D46 C93.3
Conditions
Interventions
Group 1: • stratum 1: newly diagnosed patients with primary advanced MDS (RAEB or RAEB-t) in a ‘pre stem cell transplantation window’.
Group 2: • stratum 2: relapsed patients with advanced primary MDS
Sponsors
Erasmus MC-Sophia
Eligibility
Sex/Gender
All
Age
1 Months to 18 Years
Inclusion criteria
Inclusion criteria: • stratum 1: newly diagnosed patients with primary advanced MDS (RAEB or RAEB-t) in a ‘pre stem cell transplantation window’. • stratum 2: relapsed patients with advanced primary MDS in a ‘re-transplantation window’. At relapse azacitidine may also be continued when a 2nd transplant is not feasible, as long as the patient benefits from treatment. • stratum 3: newly diagnosed patients with JMML in a ‘pre-stem cell transplantation window’. • stratum 4: relapsed patients with JMML in a ‘re-transplantation window’. Azacitidine may also be continued when a 2nd transplant is not feasible and as long as the patient benefits from treatment • stratum 5: newly diagnosed or relapsed patients with secondary advanced MDS, occurring after chemotherapy, radiotherapy and or stem-cell transplantation, or secondary cases after prior treatment for aplastic anemia.
Exclusion criteria
Exclusion criteria: • Other serious illnesses or medical conditions • Genetic abnormalities indicative of AML • JMML patients in whom a diagnosis of Noonan syndrome is suspected based on clinical history and/or presenting symptoms • Patients with secondary MDS with underlying bone-marrow failure syndromes or with familial MDS • Isolated extramedullary disease • Symptomatic CNS-involvement • Current uncontrolled infection • Cardiac toxicity (shortening fraction below 28%) • Concurrent treatment with any other anti-cancer therapy is not allowed • Pregnant or lactating patients • Patients who cannot be regularly followed up for psychological, social, familial or geographic reasons • Patient with expected non compliance to toxicity management guidelines • Prior treatment with a demethylating agent • Allergy to azicitidine or mannitol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To establish the recommended dose and preliminary efficacy of azacitidine in children with newly diagnosed and relapsed advanced MDS (either primary or secondary MDS) or JMML. | — |
Secondary
| Measure | Time frame |
|---|---|
| - To determine the safety and tolerability of azacitidine in newly diagnosed and relapsed advanced MDS (either primary or secondary MDS) and JMML - To determine (preliminary) the hematological remission rate in these patients - To describe the durability of response and long-term follow-up, including that of patients undergoing stem-cell transplant after treatment with azacitidine - To determine the plasma pharmacokinetic parameters of azacitidine - To study the pharmacodynamic effects of azacitidine in pediatric advanced MDS or JMML Initially, the aim is to recruit a total of 6 relapsed MDS or JMML patients (stratum 2, 4 or 5) at the starting dose-level. When 6 patients are treated in either of these strata, cohort 1and 3 (including newly diagnosed patients) may start enrolling patients provided the drug is safe in the relapsed setting. An independent Data Safety Monitoring Board (DSMB) will be set up to determine this. Based on the available data (safety, response, PK) following treatment of 6 patients in each of the strata, we will enrol another 6 patients per stratum at the proposed recommended dose, to expand the safety data. Therefore, we will recruit a maximum of 12 patients in each stratum, and hence 60 patients in total. Including screen failures or drop-outs we may need to recruit approximately 65 patients. The study will last approximately 4 years from first patient first visit (FPFV) to last patient last visit (LPLV). | — |
Countries
Austria, Czechia, Denmark, France, Germany, Italy, Netherlands, United Kingdom
Contacts
Public ContactCharlotte Niemeyer
Universitätsklinikum Freiburg Kinder- und Jugendklinik
Outcome results
None listed