Comparison of Treosulfan-based with Busulfan-based conditioning in paediatric patients with non-malignant diseases
- Conditions
- Male and female children with non-malignant diseases requiring myeloablative conditioning treatment with following allogeneic haematopoietic stem cell transplantation (allo-HSCT) – i.e. primary immunodeficiencies, inborn errors of metabolism, haemoglobinopathies and bone marrow failure syndromes.MedDRA version: 18.0Level: HLTClassification code 10021606Term: Inborn errors of metabolism NECSystem Organ Class: 100000004850MedDRA version: 18.0Level: HLTClassification code 10036700Term: Primary immunodeficiency syndromesSystem Organ Class: 100000004870MedDRA version: 18.0Level: HLTClassification code 10018903Term: Haemoglobinopathies congenitalSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2013-005508-33-IT
- Lead Sponsor
- medac GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 100
1. Non-malignant disease indicated for first myeloablative allogeneic HSCT, including inborn errors of metabolism, primary immunodeficiencies, haemoglobinopathies and bone marrow failure syndromes.
2. First allogeneic HSCT.
3. Available matched sibling donor (MSD), matched family donor (MFD) or matched unrelated donor (MUD). For bone marrow (BM) and peripheral blood (PB) match is defined as at least 9/10 allele matches after four digit typing in human leucocyte antigen (HLA)-A, -B, -C, –DRB1 and DQB1 antigens. For umbilical cord blood (UCB) match is defined as at least 5/6 matches after two digit typing in HLA-A and -B and four digit typing in DRB1 antigens.
4. Age at time of registration from 28 days to less than 18 years of age.
5. Lansky (patients <16 years of age) or Karnofsky (patients = 16 years of age) performance score of at least 70%.
6. Written informed consent of the parents/legal guardians and patient’s assent/consent according to national regulations.
7. Female patients of child-bearing potential or partner of male patients with child-bearing potential must use a highly effective method of contraception (pearl index < 1%) such as complete sexual abstinence, combined oral contraceptive, hormone intrauterine contraceptive device (IUCD), vaginal hormone ring, transdermal contraceptive patch, contraceptive implant or depot contraceptive injection in combination with a second method of contraception like a condom or a cervical cap / diaphragm with spermicide or surgical sterilisation (vasectomy) in male patients or male partners during the study and at least six months thereafter.
8. Negative pregnancy test for females of child-bearing potential.
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
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
1. Second or later HSCT.
2. HSCT from mismatched donor (less than 9/10 BM/peripheral blood stem cells (PBSC) or less than 5/6 matched cord donor).
3. Preterm newborn infants (<37 weeks gestational age) and term newborn infants aged 0 – 27 days at time of registration.
4. Obese paediatric patients with body mass index weight (kg)/[height (m)]² > 30 kg/m².
5. Diagnosis of Fanconi anaemia and other chromosomal breakage disorders, radiosensitivity disorders (deoxyribonucleic acid (DNA) Ligase 4, Cernunnos- X-ray repair cross-complementing protein 4 (XRCC4) like factor (XLF), Nijmegen Breakage Syndrome (NBS)) and Dyskeratosis Congenita.
6. Treatment with cytotoxic drugs within 10 days prior to day 7.
7. Impaired liver function indicated by Bilirubin > three times the upper limit of normal (ULN) or aspartate aminotransferase/alanine aminotransferase (AST/GOT, ALT/GPT) > five times ULN or active infectious hepatitis.
8. Impaired renal function indicated by estimated glomerular filtration rate ([GFR], according to the Schwartz formula) < 60 mL/min/1.73m2.
9. Impaired cardiac function: severe cardiac insufficiency indicated by left ventricular ejection fraction (LVEF) ? 35%.
10. Requirement for supplementary continuous oxygen.
11. Severe active infection requiring deferral of conditioning.
12. Human immunodeficiency virus (HIV) positivity.
13. Severe concomitant illness, comorbidity or condition that would severely limit life expectancy.
14. Known pregnancy, breast feeding.
15. Known hypersensitivity to Treosulfan, Busulfan, Fludarabine and/or Thiotepa.
16. Participation in another interventional clinical study with an experimental drug, within four weeks prior to patient inclusion.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method