E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paediatric cancer patients (aged 1 to <18 years) with Ewing’s sarcoma/soft tissue sarcoma, lymphoma, neuroblastoma and all other malignancies (excluding leukaemia) who are planned to undergo high dose chemotherapy followed by autologous haematopoietic stem cell transplantation (HSCT) rescue |
Ewing szarkómás/lágyrész-szarkómás, limfómás, neuroblasztómás és minden egyéb rosszindulatú daganatos betegségben (de a leukémiát kizárva) szenvedő, 1 éves kort betöltött, de 18. életévét még nem elért gyermek, akinél nagydózisú kemoterápiát terveznek rákövetkező autológ hemopoetikus őssejttranszplantációs terápiával. |
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E.1.1.1 | Medical condition in easily understood language |
Solid tumours (excluding leukaemia) which will be treated with high dose chemotherapy followed by transplantation of the child's own stem cells. |
Szolid tumorok (kivéve a leukémiát), amelyet nagydózisú kemoterápiával, majd ezt követően a gyermek saját őssejtjeit felhasználó transzplantációs terápiával fognak kezelni. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to confirm the appropriate dose and efficacy, and to characterise the safety, pharmacokinetics and pharmacodynamics of plerixafor across age and size in paediatric cancer patients when given in addition to standard mobilisation of HSCs into peripheral blood. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to confirm the efficacy and safety of plerixafor in addition to standard mobilisation of HSCs into peripheral blood, and subsequent collection by apheresis, in paediatric cancer patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 1 to <18 years
2. Ewing’s sarcoma, soft tissue sarcoma, lymphoma, neuroblastoma, or other malignancy including brain tumours
(excluding any form of leukaemia) requiring treatment with high dose chemotherapy and autologous transplant as rescue therapy
3. Eligible for autologous transplantation
4. Recovered from all acute significant toxic effects of prior chemotherapy
5. Adequate performance status
– for patients ≥16 years of age, defined as Karnofsky score >60
– for patients <16 years of age, defined as Lansky score >60
6. Absolute neutrophil count >0.75 × 10P9/L
7. Platelet count >50 × 10P9/L
8. Calculated creatinine clearance (using the Schwartz method):
– during study Stage 2, >60 mL/min/1.73mP2
9. Liver functions <3 × upper limit of normal :
Aspartate aminotransferase/serum glutamic oxaloacetic transaminase
(AST/SGOT), alanine aminotransferase/serum glutamic pyruvic transaminase
(ALT/SGPT) and total bilirubin
10. The patient and/or their parent/legal guardian is willing and able to provide signed informed consent
11. Patients who are sexually active must be willing to abstain from sexual intercourse or agree to use an approved form of contraception while receiving plerixafor and/or standard mobilisation treatment and for at least 3 months following any plerixafor treatment. |
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E.4 | Principal exclusion criteria |
1. Any form of leukaemia
2. A co-morbid condition, such as ventricular arrhythmias, which, in the view of the Investigator, renders the patient
at high-risk from treatment complications
3. Previous stem cell transplantation
4. Patients with persistent high percentage marrow involvement prior to mobilisation will be prohibited.
5. On-going toxicities (excluding alopecia) Grade ≥2 resulting from prior chemotherapy
6. Acute infection
7. Fever (temperature >38.5°C) - if fever is between 37°C and 38.5°C, infection must be excluded as a cause
8. Known HIV seropositivity, AIDS, hepatitis C or active hepatitis B infections.
9. Positive pregnancy test in post pubertal girls
10. History of clinically significant cardiac abnormality or arrhythmia
11. Use of an investigational drug which is not approved in any indication either in
adults or paediatrics within 2 weeks prior to the first dose of G-CSF to be administered as part of the patient’s planned standard mobilisation regimen, and/or during the study up until engraftment of the transplant. If patients are on
investigational drugs as part of their anti-cancer regimen, this should be discussed with the Sponsor before screening. Drugs approved for other indications that are being used in a manner considered standard of care for this transplant procedure are allowed
12. The patient (and/or their parent/legal guardian), in the opinion of the Investigator,
is unable to adhere to the requirements of the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the difference between the 2 treatment arms in Stage 2 (comparative part of the study) in the proportion of patients achieving at least a doubling of peripheral blood CD34+ count from the morning of the day preceding the first apheresis day to the morning prior to apheresis. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Number of days of apheresis required to reach ≥2 × 10^6 CD34+ cells/kg [ Time Frame: Up to 5 days ] During Stage 1 and Stage 2
•Yield of CD34+ cells for each apheresis [ Time Frame: Up to 5 days ]
During Stage 1 and Stage 2
•Total CD34+ cell yield [ Time Frame: Up to 5 days ] During Stage 1 and Stage 2
•Percentage of patients proceeding to transplant [ Time Frame: Within 6 months of last apheresis ] During Stage 1 and Stage 2
•Percentage of patients successfully engrafting [ Time Frame: 3, 6, 12 and 24 months post-transplant ] During Stage 1 and Stage 2
•Percentage of patients with durable engraftment [ Time Frame: 3, 6, 12 and 24 months post-transplant ] During Stage 1 and Stage 2
•Summary of adverse events (AEs) [ Time Frame: Up to 24 months after last transplant or 24 months after last dose (for patients that do not transplant within 6 months of last apheresis) ] During Stage 1 and Stage
2
•Duration of hospitalizations (planned or unplanned) [ Time Frame: Throughout the duration of the study ] During Stage 1 and Stage 2
•Mobilization of tumor cells into peripheral blood [ Time Frame: Up to 5 days ] During Stage 1 and Stage 2
•Relapse rates [ Time Frame: 3, 6, 12 and 24 months post-transplant ]
During Stage 1 and Stage 2
•Occurrence of secondary malignancies [ Time Frame: 3, 6, 12 and 24 months post-transplant ] During Stage 1 and Stage 2
•Incidence of primary and secondary graft failure [ Time Frame: 3, 6, 12 and 24 months post-transplant ] During Stage 1 and Stage 2
•Time to secondary graft failure [ Time Frame: Up to 24 months posttransplant] During Stage 1 and Stage 2
•Survival rates [ Time Frame: 3, 6, 12 and 24 months post-transplant ]
During Stage 1 and Stage 2 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Stage 1 only: dose ranging |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Stage 1 only: dose ranging - Stage 1 completed |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Csak a vizsgálat 2. szakasza: összehasonlító, randomizált vizsgálat |
Stage 2 only: a comparative randomised study |
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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 |
Csak a vizsgálat 2. szakasza: standard mobilizációs kezelés |
Stage 2 only: standard mobilisation treatment |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Czech Republic |
Denmark |
France |
Germany |
Hungary |
Israel |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |