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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

Sponsor
Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02190721
Collaborator
(none)
50
Enrollment
33
Locations
1
Arm
22.8
Actual Duration (Months)
1.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of daily subcutaneous administration of 5 μg/kg tbo-filgrastim in infants, children and adolescents with solid tumors without bone marrow involvement.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
50 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Efficacy, and Immunogenicity of Daily Subcutaneous Administration of 5 ?g/kg Tbo-filgrastim in Infants, Children and Adolescents With Solid Tumors Without Bone Marrow Involvement
Actual Study Start Date :
May 12, 2015
Actual Primary Completion Date :
Apr 4, 2017
Actual Study Completion Date :
Apr 4, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: tbo-filgrastim

Patients will receive subcutaneous doses of tbo-filgrastim 5 μg/kg body weight daily; each daily dose, to be administered at the investigative site

Drug: tbo-filgrastim
5 μg/kg

Outcome Measures

Primary Outcome Measures

  1. Participants With Adverse Events (AEs) [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)]

    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.

  2. Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results [Day 1 (start of tbo-filgrastim administration) up to Day 21]

    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

  3. Participants With Potentially Clinically Significant Abnormal Hematology Results [Day 1 (start of tbo-filgrastim administration) up to Day 21]

    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

  4. Participants With Potentially Clinically Significant Abnormal Vital Signs [Day 1 (start of tbo-filgrastim administration) up to Day 21]

    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.

  5. Participants With Potentially Clinically Significant Abnormal Electrocardiogram Results [Day 1 (start of tbo-filgrastim administration) pre-dose, 4 hours post dose and 6 hours post dose; Day 21 (end of study visit)]

    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.

  6. Participants With Negative Shifts From Baseline to End of Study in Physical Exam Findings [Baseline: Day -21, Day 21 (end of study visit)]

    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.

  7. Participants With Injection Site Reactions to Tbo-Filgrastim Administration [Day 1 (start of tbo-filgrastim administration) up to Day 14]

    Using Local Tolerability Assessment Scale ranging from Pain severity 0 (Absent) to 3 (Spontaneously painful)

  8. Participants With Negative Shifts From Baseline to End of Study in Spleen Sonography Findings [Baseline: Day -21, Day 21 (end of study visit)]

    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.

  9. Participants Who Were Alive at the 90 Day Follow-Up [90 days post end of study visit (111 days from start of tbo-filgrastim administration)]

    Summary of participant survival at 90 day follow-up.

Secondary Outcome Measures

  1. Participants With Positive Immunogenicity Findings Tested at Four Study Timepoints [Baseline (Day -21), Day 21 (end of study visit), Day 51 (30 Day follow-up) and Day 111 (90 Day follow-up)]

    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.

  2. Maximum Observed Serum Concentration (Cmax) of Tbo-Filgrastim [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]

  3. Time to Maximum Observed Serum Concentration (Tmax) of Tbo-Filgrastim [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]

  4. Area Under The Serum Concentration-Time Curve From Time 0 To Time Of Last Quantifiable Concentration (AUClast) [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]

  5. Area Under The Serum Concentration-Time Curve From Time 0 To 12 Hours Postdose (AUC0-12) [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]

  6. AUC From Time 0 to Infinity (AUC0-inf) [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]

  7. Elimination Half-life (t1/2) [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]

  8. Apparent Clearance (CL/F) [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]

  9. Apparent Volume of Distribution During the Terminal Phase (Vz/F) [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]

  10. Percentage of the AUC0-∞ That Is Due To the Extrapolation (%AUCext) [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]

  11. Terminal Elimination Rate (Lambda-z) [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]

  12. Participants With Severe Neutropenia [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)]

    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.

  13. Duration of Severe Neutropenia [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)]

    The duration of severe neutropenia was derived by counting the number of days with absolute neutrophil count (ANC) values <0.5 * 10^9/L.

  14. Area Under The Serum Drug Concentration By Time Curve Of Absolute Neutrophil Count (AUC ANC) [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)]

  15. Absolute Neutrophil Count (ANC) Nadir [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)]

    ANC nadir (measured in 10^9/L) is the lowest ANC recorded.

  16. Time to Absolute Neutrophil Count (ANC) Nadir From Beginning of Tbo-filgrastim Administration [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)]

  17. Time to Absolute Neutrophil Count (ANC) Nadir From Beginning of Chemotherapy [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)]

  18. Time to ANC Recovery To ≥1.0 * 10^9/L From ANC Nadir [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)]

  19. Time to ANC Recovery To ≥2.0 * 10^9/L From ANC Nadir [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)]

  20. Time to ANC Recovery To ≥1.0 * 10^9/L From Start of Tbo-filgrastim Administration [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)]

  21. Time to ANC Recovery To ≥2.0 * 10^9/L From Start of Tbo-filgrastim Administration [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)]

  22. Time to ANC Recovery To ≥1.0 * 10^9/L From Start of Chemotherapy [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)]

  23. Time to ANC Recovery To ≥2.0 * 10^9/L From Start of Chemotherapy [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)]

  24. Participants With Febrile Neutropenia During the First Cycle of Chemotherapy [(relative to tbo-filgrastim therapy) Days -7 to Day 14]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Month to 16 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion:

  1. Male or female infants, children and adolescents aged 1 month to <16 years.

  2. Patients with solid tumors without bone marrow involvement, who are scheduled to receive myelosuppressive CTX.

  3. Body weight ≥5 kg.

  4. Patients must have an initial diagnosis and histologic proof of their malignancy. All enrolled subjects should have signed consent for a CTX regimen that is known to be myelotoxic, with counts expected to drop below the absolute neutrophil count (ANC) of 0.5 × 109/L for at least 3 days. These regimens would include at least one of the following:

  • Etoposide

  • doxorubicin

  • ifosfamide

  • cyclophosphamide

  1. ANC and platelet count: Patients must have an ANC >1 × 109/L and a platelet count >100 × 109/L to be eligible for therapy at the start of CTX.

  2. Normal cardiac, renal, and hepatic function.

  3. All subjects must have a life expectancy of 12 weeks or more.

  4. Performance Status: Lansky performance score >60 (age 1 to <16 years).

  • More criteria may apply, please contact the investigator for more information.
Exclusion:

  1. Bone marrow involvement.

  2. Active myelogenous leukemia or history of myelogenous leukemia.

  3. Previous treatment with colony-stimulating factors (granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, interleukin 11 [IL-11]) less than 6 weeks prior to study entry.

  4. History of congenital neutropenia or cyclic neutropenia.

  5. Pregnant or nursing female patients.

  6. Fertile patients who do not agree to use highly reliable contraceptive measures Prior bone marrow or stem cell transplant, or prior radiation to ≥25% of bone marrow within the 4 weeks prior to the first tbo-filgrastim dose.

  7. Ongoing active infection or history of infectious disease within 2 weeks prior to the screening visit.

  8. Treatment with lithium at screening or planned during the study

  • More criteria may apply, please contact the investigator for more information.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Teva Investigational Site 12958 Long Beach California United States 90806
2 Teva Investigational Site 12951 Los Angeles California United States 90024
3 Teva Investigational Site 12954 Jackson Mississippi United States 39216
4 Teva Investigational Site 12953 Las Vegas Nevada United States 89109
5 Teva Investigational Site 12959 Valhalla New York United States 10595
6 Teva Investigational Site 12960 Columbus Ohio United States 43205
7 Teva Investigational Site 12957 Houston Texas United States 77030
8 Teva Investigational Site 59104 Sofia Bulgaria 15257
9 Teva Investigational Site 59105 Varna Bulgaria 9010
10 Teva Investigational Site 60015 Rijeka Croatia 51000
11 Teva Investigational Site 60014 Zagreb Croatia 10000
12 Teva Investigational Site 60016 Zagreb Croatia 10000
13 Teva Investigational Site 51186 Budapest Hungary 1089
14 Teva Investigational Site 51185 Budapest Hungary 1094
15 Teva Investigational Site 51184 Szeged Hungary 6725
16 Teva Investigational Site 53249 Gdansk Poland 80-952
17 Teva Investigational Site 53248 Lublin Poland 20-093
18 Teva Investigational Site 53245 Warszawa Poland 01-211
19 Teva Investigational Site 53246 Warszawa Poland 04-730
20 Teva Investigational Site 53247 Wroclaw Poland 50-556
21 Teva Investigational Site 52063 Bucharest Romania 022328
22 Teva Investigational Site 52064 Cluj-Napoca, Cluj Romania 400015
23 Teva Investigational Site 52065 Timisoara Romania 300383
24 Teva Investigational Site 50282 Chelyabinsk Russian Federation 454076
25 Teva Investigational Site 50281 Krasnodar Russian Federation 350007
26 Teva Investigational Site 50284 Moscow Russian Federation 117198
27 Teva Investigational Site 50280 St. Petersburg Russian Federation 197110
28 Teva Investigational Site 50283 Volgograd Russian Federation 400138
29 Teva Investigational Site 58147 Kharkiv Ukraine 61070
30 Teva Investigational Site 58145 Kyiv Ukraine 03022
31 Teva Investigational Site 58148 Lviv Ukraine 79035
32 Teva Investigational Site 58146 Vinnytsya Ukraine 21029
33 Teva Investigational Site 58149 Vinnytsya Ukraine 21029

