%)  9 21/54 (38.89%)  30 1/11 (9.09%)  2 3/11 (27.27%)  4 13/56 (23.21%)  14
Vulval infection  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Wound infection  1  1/210 (0.48%)  1 0/12 (0.00%)  0 1/60 (1.67%)  1 1/54 (1.85%)  1 1/11 (9.09%)  1 0/11 (0.00%)  0 1/56 (1.79%)  1
Injury, poisoning and procedural complications               
Fracture  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Intraoperative hemorrhage  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Vascular access complication  1  5/210 (2.38%)  5 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Wound complication  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Investigations               
Activated partial thromboplastin time prolonged  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
Alanine aminotransferase increased  1  24/210 (11.43%)  24 0/12 (0.00%)  0 42/60 (70.00%)  94 35/54 (64.81%)  84 8/11 (72.73%)  32 7/11 (63.64%)  12 30/56 (53.57%)  57
Alkaline phosphatase increased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 4/60 (6.67%)  4 0/54 (0.00%)  0 1/11 (9.09%)  1 1/11 (9.09%)  1 1/56 (1.79%)  2
Aspartate aminotransferase increased  1  15/210 (7.14%)  15 0/12 (0.00%)  0 34/60 (56.67%)  52 28/54 (51.85%)  59 5/11 (45.45%)  11 4/11 (36.36%)  5 21/56 (37.50%)  31
Blood bilirubin increased  1  2/210 (0.95%)  3 0/12 (0.00%)  0 0/60 (0.00%)  0 4/54 (7.41%)  4 2/11 (18.18%)  3 0/11 (0.00%)  0 2/56 (3.57%)  2
Creatinine increased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
GGT increased  1  3/210 (1.43%)  3 0/12 (0.00%)  0 3/60 (5.00%)  7 3/54 (5.56%)  4 2/11 (18.18%)  7 0/11 (0.00%)  0 3/56 (5.36%)  7
Investigations - Other, specify  1  3/210 (1.43%)  3 0/12 (0.00%)  0 1/60 (1.67%)  1 1/54 (1.85%)  4 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Lipase increased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Lymphocyte count decreased  1  2/210 (0.95%)  2 0/12 (0.00%)  0 3/60 (5.00%)  3 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Neutrophil count decreased  1  74/210 (35.24%)  76 0/12 (0.00%)  0 29/60 (48.33%)  62 26/54 (48.15%)  45 9/11 (81.82%)  15 5/11 (45.45%)  8 26/56 (46.43%)  48
Platelet count decreased  1  9/210 (4.29%)  9 0/12 (0.00%)  0 9/60 (15.00%)  13 16/54 (29.63%)  24 4/11 (36.36%)  8 3/11 (27.27%)  5 12/56 (21.43%)  18
Urine output decreased  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  2
Weight gain  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0 0/56 (0.00%)  0
Weight loss  1  3/210 (1.43%)  3 0/12 (0.00%)  0 4/60 (6.67%)  9 7/54 (12.96%)  12 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
White blood cell decreased  1  6/210 (2.86%)  6 0/12 (0.00%)  0 14/60 (23.33%)  19 9/54 (16.67%)  13 2/11 (18.18%)  5 1/11 (9.09%)  1 8/56 (14.29%)  16
Metabolism and nutrition disorders               
Acidosis  1  4/210 (1.90%)  4 0/12 (0.00%)  0 1/60 (1.67%)  1 2/54 (3.70%)  3 1/11 (9.09%)  2 0/11 (0.00%)  0 0/56 (0.00%)  0
Anorexia  1  18/210 (8.57%)  18 0/12 (0.00%)  0 13/60 (21.67%)  28 15/54 (27.78%)  31 2/11 (18.18%)  2 2/11 (18.18%)  5 9/56 (16.07%)  29
Dehydration  1  4/210 (1.90%)  4 0/12 (0.00%)  0 8/60 (13.33%)  10 9/54 (16.67%)  16 1/11 (9.09%)  1 0/11 (0.00%)  0 5/56 (8.93%)  5
Hypercalcemia  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Hyperglycemia  1  19/210 (9.05%)  19 0/12 (0.00%)  0 4/60 (6.67%)  5 9/54 (16.67%)  17 3/11 (27.27%)  3 2/11 (18.18%)  2 7/56 (12.50%)  8
Hyperkalemia  1  6/210 (2.86%)  6 0/12 (0.00%)  0 1/60 (1.67%)  1 3/54 (5.56%)  4 2/11 (18.18%)  2 0/11 (0.00%)  0 2/56 (3.57%)  2
Hypernatremia  1  3/210 (1.43%)  3 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 1/11 (9.09%)  1 0/11 (0.00%)  0 2/56 (3.57%)  2
Hypertriglyceridemia  1  3/210 (1.43%)  3 0/12 (0.00%)  0 1/60 (1.67%)  1 2/54 (3.70%)  2 1/11 (9.09%)  1 0/11 (0.00%)  0 2/56 (3.57%)  2
Hypoalbuminemia  1  15/210 (7.14%)  15 0/12 (0.00%)  0 3/60 (5.00%)  3 5/54 (9.26%)  6 1/11 (9.09%)  1 0/11 (0.00%)  0 5/56 (8.93%)  6
Hypocalcemia  1  29/210 (13.81%)  29 0/12 (0.00%)  0 5/60 (8.33%)  6 3/54 (5.56%)  5 0/11 (0.00%)  0 3/11 (27.27%)  3 5/56 (8.93%)  6
Hypoglycemia  1  5/210 (2.38%)  5 0/12 (0.00%)  0 4/60 (6.67%)  6 2/54 (3.70%)  2 3/11 (27.27%)  5 0/11 (0.00%)  0 7/56 (12.50%)  8
Hypokalemia  1  35/210 (16.67%)  36 0/12 (0.00%)  0 20/60 (33.33%)  37 14/54 (25.93%)  41 6/11 (54.55%)  16 3/11 (27.27%)  4 22/56 (39.29%)  37
Hypomagnesemia  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 2/56 (3.57%)  3
