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A Study to Evaluate 5 μg/kg Tbo-filgrastim in Infants, Children and Adolescents With Solid Tumors Without Bone Marrow Involvement

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ClinicalTrials.gov Identifier: NCT02190721
Recruitment Status : Completed
First Posted : July 15, 2014
Results First Posted : July 31, 2018
Last Update Posted : July 31, 2018
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Pharmaceutical Industries, Ltd. )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neutropenia
Intervention Drug: tbo-filgrastim
Enrollment 50
Recruitment Details A total of 55 patients were screened for this study. Of the 55 patients screened, 50 patients at 33 investigational centers in Central and Eastern Europe met inclusion/exclusion criteria and were considered to be eligible for enrollment into the study.
Pre-assignment Details Of the 5 patients who were not enrolled, 2 patients were excluded due to inclusion criteria not met (baseline AST elevation, baseline ANC count was too low), 2 patients were excluded due to exclusion criteria not met (ongoing active infection or history of infectious disease within 2 weeks prior to screening), and 1 patient withdrew consent.
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle. Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle. Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Period Title: Overall Study
Started 2 30 18
Completed Treatment 2 30 18
Completed 30 Day Follow-up 2 29 18
Completed 90 Day Follow-up 2 29 18
Completed 2 29 18
Not Completed 0 1 0
Reason Not Completed
Patient was out of the city             0             1             0
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years) Total
Hide Arm/Group Description Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle. Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle. Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle. Total of all reporting groups
Overall Number of Baseline Participants 2 30 18 50
Hide Baseline Analysis Population Description
Safety population
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 2 participants 30 participants 18 participants 50 participants
1.65
(1.4 to 1.9)
6.80
(2.4 to 11.5)
13.80
(12.0 to 15.9)
9.05
(1.4 to 15.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 30 participants 18 participants 50 participants
Female
1
  50.0%
13
  43.3%
6
  33.3%
20
  40.0%
Male
1
  50.0%
17
  56.7%
12
  66.7%
30
  60.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 30 participants 18 participants 50 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
2
 100.0%
30
 100.0%
18
 100.0%
50
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 30 participants 18 participants 50 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
2
 100.0%
30
 100.0%
18
 100.0%
50
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Weight  
Median (Full Range)
Unit of measure:  Kg
Number Analyzed 2 participants 30 participants 18 participants 50 participants
9.90
(9.3 to 10.5)
20.25
(12.0 to 51.1)
53.90
(29.5 to 89.5)
28.95
(9.3 to 89.5)
Height  
Median (Full Range)
Unit of measure:  Cm
Number Analyzed 2 participants 30 participants 18 participants 50 participants
78.00
(76.0 to 80.0)
121.00
(89.0 to 163.0)
161.00
(140.0 to 185.0)
130.50
(76.0 to 185.0)
Body Mass Index  
Median (Full Range)
Unit of measure:  Kg/m^2
Number Analyzed 2 participants 30 participants 18 participants 50 participants
16.0
(16 to 16)
15.2
(12 to 20)
20.7
(15 to 28)
16.4
(12 to 28)
Chemotherapy Administration   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 30 participants 18 participants 50 participants
Mild
0
   0.0%
6
  20.0%
8
  44.4%
14
  28.0%
Moderate
2
 100.0%
16
  53.3%
7
  38.9%
25
  50.0%
Severe
0
   0.0%
8
  26.7%
3
  16.7%
11
  22.0%
[1]
Measure Description: The chemotherapy (CTX) regimens administered included at least etoposide, doxorubicin, ifosfamide, or cyclophosphamide. The severity group (mild/moderate/severe) of myelotoxicity of the CTX regimens administered was assigned by a group of clinical experts, based on the scientific literature (Moreau et al 2009) and clinical experience.
1.Primary Outcome
Title Participants With Adverse Events (AEs)
Hide Description

An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. A treatment-emergent AE (TEAE) is an AE occurring during the timeframe. A non-TEAE is any AE not considered a TEAE.

