E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Any paediatric disease with an indication to an allogeneic stem cell transplantation (inclusing leukaemia, primary immunodeficiencies, metabolic disorders and autoimmune or genetic inflammatory bowel disorders). |
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E.1.1.1 | Medical condition in easily understood language |
Any paediatric disease with an indication to an allogeneic stem cell transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
This study aims to describe Treosulfan PK in children and infants undergoing allogeneic stem cell transplantation and to determine if this is a significant variable in determining transplant outcome.
The primary objective of the study is:
1) Assess PK parameters such as Cmax, t1/2 and AUC0-∞ after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.
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E.2.2 | Secondary objectives of the trial |
These are the secondary objectives of this study:
1) Assess interindividual and intraindividual variability of PK parameters in children of different age and weight; 2) Assess the relationship between PK parameters and patient characteristics; 3) Assess the relationship between Treosulfan PK and regimen related toxicity (using the NCI toxicity criteria scoring system) and survival; 4) Assess the relationship between Treosulfan PK and efficacy parameters, such as rate of engraftment and donor chimerism
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients affected by malignant or non-malignant diseases with an indication to allogeneic HSCT. Patients must meet all of the following criteria for admission in the study:
1) age ≥ 28 days and ≤ 18 years old; 2) Karnofsky Performance Status ≥ 50 or Lansky Performance Status ≥ 30; 3) provide signed, written informed consent from parent or guardian; 4) be able to comply with study procedures and follow-up examinations; 5) have adequate organ function (as indicated by Table 1, page 27), within 14 days prior enrollment; 6) negative pregnancy test in post-pubertal female patients.
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded from study admission:
1) Patients aged < 28 days and > 18 years old; 2) patients with compromised organ function*; 3) patients with any other severe concurrent disease, which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study; 4) Known hypersensitivity to Treosulfan or Fludarabine; 5) Pregnancy/lactation.
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E.5 End points |
E.5.1 | Primary end point(s) |
Analyze Cmax, t1/2 and AUC0-∞ of Treosulfan with serial blood tests; |
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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) |
1) Assess the incidence of grade III-IV adverse events (NCI common toxicity criteria, version 4.0) within the first 100 days after transplant; 2) Assess transplant related mortality at 100 days after transplant; 3) Assess cumulative incidence and severity of acute GvHD 4) Assess the timing of neutrophil and platelet recovery; 5) Assess donor engraftment in different cell lineages (myeloid and lymphoid) at 30, 60, 90, 180 and 360 days after transplant; 6) Assess overall survival and disease-free survival at 1 year post transplant
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
first 100 days after transplant,Assess donor engraftment in different cell lineages (myeloid and lymphoid) at 30, 60, 90, 180 and 360 days after transplant,follow up at 1 year |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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Recruitment into the trial will stop on 28.02.2017 but patients will remain under followup (for data collection)until one year post HSCT (last visit as part of the protocol in 2017).Study will be cloased after the last patient completes 1 year follow up |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 31 |