Clinical Trial Results:
An Open Label, Randomized, Active Controlled, Multicenter Study to Evaluate the Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of Lipegfilgrastim 100 mcg/kg Body Weight in Comparison to Filgrastim 5 mcg/kg Body Weight in Pediatric Patients Diagnosed With Ewing Family of Tumors or Rhabdomyosarcoma Receiving Chemotherapy
Summary
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EudraCT number |
2015-000087-34 |
Trial protocol |
HU LT SK CZ BG DE ES RO PL BE HR |
Global end of trial date |
08 Jan 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Jul 2019
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First version publication date |
19 Jul 2019
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
XM22-08
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Merckle GmbH, Teva Pharmaceutical Industries
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Sponsor organisation address |
Ludwig-Merckle-Strasse 3, Blaubeuren, Germany, D-89143
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Public contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc, 001 2155913000, info.eraclinical@teva.de
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Scientific contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc, 001 2155913000, info.eraclinical@teva.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001019-PIP01-10 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Jan 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Jan 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the efficacy of a single subcutaneous (SC) dose of 100 micrograms per kilogram (mcg/kg) body weight (BW) of lipegfilgrastim per cycle compared to daily SC doses of 5 mcg/kg BW of filgrastim in children receiving cytotoxic chemotherapy (CTX).
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Protection of trial subjects |
This study was conducted in full accordance with the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6), and any applicable national and local laws and regulations (for example, Code of Federal Regulations Title 21, Parts 11, 50, 54, 56, 312, and 314; European Union Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of GCP in the conduct of clinical trials on medicinal products for human use).
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Background therapy |
CTX regimens were administered intravenously (IV) every 3 weeks for 4 cycles. It comprised: • IVA (Used in Rhabdomyosarcoma): ifosfamide 3 grams per square meter (g/m^2) on Day 1,2 of each cycle + vincristine 1.5 mg/m^2 on Day 1,8,15 of each cycle + actinomycin D 1.5 mg/m^2 on Day 1 of each cycle; • VAC (Used in Ewing family of tumors rhabdomyosarcoma): vincristine 1.5 mg/m^2 on Day 1,8,15 of each cycle + actinomycin D 0.015 milligrams per kilogram per day (mg/kg/day) for 5 days or 1.5 mg/m^2 every 3 weeks + cyclophosphamide 1.2-2.2 g/m^2/day for 1 to 3 days starting on Day 1 of each cycle; • IVADo (Used in Rhabdomyosarcoma): ifosfamide 3.0 g/m^2 on Day 1,2 of each cycle + vincristine 1.5 mg/m^2 on Day 1, and weekly, for a total of 7 consecutive doses until Week 7, + actinomycin D 1.5 mg/ m^2 on Day 1 of each cycle + doxorubicin 30.0 mg/m^2 on Day 1,2 of each cycle; • VDC/IE (Used in Ewing family of tumors rhabdomyosarcoma): vincristine 2 mg/m^2 on Day 1,8,15 of Cycles 1 and 3 + doxorubicin 75.0 mg/m^2 on Day 1of Cycles 1 and 3 + cyclophosphamide 1200 mg/m^2 on Day 1, 2 of Cycles 1 and 3 alternating with ifosfamide 1800 mg/m^2/day for 5 days in Cycles 2 and 4 + etoposide 100 mg/m^2/day for 5 days in Cycles 2 and 4; • VIDE (Used in Ewing family of tumors): vincristine 1.5 mg/m^2 on Day 1 of each cycle + ifosfamide 3.0 g/m^2 on Day 1, 2, 3 of each cycle + doxorubicin 20 mg/m^2 on Day 1, 2, 3 of each cycle + etoposide 150 mg/m^2 on Day 1, 2, 3 of each cycle. Study Day 1 corresponding in different CTX regimens was calculated as: 1 day after end of CTX in week 1 of a cycle. Day 1 corresponds for VDC/IE CTX regimen: to CTX-day 2+1 during cycles 1 and 3, and to CTX day 5+1 during cycles 2 and 4; for VIDE CTX regimen: to CTX-day 3+1; for VAC CTX regimen: to CTX-day 1+1, CTX-day 2+1, CTX-day 3+1 or CTX-day 5+1 (depending on actinomycin schedule and number of days cyclophosphamide was given); for IVA CTX regimens: to CTX-day 2+1; for IVADo CTX regimen: to: CTX-day 2+1. | ||
Evidence for comparator |
Pegfilgrastim is not approved for children, therefore filgrastim is the comparator in this study. | ||
Actual start date of recruitment |
08 Sep 2015
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
9 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Russian Federation: 16
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Country: Number of subjects enrolled |
Ukraine: 12
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Country: Number of subjects enrolled |
Belarus: 3
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Country: Number of subjects enrolled |
Romania: 3
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Country: Number of subjects enrolled |
Czech Republic: 2
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Country: Number of subjects enrolled |
Slovakia: 2
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Country: Number of subjects enrolled |
Croatia: 1
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Country: Number of subjects enrolled |
Georgia: 1
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Country: Number of subjects enrolled |
Hungary: 1
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Country: Number of subjects enrolled |
Spain: 1
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Worldwide total number of subjects |
42
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EEA total number of subjects |
10
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
28
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Adolescents (12-17 years) |
14
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 45 participants were screened, of which 43 were enrolled and 42 were randomized in 1:1 ratio to lipegfilgrastim or filgrastim. 1 participant was enrolled but not randomized as the youngest age cohort (2 to less than [<] 6 years) was not started at time of enrollment. 2 participants were screen failure due to eligibility criteria not met. | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Lipegfilgrastim | ||||||||||||||||||||||||
Arm description |
Participants received a single SC dose of lipegfilgrastim (100 mcg/kg BW; maximum 6 milligrams [mg]) approximately 24 hours (+6 hours) after end of the last CTX in Week 1 of the specific regimen for a total of 4 CTX cycles; and CTX regimen IV every 3 weeks of each CTX cycle over 4 CTX cycles (each cycle=21 days). | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
LONQUEX
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Lipegfilgrastim 100 mcg/kg BW single dose was administered as per the schedule specified in the respective arm.
