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: 21.1 Level: LLT Classification code 10054439 Term: Juvenile chronic myelomonoc
Conditions
Sponsors
medac GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Third or later allo-HSCT. 2. HSCT from haploidentical or umbilical cord blood donor. 3. Concomitant involvement of central nervous system (e.g. presence of the leukaemic blasts in the cerebrospinal fluid (CSF) 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. Concomitant solid tumours (e.g. neuroblastoma, peripheral neuroectodermal tumour [PNET], Ewing sarcoma). 7. Fanconi anaemia and other deoxyribonucleic acid (DNA) breakage repair disorders; secondary leukaemia developed from the Fanconi anaemia or other 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) > ten times ULN, or clinical significant coagulopathy, or active infectious hepatitis with clinical evidence. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Freedom from transplant (treatment)-related mortality, defined as death from any transplant-related cause from the day of first administration of study medication until day +100 after HSCT. ; Secondary Objective: Evaluation of: 1. leukocyte, neutrohil and platelet engraftment after HSCT 2. safety including early toxicity, until day +100 after HSCT, SARs until the end of the longer-term follow-up phase 3. HSOS, lung toxicity, hepatic toxicity and infections of any CTCAE grade until day +100 4. donor-type chimerism on day +28, day +100 and 12 months after HSCT 5. NRM, TRM, graft failure rate, incidence of relapse/progression, RFS/PFS and OS until 12 months after HSCT 6. incidence and severity of acute (until day +100) and chronic (until 12 months after HSCT) graft versus host disease (aGvHD/cGvHD) 7. use of rescue therapies including DLIs and further conditioning regimens 8. PK parameters of Treosulfan and its epoxides and to develop a PK model for assessing relevant covariates 9. NRM, TRM, secondary graft failures, relapse/progression, RFS/PFS, OS and cGvHD during the longer-term follow-up phase ;Primary end point(s): Freedom from transplant (treatment)-related mortality (TRM), defined as death from any transplant-related cause from the day of first administration of study medication until day +100 after HSCT ;Timepoint(s) of evaluation of this end point: Day + 100 after HSCT | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Day 28, 12 months after HSCT and/or until the end of the longer-term follow-up phase ; Secondary end point(s): Evaluation of: 1. donor type engraftment after HSCT, defined as first of three consecutive days for each of the following four criteria: - a leukocyte count of more than 1 x 109/L - an absolute neutrophil count (ANC) of more than 0.5 x 109/L - a platelet count of at least 20 x 109/L - a platelet count of at least 50 x 109/L 2. safety including early toxicity, based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 until day +100 after HSCT, serious adverse reactions (SARs) until the end of longer-term follow-up phase 3. hepatic sinusoidal obstruction syndrome (HSOS), lung toxicity (CTCAE term pulmonary fibrosis), hepatic toxicity and infections of any CTCAE grade (non-serious and serious) until day +100 4. donor-type chimerism on day +28, day +100 and 12 months after HSCT 5. non relapse mortality (NRM), TRM, incidence of relapse/progression, relapse-free/progression-free survival (RFS/PFS) and overall survival (OS) until 12 months after HSCT 6. incidence and severity of acute (until day +100) and chronic (until 12 months after HSCT) graft versus host disease (aGvHD/cGvHD) 7. use of rescue therapies including donor-lymphocyte infusions (DLIs) and further conditioning regimens 8. PK parameters of Treosulfan and its epoxides and to develop a PK model for assessing relevant covariates 9. secondary graft failure, cGvHD, OS, TRM and NRM during the longer-term follow-up phase | — |
Countries
Austria, Czech Republic, Germany, Italy, Poland, United Kingdom
Contacts
Public ContactGhalia Hachem
Syneos Health UK Limited
Outcome results
None listed