Severity was rated by the investigator using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale where 3=severe but not life-threatening, 4=life-threatening and 5=death. Relation of AE to treatment was determined by the investigator (related=reasonable possibility). Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

Time Frame Non-TEAE: signing of informed consent to Day -1 (last day of CTX in week 1). And > 30 days after last dose of tbo-filgrastim (Day 46+). TEAE timeframe: Day 1 (start of tbo-filgrastim) to <= 30 days after the last dose (up to Day 45)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set. The safety analysis set included all enrolled patients who received at least 1 dose of tbofilgrastim.
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
Any adverse event 2 28 16
Any TEAE 2 28 15
Any non-TEAE 2 15 9
Any treatment-related TEAE 0 4 5
Any TEAE with NCI-CTCAE ToxicityGrade >=3 2 18 8
Any trt-related TEAE with Toxicity Grade >=3 0 1 2
Any serious TEAE 0 9 3
Any serious treatment-related TEAE 0 1 1
Any TEAE leading to discontinuation 0 0 0
Any treatment-related TEAE leading to discont 0 0 0
Any TEAE leading to death 0 0 0
Any treatment-related TEAE leading to death 0 0 0
2.Primary Outcome
Title Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results
Hide Description

Serum chemistry tests included alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin, indirect bilirubin, total bilirubin, calcium, creatinine, gammaglutamyl transpeptidase (GGT), glucose, potassium, lactate dehydrogenase (LDH), phosphate, sodium and uric acid.

Only tests with potentially clinically significant abnormal results are reported.

ULN = upper limit of normal

Time Frame Day 1 (start of tbo-filgrastim administration) up to Day 21
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Hide Analysis Population Description
Safety analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with >=1 abnormality 0 3 1
ALT: >20 * ULN 0 1 1
AST: >20 * ULN 0 1 0
AST: >5 * ULN and <= 20 * ULN 0 0 1
GGT: >5 * ULN and <= 20 * ULN 0 3 1
3.Primary Outcome
Title Participants With Potentially Clinically Significant Abnormal Hematology Results
Hide Description

Hematology tests included Basophils ABS (x 10^9/L), Basophils (%), Eosinophils ABS (x 10^9/L), Eosinophils (%), Hematocrit (%), Hemoglobin (g/L), Lymphocytes Absolute Count (ABS) (x 10^9/L), Lymphocytes (%), Monocytes ABS (x 10^9/L), Monocytes (%), Neutrophils ABS (x 10^9/L), Neutrophils (%), Platelets (x 10^9/L), Red Blood Cell (RBC) (x 10^12/L), White Blood Cell (WBC) (x 10^9/L).

Only tests with potentially clinically significant abnormal results are reported.

ULN = upper limit of normal

Time Frame Day 1 (start of tbo-filgrastim administration) up to Day 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with >=1 abnormality 2 6 3
Hemoglobin (g/L): <80 1 2 0
Hemoglobin (g/L): increase of >40 *ULN or baseline 0 0 1
Lymphocytes ABS (x 10^9/L): >=0.2 and <0.5 0 3 0
Neutrophils ABS (x 10^9/L): <0.5 1 1 1
Neutrophils ABS (x 10^9/L): >=0.5 and <1.0 1 1 1
Platelets (x 10^9/L): >=25 and <50 0 1 0
White Blood Cell (WBC) (x 10^9/L):<1.0 0 1 0
White Blood Cell (WBC) (x 10^9/L):>=1 and <2 1 3 1
4.Primary Outcome
Title Participants With Potentially Clinically Significant Abnormal Vital Signs
Hide Description

Vital sign tests included Pulse Rate (bpm), Systolic BP (mmHg), Diastolic BP (mmHg), Respiratory Rate (bpm), and Temperature (°C).

Only tests with potentially clinically significant abnormal results are reported.

