Clinical trial comparing Lipegfilgrastim to Filgrastim in Pediatric Patients Diagnosed with Ewing Family of Tumors or Rhabdomyosarcoma Receiving Chemotherapy.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2015-000087-34-HU
• Date of registration: 22/04/2015
• Prospective Registration: Yes
• Primary sponsor: Merckle GmbH
• Public title: Clinical trial comparing Lipegfilgrastim to Filgrastim in Pediatric Patients Diagnosed with Ewing Family of Tumors or Rhabdomyosarcoma Receiving Chemotherapy.
• Scientific title: An Open-Label, Randomized, Active-Controlled, Multicenter Study to Evaluate the Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of Lipegfilgrastim 100 µg/kg Body Weight in Comparison to Filgrastim 5 µg/kg Body Weight in Pediatric Patients Diagnosed with Ewing Family of Tumors or Rhabdomyosarcoma Receiving Chemotherapy
• Date of first enrolment: 05/06/2015
• Target sample size: 42
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000087-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Bulgaria, Croatia, Czech Republic, Germany, Hungary, Lithuania, Poland, Romania, Russian Federation, Slovakia, Spain, Ukraine

Contacts

• Name: Dr. med. Andreas Lammerich
• Affiliation: Merckle GmbH

• Name: Dr. med. Andreas Lammerich
• Affiliation: Merckle GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
a. Male or female children and adolescents aged 2 to <18 years at screening.
b. Written informed consent provided by parent(s)/legal representative(s) of the pediatric patient and patient’s assent if appropriate, before screening procedures are initiated.
c. Able to understand and/or follow study instructions alone or with parental assistance.
d. Diagnosed with the Ewing family of tumors, or rhabdomyosarcoma.
e. Scheduled to receive 1 of the following CTX regimens (inpatient or outpatient):
For the Ewing Family of Tumors:
- Vincristine/Ifosfamide/Doxorubicin/Etoposide (VIDE); with concomitant sodium 2-mercaptoethane sulfonate (MESNA) according to local standards.
- Vincristine/Doxorubicin/Cyclophosphamide alternating with Ifosfamide/Etoposide (VDC/IE); with concomitant MESNA treatment according to local standards.
- Vincristine/Actinomycin/Cyclophosphamide (VAC); with concomitant MESNA treatment according to local standards.
For Rhabdomyosarcoma:
VAC; with concomitant MESNA treatment according to locals standards.
- VDC/IE; with concomitant MESNA treatment according to local standards.
- Ifosfamide, Vincristine, and Actinomycin D (IVA); with concomitant MESNA treatment according to local standards.
-Ifosfamide, Vincristine and Actinomycin D (IVA); with concomitant MESNA treatment according to local standards.
f. Minimum BW 12.5 kg.
g. Life expectancy of at least 3 months with appropriate therapy.
h. White blood cell (WBC) count >2.5 × 10^9/L, absolute neutrophil count (ANC) =1.5 × 10^9/L, and platelet count =100 × 10^9/L (at screening and prior to CTX).
i. For patients aged =12 years, Eastern Cooperative Oncology Group (ECOG) performance status =2.
j. Fertile patients (male or female) must use highly reliable contraceptive measures for the entire duration of the study.
k. Female patients who have attained menarche must have a negative urine pregnancy test at the screening visit.
Are the trial subjects under 18? yes
Number of subjects for this age range: 42
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
a. Previous exposure to filgrastim, pegfilgrastim, lenograstim or other granulocyte colony stimulating factors (G-CSFs) / granulocyte macrophage colony-stimulating factors (GM-CSFs) in clinical development within 6 weeks prior to the first lipegfilgrastim/filgrastim administration in this study.
b. Known hypersensitivity to filgrastim, pegfilgrastim, lenograstim, any other G-CSF in clinical development or any LONQUEX (lipegfilgrastim) excipients.
c. History of congenital neutropenia or cyclic neutropenia.
d. Patients with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation, as determined by medical history, physical examinations, electrocardiogram (ECG), laboratory tests, or imaging.
e. Pregnancy or breast feeding (if a patient becomes pregnant during the study she will be withdrawn from the study).
f. Prior bone marrow or stem cell transplant, or prior radiation to =25% of bone marrow (eg, whole pelvic radiation) for any reason, or any therapeutic radiation within the 3 weeks prior to the first dose of study drug (lipegfilgrastim/filgrastim).
g. Major surgery or serious infection within 3weeks before first administration of study drug (lipegfilgrastim/filgrastim), serious trauma or compound medical procedure within the 4 weeks prior to the first study drug dose.
h. Treatment with lithium at screening or planned during the study.
i. Participation in a clinical study with an investigational product within
30 days or 5 half-lives before randomization, whichever is longer.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Neutropenia in pediatric patients diagnosed with Ewing family of Tumors or rhabdomyosarcoma receiving chemotherapy
MedDRA version: 19.0 Level: PT Classification code 10029354 Term: Neutropenia System Organ Class: 10005329 - Blood and lymphatic system disorders
MedDRA version: 19.0 Level: PT Classification code 10016288 Term: Febrile neutropenia System Organ Class: 10005329 - Blood and lymphatic system disorders