Sponsors and Collaborators

  • Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

  • Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Teva Branded Pharmaceutical Products R&D, Inc.
ClinicalTrials.gov Identifier:
NCT02190721
Other Study ID Numbers:
  • XM02-ONC-201
  • 2014-001772-55
First Posted:
Jul 15, 2014
Last Update Posted:
Dec 10, 2021
Last Verified:
Dec 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.
Neutropenia
Additional relevant MeSH terms:
Neutropenia
Lenograstim

Study Results

Participant Flow

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 Detail 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)
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

Baseline Characteristics

Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years) Total
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 Participants 2 30 18 50
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]
1.65
6.80
13.80
9.05
Sex: Female, Male (Count of Participants)
Female
1
50%
13
43.3%
6
33.3%
20
40%
Male
1
50%
17
56.7%
12
66.7%
30
60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
0
0%
Not Hispanic or Latino
2
100%
30
100%
18
100%
50
100%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
Black or African American
0
0%
0
0%
0
0%
0
0%
White
2
100%
30
100%
18
100%
50
100%
More than one race
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
Weight (kg) [Median (Full Range) ]
Median (Full Range) [kg]
9.90
20.25
53.90
28.95
Height (cm) [Median (Full Range) ]
Median (Full Range) [cm]
78.00
121.00
161.00
130.50
Body Mass Index (kg/m^2) [Median (Full Range) ]
Median (Full Range) [kg/m^2]
16.0
15.2
20.7
16.4
Chemotherapy Administration (Count of Participants)
Mild
0
0%
6
20%
8
44.4%
14
28%
Moderate
2
100%
16
53.3%
7
38.9%
25
50%
Severe
0
0%
8
26.7%
3
16.7%
11
22%

Outcome Measures

1. Primary Outcome
Title Participants With Adverse Events (AEs)
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)

Outcome Measure Data

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)
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.
Measure Participants 2 30 18
Any adverse event
2
100%
28
93.3%
16
88.9%
Any TEAE
2
100%
28
93.3%
15
83.3%
Any non-TEAE
2
100%
15
50%
9
50%
Any treatment-related TEAE
0
0%
4
13.3%
5
27.8%
Any TEAE with NCI-CTCAE ToxicityGrade >=3
2
100%
18
60%
8
44.4%
Any trt-related TEAE with Toxicity Grade >=3
0
0%
1
3.3%
2
11.1%
Any serious TEAE
0
0%
9
30%
3
16.7%
Any serious treatment-related TEAE
0
0%
1
3.3%
1
5.6%
Any TEAE leading to discontinuation
0
0%
0
0%
0
0%
Any treatment-related TEAE leading to discont
0
0%
0
0%
0
0%
Any TEAE leading to death
0
0%
0
0%
0
0%
Any treatment-related TEAE leading to death
0
0%
0
0%
0
0%
2. Primary Outcome
Title Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results
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

Outcome Measure Data

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)
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.
Measure Participants 2 30 18
Participants with >=1 abnormality
0
0%
3
10%
1
5.6%
ALT: >20 * ULN
0
0%
1
3.3%
1
5.6%
AST: >20 * ULN
0
0%
1
3.3%
0
0%
AST: >5 * ULN and <= 20 * ULN
0
0%
0
0%
1
5.6%
GGT: >5 * ULN and <= 20 * ULN
0
0%
3
10%
1
5.6%
3. Primary Outcome
Title Participants With Potentially Clinically Significant Abnormal Hematology Results
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