Time Frame Day 1 (start of tbo-filgrastim administration) up to Day 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with >=1 abnormality 1 23 11
Pulse Rate (bpm): change of >=15 bpm 0 14 9
Systolic BP (mmHg): change of >=20mmHg 0 5 3
Diastolic BP (mmHg): change of >=15 mmHg 0 5 5
Respiratory Rate (bpm): change of >=8 breaths/min 0 5 0
Temperature (°C): >=38.0 °C 1 14 4
5.Primary Outcome
Title Participants With Potentially Clinically Significant Abnormal Electrocardiogram Results
Hide Description

Triplicate 12-lead ECGs were conducted at screening, predose, 4 and 6 hours postdose on day 1 of tbo-filgrastim administration, and at the end-of-study visit. The ECGs were interpreted by both the investigator and a qualified physician at the central diagnostic center as normal, abnormal not clinically significant, or abnormal clinically significant. The following parameters were measured/derived for each ECG assessment: heart rate, PR interval, RR interval, QT interval, corrected QT interval according to Fridericia’s formula (QTcF), corrected QT interval according to Bazett’s formula (QTcB), QRS duration, and QRS axis.

The count of participants with potentially clinically significant ECG findings is reported.

Time Frame Day 1 (start of tbo-filgrastim administration) pre-dose, 4 hours post dose and 6 hours post dose; Day 21 (end of study visit)
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Hide Analysis Population Description
Safety analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
0 0 0
6.Primary Outcome
Title Participants With Negative Shifts From Baseline to End of Study in Physical Exam Findings
Hide Description

Physical examination was performed at screening and at the end-of-study visit. The following body systems were marked as normal or abnormal and if abnormal, whether clinically significant: Head, ears, eyes, nose and throat (HEENT), chest and lungs, heart, abdomen, skin, lymph nodes and neurological.

Any physical examination finding that is judged by the investigator as a clinically significant change (worsening) compared with a baseline value were considered as an adverse event.

Counts of participants with a negative shift from baseline in any of the body systems (including shifts from normal to abnormal, not clinically significant) are presented.

Time Frame Baseline: Day -21, Day 21 (end of study visit)
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Safety analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
HEENT 0 0 0
Chest and lungs 0 0 0
Heart 0 0 0
Abdomen 0 0 0
Skin 0 1 0
Lymph nodes 0 0 0
Neurological 0 0 0
7.Primary Outcome
Title Participants With Injection Site Reactions to Tbo-Filgrastim Administration
Hide Description Using Local Tolerability Assessment Scale ranging from Pain severity 0 (Absent) to 3 (Spontaneously painful)
Time Frame Day 1 (start of tbo-filgrastim administration) up to Day 14
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Hide Analysis Population Description
Safety analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
Surface ecchymosis 2 7 2
Surface erythema/redness 2 2 0
Induration 0 1 0
Pain at the injection site 0 0 0
8.Primary Outcome
Title Participants With Negative Shifts From Baseline to End of Study in Spleen Sonography Findings
Hide Description

The investigator assessed spleen sonography findings as normal, abnormal not clinically significant, or abnormal clinically significant.

Data representing counts of participants with a negative shift from baseline in spleen sonography findings (including shifts from normal to abnormal, not clinically significant) are presented.

Time Frame Baseline: Day -21, Day 21 (end of study visit)
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Hide Analysis Population Description
Safety analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
0 0 0
9.Primary Outcome
Title Participants Who Were Alive at the 90 Day Follow-Up
Hide Description Summary of participant survival at 90 day follow-up.
Time Frame 90 days post end of study visit (111 days from start of tbo-filgrastim administration)
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Hide Analysis Population Description
Safety analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
2 30 18
10.Secondary Outcome
Title Participants With Positive Immunogenicity Findings Tested at Four Study Timepoints
Hide Description

Blood was drawn for the assessment of anti-drug antibody (ADA) at screening, at the end-of-study visit, and at 30 and 90 days after the last administration of tbo-filgrastim in chemotherapy (CTX) cycle 1.

The main endpoint from the assessment was the presence of antibodies in the sample, reported as positive or negative. Participants with positive results are summarized.

