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Clinical study to examine the safety and efficacy of Treosulfan used as part of a conditioning therapy prior to a stem cell transplantation in children with blood cancer.

Phase 1
Conditions
Male and female children with haematologic malignant diseases as acute lymphoblastic leukaemias (ALL), acute myeloid leukaemias (AML), myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukaemias (JMML), requiring myeloablative conditioning treatment with following allogeneic haematopoietic stem cell transplantation (allo-HSCT)
MedDRA version: 18.0Level: LLTClassification code 10054439Term: Juvenile chronic myelomonocytic leukemiaSystem Organ Class: 100000004864
MedDRA version: 18.0Level: LLTClassification code 10060355Term: Acute myeloid leukaemia in remissionSystem Organ Class: 100000004864
MedDRA version: 18.0Level: LLTClassification code 10028534Term: Myelodysplastic syndrome NOSSystem Organ Class: 100000004864
MedDRA version: 18.0Level: LLTClassification code 10000844Term: Acute lymphoblastic leukaemiaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
Registration Number
EUCTR2013-003604-39-IT
Lead Sponsor
medac GmbH
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
70
Inclusion Criteria

1. Haematologic malignant disease i.e. ALL, AML, MDS or JMML, indicated for allo-HSCT.
2.Indication for first allo-HSCT or second allo-HSCT due to disease relapse, graft failure or secondary malignancy after previous 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 9/10 or 10/10 allele match after four digit typing in human leucocyte antigen (HLA)-A, B, C, DRB1 and DQB1 antigens.
4. Patients with ALL or AML in complete morphologic remission (blast counts <5% in BM) and patients with MDS or JMML with blast counts < 20% in BM at study entry.
5. Age at time of registration from 28 days to less than 18 years of age.
6. Lansky (patients aged <16 years) or Karnofsky (patients aged = 16 years) performance score of at least 70%.
7. Written informed consent of the parents/ legal guardians and patient assent/consent according to national regulations.
8. Females of child-bearing potential or male patients’ partners 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 6 months thereafter.
9. Negative pregnancy test for females of child-bearing potential.
Are the trial subjects under 18? yes
Number of subjects for this age range: 70
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

1. Third or later allo-HSCT.
2. HSCT from haploidentical or umbilical cord blood donor.
3. Symptomatic involvement of central nervous system (CNS) at study entry.
4. Treatment with cytotoxic drugs within 10 days prior to day 6.
5. Obese paediatric patients with body mass index: weight (kg)/[height (m)]² > 30 kg/m².
6. Solid tumours (e.g. neuroblastoma, peripheral neuroectodermal tumour [PNET], Ewing sarcoma).
7. Fanconi anaemia and other deoxyribonucleic acid (DNA) breakage repair disorders.
8. Impaired liver function indicated by Bilirubin > three times the upper limit of normal (ULN) or aspartate aminotransferase/alanine aminotransferase (AST/ALT) > five times ULN or active infectious hepatitis.
9. Impaired renal function indicated by estimated glomerular filtration rate ([GFR], according to the Schwartz formula) < 60 mL/min/1,73m2.
10. Impaired cardiac function: severe cardiac insufficiency indicated by left ventricle ejection fraction (LVEF) 35%.
11. Requirement for supplementary continuous oxygen.
12. Severe active infection requiring deferral of conditioning.
13. Human immunodeficiency virus (HIV) positivity.
14. Known pregnancy, breast feeding.
15. Known hypersensitivity to Treosulfan and/or Fludarabine.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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