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Arm title
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Filgrastim | ||||||||||||||||||||||||
Arm description |
Participants received filgrastim 5 mcg/kg BW SC injection once daily (approximately 24 hours [+6 hours] after end of the last CTX in Week 1 of the specific regimen) for at least 5 consecutive days or until absolute neutrophil count (ANC) had returned to greater than or equal to (>=) 2*10^9 per liter for each CTX cycle up to 4 cycles (maximum period of filgrastim administration was 14 days). Where ANC greater than (>) 2*10^9 per liter before the end of the expected nadir, dosing was continued until the expected nadir at the discretion of the Investigator. CTX regimen was administered IV every 3 weeks of each CTX cycle over 4 CTX cycles (each cycle=21 days). | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
NEUPOGEN
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Filgrastim 5 mcg/kg BW was administered as per the schedule specified in the respective arm.
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Baseline characteristics reporting groups
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Reporting group title |
Lipegfilgrastim
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Reporting group description |
Participants received a single SC dose of lipegfilgrastim (100 mcg/kg BW; maximum 6 milligrams [mg]) approximately 24 hours (+6 hours) after end of the last CTX in Week 1 of the specific regimen for a total of 4 CTX cycles; and CTX regimen IV every 3 weeks of each CTX cycle over 4 CTX cycles (each cycle=21 days). | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Filgrastim
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Reporting group description |
Participants received filgrastim 5 mcg/kg BW SC injection once daily (approximately 24 hours [+6 hours] after end of the last CTX in Week 1 of the specific regimen) for at least 5 consecutive days or until absolute neutrophil count (ANC) had returned to greater than or equal to (>=) 2*10^9 per liter for each CTX cycle up to 4 cycles (maximum period of filgrastim administration was 14 days). Where ANC greater than (>) 2*10^9 per liter before the end of the expected nadir, dosing was continued until the expected nadir at the discretion of the Investigator. CTX regimen was administered IV every 3 weeks of each CTX cycle over 4 CTX cycles (each cycle=21 days). | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lipegfilgrastim
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Reporting group description |
Participants received a single SC dose of lipegfilgrastim (100 mcg/kg BW; maximum 6 milligrams [mg]) approximately 24 hours (+6 hours) after end of the last CTX in Week 1 of the specific regimen for a total of 4 CTX cycles; and CTX regimen IV every 3 weeks of each CTX cycle over 4 CTX cycles (each cycle=21 days). | ||
Reporting group title |
Filgrastim
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Reporting group description |
Participants received filgrastim 5 mcg/kg BW SC injection once daily (approximately 24 hours [+6 hours] after end of the last CTX in Week 1 of the specific regimen) for at least 5 consecutive days or until absolute neutrophil count (ANC) had returned to greater than or equal to (>=) 2*10^9 per liter for each CTX cycle up to 4 cycles (maximum period of filgrastim administration was 14 days). Where ANC greater than (>) 2*10^9 per liter before the end of the expected nadir, dosing was continued until the expected nadir at the discretion of the Investigator. CTX regimen was administered IV every 3 weeks of each CTX cycle over 4 CTX cycles (each cycle=21 days). |
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End point title |
Duration of Severe Neutropenia (DSN) in Cycle 1 | ||||||||||||
End point description |
DSN was defined as the number of days with severe neutropenia in Cycle 1 (from start of CTX until Day 15). Severe neutropenia was defined as Grade 4 neutropenia with ANC less than (<) 0.5 * 10^9 per liter. If the ANC was >0.5 * 10^9 per liter, DSN was set to 0. Per-Protocol (PP) analysis set included all randomized participants for whom no protocol violations were reported that may have impacted the efficacy of the investigational medicinal product (IMP).