Time Frame Baseline (Day -21), Day 21 (end of study visit), Day 51 (30 Day follow-up) and Day 111 (90 Day follow-up)
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Hide Analysis Population Description
Safety analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
Screening 0 0 0
End of Study visit 0 0 0
30 Day Follow-up 0 0 0
90 Day Follow-up 0 0 0
11.Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of Tbo-Filgrastim
Hide Description [Not Specified]
Time Frame Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 29 18
Mean (Standard Deviation)
Unit of Measure: pg/mL
26087.95  (8647.562) 20048.27  (9232.446) 19032.60  (11086.273)
12.Secondary Outcome
Title Time to Maximum Observed Serum Concentration (Tmax) of Tbo-Filgrastim
Hide Description [Not Specified]
Time Frame Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 29 18
Median (Full Range)
Unit of Measure: Hours
6.00
(6.0 to 6.0)
4.07
(3.9 to 8.0)
4.00
(3.9 to 8.0)
13.Secondary Outcome
Title Area Under The Serum Concentration-Time Curve From Time 0 To Time Of Last Quantifiable Concentration (AUClast)
Hide Description [Not Specified]
Time Frame Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 29 18
Mean (Standard Deviation)
Unit of Measure: hr*pg/mL
187889.69  (80122.148) 142124.91  (63127.420) 127447.08  (73894.137)
14.Secondary Outcome
Title Area Under The Serum Concentration-Time Curve From Time 0 To 12 Hours Postdose (AUC0-12)
Hide Description [Not Specified]
Time Frame Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. In 4 participants, serum concentrations of tbo-filgrastim were not obtained through 12 hours and as a result, AUC0-12 could not be calculated.
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 28 15
Mean (Standard Deviation)
Unit of Measure: hr*pg/mL
187889.69  (80122.148) 144109.32  (63358.011) 140550.22  (73648.629)
15.Secondary Outcome
Title AUC From Time 0 to Infinity (AUC0-inf)
Hide Description [Not Specified]
Time Frame Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. The 12 hour sampling duration limited the ability to characterize the terminal elimination rate of tbo-filgrastim (λz ) and related parameters (t½, AUC0-∞,-∞ %AUCex, CL/F, and Vz/F) for more than half of patients enrolled, especially those with maximum serum concentrations being achieved >= 6 hours. This included both infants.
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 0 15 8
Mean (Standard Deviation)
Unit of Measure: hr*pg/mL
161964.32  (87205.040) 198470.33  (80773.023)
16.Secondary Outcome
Title Elimination Half-life (t1/2)
Hide Description [Not Specified]
Time Frame Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. The 12 hour sampling duration limited the ability to characterize the terminal elimination rate of tbo-filgrastim (λz ) and related parameters (t½, AUC0-∞,-∞ %AUCex, CL/F, and Vz/F) for more than half of patients enrolled, especially those with maximum serum concentrations being achieved >= 6 hours. This included both infants.
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 0 15 8
Mean (Standard Deviation)
Unit of Measure: hours
2.41  (0.549) 2.52  (0.561)
17.Secondary Outcome
Title Apparent Clearance (CL/F)
Hide Description [Not Specified]
Time Frame Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose of Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. The 12 hour sampling duration limited the ability to characterize the terminal elimination rate of tbo-filgrastim (λz ) and related parameters (t½, AUC0-∞,-∞ %AUCex, CL/F, and Vz/F) for more than half of patients enrolled, especially those with maximum serum concentrations being achieved >= 6 hours. This included both infants.
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 0 15 8
Mean (Standard Deviation)
Unit of Measure: L/hour
0.98  (0.719) 1.68  (0.748)
18.Secondary Outcome
Title Apparent Volume of Distribution During the Terminal Phase (Vz/F)
Hide Description [Not Specified]
