E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paediatric Patients Under 6 years of Age with Rhabdomyosarcoma or Wilms’ Tumour on Myelosuppressive Chemotherapy (CmT) Regimen |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10047954 |
E.1.2 | Term | White blood cell disorders |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assess the efficacy of a subcutaneous (SC) dose administration of pegfilgrastim per chemotherapy cycle compared to daily SC dose administrations of filgrastim in children receiving CmT |
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E.2.2 | Secondary objectives of the trial |
Assess the pharmacodynamics, pharmacokinetics, safety, and tolerability including local (injection site) tolerability of a single SC dose administration of pegfilgrastim per chemotherapy cycle compared to daily SC dose administrations of filgrastim in children receiving CmT |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female infants and children from under 6 years of age 2.Children with a pathologically confirmed diagnosis of rhabdomyosarcoma or high-risk Wilms’ tumour, planned for treatment with 1 of the following CmT regimens: • Rhabdomyosarcoma: − Ifosfamide plus vincristine plus actinomycin D (IVA) − Ifosfamide plus vincristine plus actinomycin D plus doxorubicin (IVADo) − Vincristine plus actinomycin D plus cyclophosphamide (VAC) • High-risk Wilms’ tumour: − Cyclophosphamide with doxorubicin and /or etoposide with carboplatin 3. Written informed consent provided by parent(s)/legal representative(s) of the paediatric participant and participant’s assent if able to understand and/or follow study instructions alone or with parental assistance 4. Parents / legally acceptable representative should have signed consent for a CmT regimen that is known to be myelotoxic, with counts expected to drop below an absolute neutrophil count (ANC) of 0.5 × 109/L for at least 3 days. 5. ANC and platelet count: Participants must have an ANC >1 × 109/L and a pl atelet count >100 × 109/L to be eligible for therapy at the start of CmT 6.Normal cardiac, renal, and hepatic function 7.All participants must have a life expectancy of >4 months in the opinion of the investigator 8.On-treatment Eastern Cooperative Oncology Group (ECOG) performance status ≤2 9.Participants with baseline laboratory values acceptable for them to receive chemotherapy |
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E.4 | Principal exclusion criteria |
Any potential participant who meets any of the following criteria will be excluded from participating in the study: 1.Known hypersensitivity to any component of this product. 2.Previous treatment with long-acting G-CSF 3.History of congenital neutropenia or cyclic neutropenia 4.Any illness or condition that in the opinion of the investigator may affect the safety of the participant or the evaluation of any study endpoint 5.Bone marrow involvement 6.Prior bone marrow or stem cell transplant, or prior radiation to ≥25% of bone marrow (e.g., whole pelvic radiation) for any reason, or any therapeutic radiation within the 4 weeks prior to the first dose 7.Ongoing active infection or history of infectious disease within 2 weeks prior to the screening visit 8.A positive polymerase chain reaction test for COVID-19. 9.Treatment with lithium at screening or planned during the study 10.Participation in an interventional clinical study within 30 days or 5 half-lives of the investigational product before enrollment, whichever is longer 11.Participants with autoimmune diseases 12.Participants with severe liver, kidney, heart, or lung dysfunction precluding the expected delivery of the intended chemotherapy regimen |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the efficacy of a single subcutaneous (SC) dose administration of pegfilgrastim per chemotherapy cycle compared to daily SC dose administrations of filgrastim in children receiving CmT |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Incidence and duration of severe neutropenia (ANC <0.5 × 109/L) in each chemotherapy cycle. • Incidence and duration of very severe neutropenia (ANC <0.1 × 109/L) in each chemotherapy cycle. • Incidence of febrile neutropenia (body temperature >38.3°C or 2 consecutive readings higher than 37.8°C measured at the axilla or external ear at least 2 hours apart; and ANC <0.5 × 10^9 /L per chemotherapy cycle and across all chemotherapy cycles. • Area under the curve (AUC) of absolute neutrophil count (AUCANC) in a chemotherapy cycle. ANC nadir (measured in 10^9/L), which is the lowest ANC recorded across all cycles. |
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E.5.2 | Secondary end point(s) |
To assess the pharmacodynamics, pharmacokinetics, safety, and tolerability including local (injection site) tolerability of a single SC dose administration of pegfilgrastim per chemotherapy cycle compared to daily SC dose administrations of filgrastim in children receiving CmT |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Total time (days) in Intensive Care Unit (ICU) across all cycles • Percentage of scheduled chemotherapy dose that was delivered across all cycles • Proportion with chemotherapy doses reduced, omitted, or delayed across all cycles • Time in days in hospital and time in the ICU due to FN or associated infections across all cycles • Number of days of delay of chemotherapy across all cycles • Occurrence and/or resolution of chemotherapy-induced mucositis across all cycles
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Neupogen Singleject (Filgrastim) Solution for injection in a pre-filled syringe 30 MU (0.6 mg/mL) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of last subjects |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |