None listed
Conditions
Interventions
Vidaza will be given IV for 7 days with a 28-day interval.
In this study 2 subgroups of pediatric MDS and JMML patients are eligible, and will be enrolled in 2 different strata:
1. Stratum 1: Relaps
2. Stratum 2: 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.
Sponsors
Erasmus MC, Rotterdam, The Netherlands
Eligibility
Inclusion criteria
Inclusion criteria: 1. Established diagnosis of relapsed MDS or JMML according to EWOG-criteria, after a prior stem cell transplantation; 2. 1 month to ≤ 18 years old; 3. Lansky play score > 60; or Karnofsky performance status > 60; 4. Life expectancy ≥ 3 months; 5. Normal renal function defined as less than or equal to NCI-CTCAE grade 1 (max 1.5 x ULN); 6. Normal liver function defined as less than or equal to NCI-CTCAE grade 1 (max 2.5 x ULN for transaminases and bilirubin); 7. No other chemotherapy within 3 weeks of start of study medication; For 6-MP or low-dose cytarabine in JMML patients 1 week wash-out time is sufficient. 8. For JMML patients: no oxygen need due to pulmonary infiltration and saturation >92% without need for oxygen therapy; 9. For JMML patients: peripheral blood monocyte count > 1.0x109/l 10. For relapsed patients: minimum 3 months following stem cell transplantation, and recovery of all acute toxic effects of prior chemotherapy/stem-cell transplantation; 11. Able to comply with scheduled follow-up and with management of toxicity; 12. Reproductive Function • Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment. • Female patients with infants must agree not to breastfeed their infants while on this study. • Male and female patients of child-bearing potential must agree to use an highly effective method of contraception approved by the investigator during the study and for 90 days after the last dose of azacitidine. • Highly effective methods of contraception include (but not exclusively) the following contraceptive methodsFor patients with childbearing potential, a negative pregnancy test should be available; 13. Written informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations
Exclusion criteria
Exclusion criteria: 1. Prior or current history: o Other serious illnesses or medical conditions o Genetic abnormalities indicative of AML 2. JMML patients in whom a diagnosis of Noonan syndrome is suspected based on clinical history and/or presenting symptoms 3. Patients with secondary MDS with underlying bone-marrow failure syndromes or with familial MDS 4. Isolated extramedullary disease 5. Symptomatic CNS-involvement 6. Current uncontrolled infection 7. Cardiac toxicity (shortening fraction below 28%) 8. Concurrent treatment with any other anti-cancer therapy is not allowed 9. Pregnant or lactating patients 10. Patients who cannot be regularly followed up for psychological, social, familial or geographic reasons 11. Patient with expected non-compliance to toxicity management guidelines 12. Prior treatment with a demethylating agent 13. Allergy to azacitidine or mannitol.<
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The current study aims to establish the recommended dose, safety and preliminary efficacy of azacitidine administered IV in children with advanced newly diagnosed or relapsed/refractory MDS or JMML, in 4 different subgroups (strata) of patients. Recommended dose will be determined by: 1. Dose-limiting toxicities; 2. DLTs are AEs considered at least possibly drug-related and will be limited to the first course of azacitidine. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To determine the safety and tolerability of azacitidine per stratum; 2. To determine (preliminary) the hematological remission rate in these patients; 3. To describe the durability of response and long-term follow-up, including that of patients undergoing stem-cell transplant after treatment with azacitidine; 4. To determine the plasma pharmacokinetic parameters of azacitidine; 5. To study the pharmacodynamic effects of azacitidine in pediatric MDS and JMML. Efficacy will be determined by response definitions: 1. For advanced MDS: Cheson et al, 2006; 2. For JMML :Chan et al, 2009. | — |
Contacts
Public ContactC.M. Zwaan
Dept. of Pediatric Oncology-Hematology Erasmus MC-Sophia Children's Hospital POB 2060
Outcome results
None listed