Time Frame Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. The 12 hour sampling duration limited the ability to characterize the terminal elimination rate of tbo-filgrastim (λz ) and related parameters (t½, AUC0-∞,-∞ %AUCex, CL/F, and Vz/F) for more than half of patients enrolled, especially those with maximum serum concentrations being achieved >= 6 hours. This included both infants.
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 0 15 8
Mean (Standard Deviation)
Unit of Measure: liters
3.21  (1.963) 6.13  (3.094)
19.Secondary Outcome
Title Percentage of the AUC0–∞ That Is Due To the Extrapolation (%AUCext)
Hide Description [Not Specified]
Time Frame Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. The 12 hour sampling duration limited the ability to characterize the terminal elimination rate of tbo-filgrastim (λz ) and related parameters (t½, AUC0-∞,-∞ %AUCex, CL/F, and Vz/F) for more than half of patients enrolled, especially those with maximum serum concentrations being achieved >= 6 hours. This included both infants.
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 0 15 8
Mean (Standard Deviation)
Unit of Measure: percent of AUC0–∞
7.97  (4.179) 8.19  (4.424)
20.Secondary Outcome
Title Terminal Elimination Rate (Lambda-z)
Hide Description [Not Specified]
Time Frame Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK analysis set. The 12 hour sampling duration limited the ability to characterize the terminal elimination rate of tbo-filgrastim (λz ) and related parameters (t½, AUC0-∞,-∞ %AUCex, CL/F, and Vz/F) for more than half of patients enrolled, especially those with maximum serum concentrations being achieved >= 6 hours. This included both infants.
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 0 15 8
Mean (Standard Deviation)
Unit of Measure: 1/hr
.30  (0.077) .29  (0.067)
21.Secondary Outcome
Title Participants With Severe Neutropenia
Hide Description Count of participants who had an incidence of severe neutropenia, defined as any value of absolute neutrophil count (ANC) <0.5 * 10^9/L at any time.
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) included all patients in the ITT population who received at least 1 dose of tbo-filgrastim and had at least 1 post baseline efficacy assessment.
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with event 1 19 6
Participants without event 1 11 12
22.Secondary Outcome
Title Duration of Severe Neutropenia
Hide Description The duration of severe neutropenia was derived by counting the number of days with absolute neutrophil count (ANC) values <0.5 * 10^9/L.
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Mean (Standard Deviation)
Unit of Measure: days
1.5  (2.12) 2.5  (2.46) 0.7  (1.14)
23.Secondary Outcome
Title Area Under The Serum Drug Concentration By Time Curve Of Absolute Neutrophil Count (AUC ANC)
Hide Description [Not Specified]
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Mean (Standard Deviation)
Unit of Measure: *10^9/L * days
20.465  (6.1235) 53.931  (44.8741) 87.098  (61.1857)
24.Secondary Outcome
Title Absolute Neutrophil Count (ANC) Nadir
Hide Description ANC nadir (measured in 10^9/L) is the lowest ANC recorded.
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Mean (Standard Deviation)
Unit of Measure: *10^9/L
0.490  (0.4808) 0.851  (1.3633) 0.832  (0.6358)
25.Secondary Outcome
Title Time to Absolute Neutrophil Count (ANC) Nadir From Beginning of Tbo-filgrastim Administration
Hide Description [Not Specified]
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Mean (Standard Deviation)
Unit of Measure: days
3.0  (4.24) 6.9  (2.55) 7.3  (2.72)
26.Secondary Outcome
Title Time to Absolute Neutrophil Count (ANC) Nadir From Beginning of Chemotherapy
Hide Description [Not Specified]
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Mean (Standard Deviation)
Unit of Measure: days
6.5  (2.12) 10.3  (2.86) 11.2  (2.31)
27.Secondary Outcome
Title Time to ANC Recovery To ≥1.0 * 10^9/L From ANC Nadir
Hide Description [Not Specified]