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: LONQUEX
Product Name: Lipegfilgrastim
Product Code: XM22
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Lipefilgrastim
CAS Number: 1117844-87-7
Current Sponsor code: XM22
Other descriptive name: glyco-PEGylated r-metHuG-CSF
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Neupogen 30 MU (0.3 mg/ml) solution for injection
Product Name: Neupogen
Pharmaceutical Form: Solution for injection
INN or Proposed INN: FILGRASTIM
CAS Number: 121181-53-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.3-

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint is the duration of severe neutropenia (DSN) in cycle 1, defined as the number of days with severe neutropenia in cycle 1 (from start of CTX until day 15). Severe neutropenia is defined as grade 4 neutropenia, with ANC <0.5 × 10^9/L.

Timepoint(s) of evaluation of this end point: Samples for ANC assessments in cycles 1 to 4 will be obtained on day 1 prior to study drug administration, on days 2, 4, 5, 6, 7, 8, 9, 10, 12, and 15 and at EOS/(or ET) visit.

Main Objective: The primary objective of this study is to assess the efficacy of a single subcutaneous (sc) dose of 100 µg/kg body weight (BW) of lipegfilgrastim per cycle compared to daily 5 µg/kg BW of filgrastim doses in children receiving CTX

Secondary Objective: The secondary objectives of this study are to assess pharmacodynamics, pharmacokinetics, safety, tolerability, and immunogenicity of a single sc dose of 100 µg/kg BW of lipegfilgrastim per cycle compared to daily doses of 5 µg/kg BW of filgrastim.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Samples for PD assessments (ANC) in cycles 1 to 4 will be obtained on day 1 prior to study drug administration, on days 2, 4, 5, 6, 7, 8, 9, 10, 12, and 15 and at EOS/(or ET) visit.

Continous tempareture measurements during the days 1-21 of each cycle.

Secondary end point(s): Secondary Efficacy Variables and Endpoints:
The secondary efficacy endpoints for this study are as follows:
- Incidence of severe neutropenia (ANC <0.5 × 10^9/L) in each cycle (1-4).
- Incidence of very severe neutropenia (ANC <0.1 × 10^9/L) in each cycle (1-4).
- Incidence of febrile neutropenia (FN) (defined as body temperature >38.3°C or 2 consecutive readings higher than 37.8°C measured at axilla or external ear for 2 hours and ANC <0.5 × 10^9/L or expected to fall below 0.5 × 10^9/L) per cycle and across all cycles.
- DSN in cycles 2-4 per cycle.
- Duration of very severe neutropenia in cycles 1-4 per cycle.
Efficacy evaluations will be performed on blood samples taken for the pharmacodynamic assessments in combination with temperature measurements.

Secondary Pharmacodynamic Variables and Endpoints:
- Area under the curve of ANC (AUCANC) until day 15 in cycle 1.
- ANC nadir, ie, the lowest ANC value recorded, per cycle.
- Time to ANC nadir per cycle, defined as the time from start of CTX until occurrence of the ANC nadir in the cycle.
- Time to ANC nadir per cycle, defined as the time from first study drug administration in a cycle until occurrence of the ANC nadir in the cycle.
- Time to ANC recovery (ANC >1.0 × 10^9/L and ANC >2.0 × 10^9/L) from first day of CTX.
- Time to ANC recovery (ANC >1.0 × 10^9/L and ANC >2.0 × 10^9/L) from nadir per cycle.

Secondary ID(s)

XM22-08

Source(s) of Monetary Support

Merckle GmbH

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 19/07/2019
• Date Completed: 08/01/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000087-34/results