Phase II Multicenter Study of Association of Arsenic Trioxide (ATO) and Ascorbic Acid in Myelodysplastic Syndromes
1. Patients affected by myelodysplastic syndromes, entering in one of the following
1. Myelodysplastic syndromes independent of WHO diagnostic classification (43) and
IPSS prognostic score (2), when present at least one of the following
- 3q26 chromosome rearrangement.
- High EVI-1 transcript levels.
2. Myelodysplastic syndromes without excess of blasts (non-RAEB patients) at low or
intermediate-1 score risk according to the IPSS (2), as a second line treatment
option, after a failure to the first line treatment with erythropoietin +/-
G-CSF, immunosuppressive therapy, or other initial treatment modality.
3. Non RAEB patients at intermediate-2 or high risk score or RAEB patients at any
prognostic score, who are non candidate to treatment with conventional
2. Presence of one ore more cytopenias characterised by one ore more of the following
- Transfusions dependence.
- Hb< 11 gr/dl
- Platelet count < 50x109/L
- Absolute neutrophil count < .5x109/L.
3. ECOG Performance status ≤ 2.
4. Aged from 18 to 80.
5. Life expectancy > 4 months.
6. Creatinine level < 1.5 mg/dl.
7. Liver function tests, including ASL-ALT-alkaline phosphatase lower than 3xULN
8. No previous treatment with chemotherapy, growth factors, cytokines or other
experimental treatment within 4 weeks of starting treatment.
9. No history of clinically significant cardiac disease, including congestive heart
10. Cytogenetic evaluation available.
11. Sending of both peripheral blood and bone marrow sample to the central laboratory for
EVI-1 rearrangement evaluation.
12. Written Informed consent.
1. Patients affected by myelodysplastic syndromes entering in categories other than
those foreseen by inclusion criteria point 1.
2. Absence of cytopenia defined as the contemporarily presence of all the following
conditions: a) no transfusion need; b) Hb > 11 gr/dl; c) platelet count > 50x109/L;
d) absolute neutrophil count > .5x109/L.
3. All patients that might be candidate to allogenic stem cell transplantation.
4. Patients that might be candidate to a first line immunosuppressive therapy.
5. ECOG Performance status > 2.
6. Age lower than 18 or higher then 80.
7. Life expectancy < 4 months.
8. Creatinine level > 1.5 mg/dl.
9. Liver function tests, including ASL-ALT-alkaline phosphatase higher than 3xULN
10. Treatment with chemotherapy, growth factors, cytokines or other experimental
treatment within 4 weeks of starting treatment.
11. Clinically significant cardiac disease, including congestive heart failure, rhythm
abnormalities, QT time > 460m/s, or need of anti-arrhythmic drugs.
12. Concurrent co-morbid medical condition which might exclude administration of therapy,
as judged by individual investigator.
13. Absence of cytogenetic evaluation.
14. Participation at same time in another study in which investigational drugs are used.
15. Absence of written Informed consent.