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Mean (Standard Deviation)
Unit of Measure: days
10.0  (7.07) 2.2  (2.02) 1.0  (1.19)
28.Secondary Outcome
Title Time to ANC Recovery To ≥2.0 * 10^9/L From ANC Nadir
Hide Description [Not Specified]
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Mean (Standard Deviation)
Unit of Measure: days
13.0  (2.83) 3.0  (3.09) 2.8  (2.09)
29.Secondary Outcome
Title Time to ANC Recovery To ≥1.0 * 10^9/L From Start of Tbo-filgrastim Administration
Hide Description [Not Specified]
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Mean (Standard Deviation)
Unit of Measure: days
13.0  (2.83) 7.3  (4.43) 5.1  (5.30)
30.Secondary Outcome
Title Time to ANC Recovery To ≥2.0 * 10^9/L From Start of Tbo-filgrastim Administration
Hide Description [Not Specified]
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Mean (Standard Deviation)
Unit of Measure: days
16.0  (1.41) 8.1  (5.20) 10.2  (4.22)
31.Secondary Outcome
Title Time to ANC Recovery To ≥1.0 * 10^9/L From Start of Chemotherapy
Hide Description [Not Specified]
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Mean (Standard Deviation)
Unit of Measure: days
16.5  (4.95) 10.2  (5.98) 7.4  (7.09)
32.Secondary Outcome
Title Time to ANC Recovery To ≥2.0 * 10^9/L From Start of Chemotherapy
Hide Description [Not Specified]
Time Frame ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Mean (Standard Deviation)
Unit of Measure: days
19.5  (0.71) 11.0  (6.52) 14.0  (3.73)
33.Secondary Outcome
Title Participants With Febrile Neutropenia During the First Cycle of Chemotherapy
Hide Description Febrile neutropenia was defined as an axillary or external ear temperature >38.3°C (100.94°F) or 2 consecutive readings >37.8°C (100.04°F) at least 2 hours apart and an ANC <0.5 * 10^9/L. The efficacy variable was evaluated for up to 21 days from the start of the first cycle of chemotherapy.
Time Frame (relative to tbo-filgrastim therapy) Days -7 to Day 14
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Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description:
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
Overall Number of Participants Analyzed 2 30 18
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with event 1 9 3
Participants without event 1 21 15
Time Frame Day 1 (start of tbo-filgrastim administration) to <= 30 days after the last dose (up to Day 45)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Hide Arm/Group Description Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle. Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle. Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last chemotherapy (CTX) treatment in the first week of the CTX cycle. Daily dosing with tbo-filgrastim at a dose of 5 μg/kg/day of body weight continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 10^9/L but not longer than 14 consecutive days. An immunogenicity sample was collected 30 days and 3 months after the last tbo-filgrastim administration in the first cycle.
All-Cause Mortality
Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/2 (0.00%)      0/30 (0.00%)      0/18 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/2 (0.00%)      9/30 (30.00%)      3/18 (16.67%)    
Blood and lymphatic system disorders       
Anaemia  1  0/2 (0.00%)  0 4/30 (13.33%)  5 0/18 (0.00%)  0
Febrile neutropenia  1  0/2 (0.00%)  0 4/30 (13.33%)  6 2/18 (11.11%)  2
Pancytopenia  1  0/2 (0.00%)  0 1/30 (3.33%)  1 0/18 (0.00%)  0
Thrombocytopenia  1  0/2 (0.00%)  0 2/30 (6.67%)  2 2/18 (11.11%)  2
Gastrointestinal disorders       
Haematemesis  1  0/2 (0.00%)  0 1/30 (3.33%)  1 0/18 (0.00%)  0
Investigations       
Alanine aminotransferase increased  1  0/2 (0.00%)  0 2/30 (6.67%)  2 1/18 (5.56%)  1
Aspartate aminotransferase increased  1  0/2 (0.00%)  0 2/30 (6.67%)  2 1/18 (5.56%)  1
Gamma-glutamyltransferase increased  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  1
Skin and subcutaneous tissue disorders       