Outcome Measure Data

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)
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.
Measure Participants 2 30 18
Participants with >=1 abnormality
2
100%
6
20%
3
16.7%
Hemoglobin (g/L): <80
1
50%
2
6.7%
0
0%
Hemoglobin (g/L): increase of >40 *ULN or baseline
0
0%
0
0%
1
5.6%
Lymphocytes ABS (x 10^9/L): >=0.2 and <0.5
0
0%
3
10%
0
0%
Neutrophils ABS (x 10^9/L): <0.5
1
50%
1
3.3%
1
5.6%
Neutrophils ABS (x 10^9/L): >=0.5 and <1.0
1
50%
1
3.3%
1
5.6%
Platelets (x 10^9/L): >=25 and <50
0
0%
1
3.3%
0
0%
White Blood Cell (WBC) (x 10^9/L):<1.0
0
0%
1
3.3%
0
0%
White Blood Cell (WBC) (x 10^9/L):>=1 and <2
1
50%
3
10%
1
5.6%
4. Primary Outcome
Title Participants With Potentially Clinically Significant Abnormal Vital Signs
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

Outcome Measure Data

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)
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.
Measure Participants 2 30 18
Participants with >=1 abnormality
1
50%
23
76.7%
11
61.1%
Pulse Rate (bpm): change of >=15 bpm
0
0%
14
46.7%
9
50%
Systolic BP (mmHg): change of >=20mmHg
0
0%
5
16.7%
3
16.7%
Diastolic BP (mmHg): change of >=15 mmHg
0
0%
5
16.7%
5
27.8%
Respiratory Rate (bpm): change of >=8 breaths/min
0
0%
5
16.7%
0
0%
Temperature (°C): >=38.0 °C
1
50%
14
46.7%
4
22.2%
5. Primary Outcome
Title Participants With Potentially Clinically Significant Abnormal Electrocardiogram Results
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)

Outcome Measure Data

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)
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.
Measure Participants 2 30 18
Count of Participants [Participants]
0
0%
0
0%
0
0%
6. Primary Outcome
Title Participants With Negative Shifts From Baseline to End of Study in Physical Exam Findings
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)

Outcome Measure Data

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)
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.
Measure Participants 2 30 18
HEENT
0
0%
0
0%
0
0%
Chest and lungs
0
0%
0
0%
0
0%
Heart
0
0%
0
0%
0
0%
Abdomen
0
0%
0
0%
0
0%
Skin
0
0%
1
3.3%
0
0%
Lymph nodes
0
0%
0
0%
0
0%
Neurological
0
0%
0
0%
0
0%
7. Primary Outcome
Title Participants With Injection Site Reactions to Tbo-Filgrastim Administration
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

Outcome Measure Data

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)
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.
Measure Participants 2 30 18
Surface ecchymosis
2
100%
7
23.3%
2
11.1%
Surface erythema/redness
2
100%
2
6.7%
0
0%
Induration
0
0%
1
3.3%
0
0%
Pain at the injection site
0
0%
0
0%
0
0%
8. Primary Outcome
Title Participants With Negative Shifts From Baseline to End of Study in Spleen Sonography Findings
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)

Outcome Measure Data

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)
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.
Measure Participants 2 30 18
Count of Participants [Participants]
0
0%
0
0%
0
0%
9. Primary Outcome
Title Participants Who Were Alive at the 90 Day Follow-Up
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)

Outcome Measure Data

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)
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.
Measure Participants 2 30 18
Count of Participants [Participants]
2
100%
30
100%
18
100%
10. Secondary Outcome
Title Participants With Positive Immunogenicity Findings Tested at Four Study Timepoints
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)

Outcome Measure Data

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)
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.
Measure Participants 2 30 18
Screening
0
0%
0
0%
0
0%
End of Study visit
0
0%
0
0%
0
0%
30 Day Follow-up
0
0%
0
0%
0
0%
90 Day Follow-up
0
0%
0
0%
0
0%
11. Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of Tbo-Filgrastim
Description
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

Outcome Measure Data

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)
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.
Measure Participants 2 29 18
Mean (Standard Deviation) [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
Description
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

Outcome Measure Data

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)
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.
Measure Participants 2 29 18
Median (Full Range) [Hours]
6.00
4.07
4.00
13. Secondary Outcome
Title Area Under The Serum Concentration-Time Curve From Time 0 To Time Of Last Quantifiable Concentration (AUClast)
Description
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