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End point type |
Primary
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End point timeframe |
From start of CTX until Day 15 of Cycle 1
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Statistical analysis title |
Lipegfilgrastim versus Filgrastim | ||||||||||||
Statistical analysis description |
A Poisson regression with identity link was used with factors of treatment and age group, and baseline (before IMP administration) ANC value as covariate.
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Comparison groups |
Lipegfilgrastim v Filgrastim
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
P-value |
= 0.102 [2] | ||||||||||||
Method |
Poisson analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
1
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.21 | ||||||||||||
upper limit |
2.26 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.61
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Notes [1] - There was no hypothesis testing as the study was not powered. [2] - p-value is reported for the treatment difference. |
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End point title |
Number of Participants With Severe Neutropenia and Very Severe Neutropenia | |||||||||||||||||||||||||||||||||
End point description |
Severe neutropenia was defined as Grade 4 neutropenia with ANC <0.5 * 10^9 per liter. Very severe neutropenia was defined as ANC <0.1 * 10^9 per liter. PP analysis set included all randomized participants for whom no protocol violations were reported that may have impacted the efficacy of the IMP. Here, 'n' signifies number of participants analyzed for specified categories.
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End point type |
Secondary
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End point timeframe |
Cycles 1, 2, 3, and 4 (each cycle=21 days)
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No statistical analyses for this end point |
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End point title |
Number of Participants With Febrile Neutropenia (FN) | ||||||||||||||||||||||||
End point description |
FN was defined as an axillary or external ear temperature greater than (>) 38.3 degrees centigrade or 2 consecutive readings >37.8 degrees centigrade for 2 hours (2 consecutive readings at least 2 hours apart) and ANC<0.5 * 10^9 per liter or expected to be <0.5 * 10^9 per liter per cycle and across all cycles. PP analysis set included all randomized participants for whom no protocol violations were reported that may have impacted the efficacy of the IMP. Here, 'n' signifies number of participants analyzed for specified categories.
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End point type |
Secondary
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End point timeframe |
Cycles 1, 2, 3, and 4 (each cycle = 21 days)
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No statistical analyses for this end point |
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End point title |
DSN in Cycles 2 to 4 Per Cycle | |||||||||||||||||||||
End point description |
DSN was defined as the number of days with severe neutropenia in Cycle 1 (from start of CTX until Day 15). Severe neutropenia was defined as Grade 4 neutropenia with ANC <0.5 * 10^9 per liter. If the ANC was >0.5 * 10^9 per liter, DSN was set to 0. PP analysis set included all randomized participants for whom no protocol violations were reported that may have impacted the efficacy of the IMP. Here, 'n' signifies number of participants analyzed for specified categories.
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End point type |
Secondary
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End point timeframe |
Cycles 2, 3, and 4
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No statistical analyses for this end point |
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End point title |
Duration of Very Severe Neutropenia | ||||||||||||||||||||||||
End point description |
Very severe neutropenia was defined as ANC <0.1 * 10^9 per liter. It was set to 0, if ANC was <0.1 * 10^9 per liter. PP analysis set included all randomized participants for whom no protocol violations were reported that may have impacted the efficacy of the IMP. Here, 'n' signifies number of participants analyzed for specified categories.
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End point type |
Secondary
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End point timeframe |
Cycle 1, 2, 3, and 4 (each cycle =21 days)
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No statistical analyses for this end point |
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End point title |
Area Under the Curve of ANC (AUCANC) | ||||||||||||
End point description |
Calculation of AUCANC was performed by linear trapezoid rule. Missing ANC values were not imputed. PP analysis set included all randomized participants for whom no protocol violations were reported that may have impacted the efficacy of the IMP.
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End point type |
Secondary
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End point timeframe |
Day 1 to Day 15 in Cycle 1 (Cycle length = 21 days)
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No statistical analyses for this end point |
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End point title |
ANC Nadir: the Lowest ANC Value Recorded | ||||||||||||||||||||||||
End point description |
PP analysis set included all randomized participants for whom no protocol violations were reported that may have impacted the efficacy of the IMP. Here, 'n' signifies number of participants analyzed for specified categories.
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End point type |
Secondary
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End point timeframe |
Cycle 1, 2, 3, and 4 (each cycle =21 days)
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No statistical analyses for this end point |
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End point title |
Time to ANC Nadir From Start of CTX | ||||||||||||||||||||||||
End point description |
Time to ANC nadir was defined as the time from start of CTX until occurrence of the ANC nadir in the cycle. PP analysis set included all randomized participants for whom no protocol violations were reported that may have impacted the efficacy of the IMP. Here, 'n' signifies number of participants analyzed for specified categories.