Hyponatremia  1  14/210 (6.67%)  14 0/12 (0.00%)  0 5/60 (8.33%)  8 8/54 (14.81%)  9 2/11 (18.18%)  3 1/11 (9.09%)  1 2/56 (3.57%)  3
Hypophosphatemia  1  5/210 (2.38%)  5 0/12 (0.00%)  0 2/60 (3.33%)  3 2/54 (3.70%)  2 3/11 (27.27%)  4 0/11 (0.00%)  0 3/56 (5.36%)  3
Metabolism and nutrition disorders - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 2/56 (3.57%)  2
Musculoskeletal and connective tissue disorders               
Generalized muscle weakness  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Muscle weakness trunk  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Pain in extremity  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1 0/56 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Leukemia secondary to oncology chemotherapy  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 2/56 (3.57%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 4/54 (7.41%)  4 1/11 (9.09%)  1 1/11 (9.09%)  1 1/56 (1.79%)  1
Nervous system disorders               
Encephalopathy  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Intracranial hemorrhage  1  0/210 (0.00%)  0 1/12 (8.33%)  1 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Nervous system disorders - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Peripheral motor neuropathy  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  3 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Peripheral sensory neuropathy  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  3
Psychiatric disorders               
Insomnia  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Renal and urinary disorders               
Acute kidney injury  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Hematuria  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 1/11 (9.09%)  1 0/11 (0.00%)  0 0/56 (0.00%)  0
Renal and urinary disorders - Other, specify  1  1/210 (0.48%)  1 0/12 (0.00%)  0 1/60 (1.67%)  1 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Reproductive system and breast disorders               
Penile pain  1  1/210 (0.48%)  1 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Adult respiratory distress syndrome  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Atelectasis  1  1/210 (0.48%)  1 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Bronchopulmonary hemorrhage  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Cough  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Dyspnea  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Epistaxis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  2 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Hypoxia  1  6/210 (2.86%)  6 0/12 (0.00%)  0 4/60 (6.67%)  8 3/54 (5.56%)  5 0/11 (0.00%)  0 1/11 (9.09%)  1 4/56 (7.14%)  4
Laryngeal mucositis  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Pharyngeal mucositis  1  1/210 (0.48%)  1 0/12 (0.00%)  0 1/60 (1.67%)  1 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Pleural effusion  1  1/210 (0.48%)  1 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Pneumonitis  1  1/210 (0.48%)  1 0/12 (0.00%)  0 1/60 (1.67%)  1 1/54 (1.85%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Pneumothorax  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 1/54 (1.85%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Pulmonary edema  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Respiratory failure  1  1/210 (0.48%)  1 1/12 (8.33%)  1 1/60 (1.67%)  1 3/54 (5.56%)  3 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Respiratory, thoracic and mediastinal disorders - Other, specify  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 4/54 (7.41%)  7 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Sinus disorder  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Stridor  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  2 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 1/56 (1.79%)  1
Skin and subcutaneous tissue disorders               
Dry skin  1  0/210 (0.00%)  0 0/12 (0.00%)  0 1/60 (1.67%)  1 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Erythema multiforme  1  0/210 (0.00%)  0 0/12 (0.00%)  0 2/60 (3.33%)  2 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Pain of skin  1  2/210 (0.95%)  2 0/12 (0.00%)  0 2/60 (3.33%)  2 0/54 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0 0/56 (0.00%)  0
Periorbital edema  1  0/210 (0.00%)  0 0/12 (0.00%)  0 0/60 (0.00%)  0