Outcome Measure Data

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)
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.
Measure Participants 2 29 18
Mean (Standard Deviation) [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)
Description
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

Outcome Measure Data

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)
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.
Measure Participants 2 28 15
Mean (Standard Deviation) [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)
Description
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

Outcome Measure Data

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)
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.
Measure Participants 0 15 8
Mean (Standard Deviation) [hr*pg/mL]
161964.32
(87205.040)
198470.33
(80773.023)
16. Secondary Outcome
Title Elimination Half-life (t1/2)
Description
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

Outcome Measure Data

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)
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.
Measure Participants 0 15 8
Mean (Standard Deviation) [hours]
2.41
(0.549)
2.52
(0.561)
17. Secondary Outcome
Title Apparent Clearance (CL/F)
Description
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

Outcome Measure Data

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)
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.
Measure Participants 0 15 8
Mean (Standard Deviation) [L/hour]
0.98
(0.719)
1.68
(0.748)
18. Secondary Outcome
Title Apparent Volume of Distribution During the Terminal Phase (Vz/F)
Description
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

Outcome Measure Data

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)
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.
Measure Participants 0 15 8
Mean (Standard Deviation) [liters]
3.21
(1.963)
6.13
(3.094)
19. Secondary Outcome
Title Percentage of the AUC0-∞ That Is Due To the Extrapolation (%AUCext)
Description
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

Outcome Measure Data

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)
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.
Measure Participants 0 15 8
Mean (Standard Deviation) [percent of AUC0-∞]
7.97
(4.179)
8.19
(4.424)
20. Secondary Outcome
Title Terminal Elimination Rate (Lambda-z)
Description
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

Outcome Measure Data

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)
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.
Measure Participants 0 15 8
Mean (Standard Deviation) [1/hr]
.30
(0.077)
.29
(0.067)
21. Secondary Outcome
Title Participants With Severe Neutropenia
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)

Outcome Measure Data

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)
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.
Measure Participants 2 30 18
Participants with event
1
50%
19
63.3%
6
33.3%
Participants without event
1
50%
11
36.7%
12
66.7%
22. Secondary Outcome
Title Duration of Severe Neutropenia
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)

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Mean (Standard Deviation) [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)
Description
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)

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Mean (Standard Deviation) [*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
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)

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Mean (Standard Deviation) [*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
Description
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)

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Mean (Standard Deviation) [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
Description
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)

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Mean (Standard Deviation) [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
Description
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)

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Mean (Standard Deviation) [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
Description
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)

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Mean (Standard Deviation) [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
Description
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)

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Mean (Standard Deviation) [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
Description
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)

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Mean (Standard Deviation) [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
Description
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)

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Mean (Standard Deviation) [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
Description
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)

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Mean (Standard Deviation) [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
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

Outcome Measure Data

Analysis Population Description
Full analysis set
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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.
Measure Participants 2 30 18
Participants with event
1
50%
9
30%
3
16.7%
Participants without event
1
50%
21
70%
15
83.3%