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End point type |
Secondary
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End point timeframe |
Cycle 1, 2, 3, and 4 (each cycle =21 days)
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No statistical analyses for this end point |
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End point title |
Time to ANC Nadir From First IMP Administration | ||||||||||||||||||||||||
End point description |
Time to ANC nadir was defined as the time from first IMP administration in a cycle until occurrence of the ANC nadir in the cycle. PP analysis set included all randomized participants for whom no protocol violations were reported that may have impacted the efficacy of the IMP. Here, 'n' signifies number of participants analyzed for specified categories.
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End point type |
Secondary
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End point timeframe |
Cycle 1, 2, 3, and 4 (each cycle = 21 days)
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No statistical analyses for this end point |
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End point title |
Time to ANC Recovery From First Day of CTX | ||||||||||||||||||||||||||||||||||||
End point description |
Time to ANC recovery at threshold of ANC >1.0 * 10^9 per liter and >2.0 * 10^9 per liter are reported. PP analysis set included all randomized participants for whom no protocol violations were reported that may have impacted the efficacy of the IMP. Here, 'n' signifies number of participants analyzed for specified categories.
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End point type |
Secondary
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End point timeframe |
Cycle 1, 2, 3, and 4 (each cycle =21 days)
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No statistical analyses for this end point |
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End point title |
Time to ANC Recovery From Nadir | ||||||||||||||||||||||||||||||||||||
End point description |
Time to ANC recovery at threshold of ANC >1.0 * 10^9 per liter and >2.0 * 10^9 per liter are reported. PP analysis set included all randomized participants for whom no protocol violations were reported that may have impacted the efficacy of the IMP. Here, 'n' signifies number of participants analyzed for specified categories.
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End point type |
Secondary
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End point timeframe |
Cycle 1, 2, 3, and 4 (each cycle = 21 days)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From start of study drug administration (Day 1) up to end of follow-up (Day 365)
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Adverse event reporting additional description |
Safety analysis set included all randomized participants who received at least 1 dose of IMP.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Filgrastim
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Reporting group description |
Participants received filgrastim 5 mcg/kg BW SC injection once daily (approximately 24 hours [+6 hours] after end of the last CTX in Week 1 of the specific regimen) for at least 5 consecutive days or until ANC had returned to >=2*10^9 per liter for each CTX cycle up to 4 cycles (maximum period of filgrastim administration was 14 days). Where ANC >2*10^9 per liter before the end of the expected nadir, dosing was continued until the expected nadir at the discretion of the Investigator. CTX regimen was administered IV every 3 weeks of each CTX cycle over 4 CTX cycles (each cycle=21 days). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lipegfilgrastim
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Reporting group description |
Participants received a single SC dose of lipegfilgrastim (100 mcg/kg BW; maximum 6 mg) approximately 24 hours (+6 hours) after end of the last CTX in Week 1 of the specific regimen for a total of 4 CTX cycles; and CTX regimen IV every 3 weeks of each CTX cycle over 4 CTX cycles (each cycle=21 days). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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02 Feb 2016 |
The following major procedural changes (not all-inclusive) were made to the protocol:
a) Introduce additional permitted on-study CTX regimens, VAC, for participants with Ewing family of tumors, and IVADo (ifosfamide plus vincristine plus actinomycin plus doxorubicin) for participants with rhabdomyosarcoma. These changes are aligned with the European Medicine Agency decision (EMA/773335/2015, dated 21 December 2015) on the acceptance of modification of the agreed upon pediatric investigational plan for lipegfilgrastim (EMEA-001019-PIP01-10_M03).
- Indicate that lipegfilgrastim will be administered on CTX-Day 2+1 for the IVADo regimen.
- Indicate that CTX Dn, the last day of the CTX in week 1 of a cycle for the IVADo regimen is Day 2.
- Indicate that study Day 1, which is the day after end of CTX in Week 1 of a cycle for IVADo regimen is CTX-Day 2+1.
b) Indicate that the maximum allowable dose of vincristine is per local standards for VIDE, VDC/IE, and VAC regimens. Specify CTX regimen by cancer type. Indicate that the maximum allowable dose of actinomycin is per local standards for IVA.
c) Modify the description of the IMP to comply with the product specification.
d) Modify the adverse drug reaction profile with respect to the incidence of splenomegaly to align with forthcoming changes to the Summary of Product Characteristics.
e) Clarify that the Investigator may use test results from local laboratories (as part of routine medical care) at screening to initiate CTX and check inclusion and exclusion criteria only in exceptional medical situations, should the results from the central laboratory for the clinical study not be available.
f) Clarify exclusion criteria to indicate participation in a clinical study “with an IMP” within 30 days or “5 half-lives” before randomization, whichever is longer. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
None reported |