Hangnail  1  0/2 (0.00%)  0 1/30 (3.33%)  1 0/18 (0.00%)  0
1
Term from vocabulary, MedDRA 17.0
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 5%
Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/2 (100.00%)      27/30 (90.00%)      15/18 (83.33%)    
Blood and lymphatic system disorders       
Anaemia  1  1/2 (50.00%)  1 12/30 (40.00%)  20 3/18 (16.67%)  3
Febrile neutropenia  1  1/2 (50.00%)  1 5/30 (16.67%)  5 0/18 (0.00%)  0
Leukopenia  1  2/2 (100.00%)  2 6/30 (20.00%)  11 3/18 (16.67%)  3
Lymphopenia  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  3
Neutropenia  1  2/2 (100.00%)  6 16/30 (53.33%)  34 9/18 (50.00%)  16
Thrombocytopenia  1  2/2 (100.00%)  5 8/30 (26.67%)  16 4/18 (22.22%)  5
Cardiac disorders       
Sinus tachycardia  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  1
Gastrointestinal disorders       
Abdominal pain upper  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  2
Abdominal rigidity  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  1
Colitis  1  1/2 (50.00%)  1 1/30 (3.33%)  1 0/18 (0.00%)  0
Constipation  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  1
Diarrhoea  1  0/2 (0.00%)  0 2/30 (6.67%)  2 1/18 (5.56%)  2
Enterocolitis  1  1/2 (50.00%)  1 0/30 (0.00%)  0 0/18 (0.00%)  0
Nausea  1  0/2 (0.00%)  0 2/30 (6.67%)  2 2/18 (11.11%)  2
Stomatitis  1  1/2 (50.00%)  1 3/30 (10.00%)  3 2/18 (11.11%)  2
Vomiting  1  0/2 (0.00%)  0 5/30 (16.67%)  6 3/18 (16.67%)  6
General disorders       
Hyperthermia  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  1
Mucosal inflammation  1  0/2 (0.00%)  0 3/30 (10.00%)  3 3/18 (16.67%)  3
Pyrexia  1  0/2 (0.00%)  0 2/30 (6.67%)  2 2/18 (11.11%)  10
Immune system disorders       
Hypogammaglobulinaemia  1  0/2 (0.00%)  0 0/30 (0.00%)  0 3/18 (16.67%)  6
Infections and infestations       
Cellulitis staphylococcal  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  1
Clostridium difficile colitis  1  0/2 (0.00%)  0 1/30 (3.33%)  1 1/18 (5.56%)  2
Oral candidiasis  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  1
Investigations       
Alanine aminotransferase increased  1  0/2 (0.00%)  0 2/30 (6.67%)  2 0/18 (0.00%)  0
Aspartate aminotransferase increased  1  0/2 (0.00%)  0 2/30 (6.67%)  2 0/18 (0.00%)  0
Blood lactate dehydrogenase increased  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  1
Gamma-glutamyltransferase increased  1  0/2 (0.00%)  0 2/30 (6.67%)  2 0/18 (0.00%)  0
Neutrophil count decreased  1  0/2 (0.00%)  0 2/30 (6.67%)  3 0/18 (0.00%)  0
White blood cell count decreased  1  0/2 (0.00%)  0 2/30 (6.67%)  3 0/18 (0.00%)  0
Metabolism and nutrition disorders       
Decreased appetite  1  0/2 (0.00%)  0 2/30 (6.67%)  2 0/18 (0.00%)  0
Hypoalbuminaemia  1  0/2 (0.00%)  0 0/30 (0.00%)  0 2/18 (11.11%)  4
Hypokalaemia  1  0/2 (0.00%)  0 1/30 (3.33%)  1 1/18 (5.56%)  1
Musculoskeletal and connective tissue disorders       
Back pain  1  0/2 (0.00%)  0 1/30 (3.33%)  1 1/18 (5.56%)  1
Pain in extremity  1  0/2 (0.00%)  0 2/30 (6.67%)  2 1/18 (5.56%)  4
Nervous system disorders       
Headache  1  0/2 (0.00%)  0 1/30 (3.33%)  1 2/18 (11.11%)  2
Neurotoxicity  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  1
Skin and subcutaneous tissue disorders       
Rash vesicular  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  1
Skin necrosis  1  0/2 (0.00%)  0 0/30 (0.00%)  0 1/18 (5.56%)  1
1
Term from vocabulary, MedDRA 17.0
Indicates events were collected by systematic assessment
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.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc.
Phone: 215-591-3000
Responsible Party: Teva Pharmaceutical Industries ( Teva Pharmaceutical Industries, Ltd. )
ClinicalTrials.gov Identifier: NCT02190721     History of Changes
Other Study ID Numbers: XM02-ONC-201
2014-001772-55 ( EudraCT Number )
First Submitted: July 11, 2014
First Posted: July 15, 2014
Results First Submitted: May 18, 2018
Results First Posted: July 31, 2018
Last Update Posted: July 31, 2018