Adverse Events

Time Frame Day 1 (start of tbo-filgrastim administration) to <= 30 days after the last dose (up to Day 45)
Adverse Event Reporting Description
Arm/Group Title Infants (1 Month to <2 Years) Children (2 to <12 Years) Adolescents (12 to <16 Years)
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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/2 (0%) 0/30 (0%) 0/18 (0%)
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%) 9/30 (30%) 3/18 (16.7%)
Blood and lymphatic system disorders
Anaemia 0/2 (0%) 0 4/30 (13.3%) 5 0/18 (0%) 0
Febrile neutropenia 0/2 (0%) 0 4/30 (13.3%) 6 2/18 (11.1%) 2
Pancytopenia 0/2 (0%) 0 1/30 (3.3%) 1 0/18 (0%) 0
Thrombocytopenia 0/2 (0%) 0 2/30 (6.7%) 2 2/18 (11.1%) 2
Gastrointestinal disorders
Haematemesis 0/2 (0%) 0 1/30 (3.3%) 1 0/18 (0%) 0
Investigations
Alanine aminotransferase increased 0/2 (0%) 0 2/30 (6.7%) 2 1/18 (5.6%) 1
Aspartate aminotransferase increased 0/2 (0%) 0 2/30 (6.7%) 2 1/18 (5.6%) 1
Gamma-glutamyltransferase increased 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 1
Skin and subcutaneous tissue disorders
Hangnail 0/2 (0%) 0 1/30 (3.3%) 1 0/18 (0%) 0
Other (Not Including 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 2/2 (100%) 27/30 (90%) 15/18 (83.3%)
Blood and lymphatic system disorders
Anaemia 1/2 (50%) 1 12/30 (40%) 20 3/18 (16.7%) 3
Febrile neutropenia 1/2 (50%) 1 5/30 (16.7%) 5 0/18 (0%) 0
Leukopenia 2/2 (100%) 2 6/30 (20%) 11 3/18 (16.7%) 3
Lymphopenia 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 3
Neutropenia 2/2 (100%) 6 16/30 (53.3%) 34 9/18 (50%) 16
Thrombocytopenia 2/2 (100%) 5 8/30 (26.7%) 16 4/18 (22.2%) 5
Cardiac disorders
Sinus tachycardia 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 1
Gastrointestinal disorders
Abdominal pain upper 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 2
Abdominal rigidity 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 1
Colitis 1/2 (50%) 1 1/30 (3.3%) 1 0/18 (0%) 0
Constipation 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 1
Diarrhoea 0/2 (0%) 0 2/30 (6.7%) 2 1/18 (5.6%) 2
Enterocolitis 1/2 (50%) 1 0/30 (0%) 0 0/18 (0%) 0
Nausea 0/2 (0%) 0 2/30 (6.7%) 2 2/18 (11.1%) 2
Stomatitis 1/2 (50%) 1 3/30 (10%) 3 2/18 (11.1%) 2
Vomiting 0/2 (0%) 0 5/30 (16.7%) 6 3/18 (16.7%) 6
General disorders
Hyperthermia 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 1
Mucosal inflammation 0/2 (0%) 0 3/30 (10%) 3 3/18 (16.7%) 3
Pyrexia 0/2 (0%) 0 2/30 (6.7%) 2 2/18 (11.1%) 10
Immune system disorders
Hypogammaglobulinaemia 0/2 (0%) 0 0/30 (0%) 0 3/18 (16.7%) 6
Infections and infestations
Cellulitis staphylococcal 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 1
Clostridium difficile colitis 0/2 (0%) 0 1/30 (3.3%) 1 1/18 (5.6%) 2
Oral candidiasis 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 1
Investigations
Alanine aminotransferase increased 0/2 (0%) 0 2/30 (6.7%) 2 0/18 (0%) 0
Aspartate aminotransferase increased 0/2 (0%) 0 2/30 (6.7%) 2 0/18 (0%) 0
Blood lactate dehydrogenase increased 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 1
Gamma-glutamyltransferase increased 0/2 (0%) 0 2/30 (6.7%) 2 0/18 (0%) 0
Neutrophil count decreased 0/2 (0%) 0 2/30 (6.7%) 3 0/18 (0%) 0
White blood cell count decreased 0/2 (0%) 0 2/30 (6.7%) 3 0/18 (0%) 0
Metabolism and nutrition disorders
Decreased appetite 0/2 (0%) 0 2/30 (6.7%) 2 0/18 (0%) 0
Hypoalbuminaemia 0/2 (0%) 0 0/30 (0%) 0 2/18 (11.1%) 4
Hypokalaemia 0/2 (0%) 0 1/30 (3.3%) 1 1/18 (5.6%) 1
Musculoskeletal and connective tissue disorders
Back pain 0/2 (0%) 0 1/30 (3.3%) 1 1/18 (5.6%) 1
Pain in extremity 0/2 (0%) 0 2/30 (6.7%) 2 1/18 (5.6%) 4
Nervous system disorders
Headache 0/2 (0%) 0 1/30 (3.3%) 1 2/18 (11.1%) 2
Neurotoxicity 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 1
Skin and subcutaneous tissue disorders
Rash vesicular 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 1
Skin necrosis 0/2 (0%) 0 0/30 (0%) 0 1/18 (5.6%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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
Email USMedInfo@tevapharm.com
Responsible Party:
Teva Branded Pharmaceutical Products R&D, Inc.
ClinicalTrials.gov Identifier:
NCT02190721
Other Study ID Numbers:
  • XM02-ONC-201
  • 2014-001772-55
First Posted:
Jul 15, 2014
Last Update Posted:
Dec 10, 2021
Last Verified:
Dec 1, 2021