Study of Association of Arsenic Trioxide (ATO) and Ascorbic Acid in Myelodysplastic Syndromes

Condition(s) targeted: Myelodysplastic Syndromes

Intervention: ATO + Ascorbic acid (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Associazione Italiana per lo Studio delle Sindromi Mielodisplastiche

Official(s) and/or principal investigator(s):
Alessandro Levis, MD, Study Director, Affiliation: S.O.C. di Ematologia, Azienda Ospedaliera SS Antonio e Biagio, Alessandria. Via Venezia 18 - 15100 - Alessandria

Overall contact:
Daniela Gioia, PhD, Phone: 0131/206129, Email: dgioia@ospedale.al.it

This is a prospective, multicenter phase II trial designed to evaluate the safety and activity of the combination of association of arsenic trioxide (ATO) and ascorbic acid in patients with myelodysplastic syndromes

Official title: Phase II Multicenter Study of Association of Arsenic Trioxide (ATO) and Ascorbic Acid in Myelodysplastic Syndromes

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: TO evaluate the erythroid response rate (major), according to the International Working Group (IWG) criteria (42) after four months of treatment with the association of ATO and ascorbic acid.

Secondary outcome: To evaluate platelets and granulocyte response according to the International Working Group (IWG) criteria (42) after four months of treatment with the association of ATO and ascorbic acid

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Patients affected by myelodysplastic syndromes, entering in one of the following groups:

1. Myelodysplastic syndromes independent of WHO diagnostic classification (43) and IPSS prognostic score (2), when present at least one of the following abnormalities:

- 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 chemotherapy regimens.

2. Presence of one ore more cytopenias characterised by one ore more of the following elements:

- 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 failure.

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.

Exclusion Criteria:

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.

Daniela Gioia, PhD, Phone: 0131/206129, Email: dgioia@ospedale.al.it

Ospedale SS Antonio, Biagio e Cesare Arrigo, Alessandria, Italy; Recruiting
Alessandro Levis, MD, Principal Investigator

Ospedale Cardinal Massaia, Asti, Italy; Recruiting
Giorgio Ciravegna, MD, Principal Investigator

Spedali Civili, Brescia, Italy; Recruiting
Giuseppe Rossi, MD, Principal Investigator

Ospedale Maggiore, Chieri, Italy; Recruiting
Gianni Cametti, MD, Principal Investigator

Ospedale civico di Chivasso, Chivasso (TO), Italy; Recruiting
Antonella Darbesio, MD, Principal Investigator

Ospedale Santa Croce e Carle, Cuneo, Italy; Recruiting
Andrea Gallamini, MD, Principal Investigator

AOS San Gerardo de' Tintori, Monza, Italy; Recruiting
Enrico Pogliani, MD, Principal Investigator

Università Avogadro Divisione di Ematologia, Novara, Italy; Recruiting
Gianluca Gaidano, MD, Principal Investigator

Ospedale San Luigi Gonzaga Divisione di Ematologia, Orbassano (TO), Italy; Recruiting
Giuseppe Saglio, MD, Principal Investigator

Azienda Ospedaliera Perugia, Perugia, Italy; Recruiting
Anna Maria Liberati, MD, Principal Investigator

Ospedale San Giovanbni Battista-Molinette, Torino, Italy; Recruiting
Umberto Vitolo, MD, Principal Investigator

Ospedale San Giovanni Battista -Molinette, Torino, Italy; Recruiting
Mario Boccadoro, MD, Principal Investigator

Ospedale San Bortolo, Vicenza, Italy; Recruiting
Eros Di Bona, MD, Principal Investigator

Starting date: September 2005
Last updated: December 4, 2008