Azacitidine in children with MDS or JMM

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 24

Inclusion Criteria

•Diagnosis of relapsed advanced primary MDS or JMML, established at initial diagnosis by the diagnostic criteria as specified in the EWOG-MDS 2006 protocol (see appendix 1), and defined as:
oRelapsed MDS:
After a documented CR or PR, this designation is defined as
- a reappearance of blasts in the peripheral blood,
- or =5% blasts in the bone marrow not attributable to any other cause (e.g. bone marrow regeneration after consolidation therapy), and confirmed with flowcytometry.
oRelapsed JMML:
After a documented CR or PR, this designation is defined as
- reappearance of organomegaly
- in combination with elevated WBC with peripheral blood monocytosis (greater than 1x109/l),
- and/or the reappearance of a cytogenetic or molecular lesion indicative of prior disease.
- In addition, clinical criteria may be used, which include objective parameters such as increase in spleen size of >50% from baseline, and/or the appearance of new skin lesions, and/or oxygen need,
- and/or blast crises/transformation to AML.
•1 month to = 18 years old
•Lansky play score = 60; or Karnofsky performance status = 60 (appendix 2)
•Life expectancy ? 3 months
•Normal renal function defined as less than or equal to NCI-CTCAE grade 1 (max 1.5 x ULN).
•Normal liver function defined as less than or equal to NCI-CTCAE grade 1 (max 2.5 x ULN for transaminases and bilirubin)
•No 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.
•For JMML patients: saturation >92% without additional supply of oxygen
•For JMML patients: peripheral blood monocyte count greater than 1.0x109/l
•For relapsed patients following HSCT: recovery of all acute toxic effects of prior chemotherapy/stem-cell transplantation.
•Able to comply with scheduled follow-up and with management of toxicity.
•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 methods:
•combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
•progestogen-only hormonal contraception associated with inhibition of ovulation
•intrauterine device (IUD)
•intrauterine hormone-releasing system ( IUS)
•sexual abstinence.
•Written informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations.
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
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

•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 azacitidine or mannitol.

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

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