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

Myelodysplastic Syndromes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00803530
• Other study ID #: AISSM02A
• Secondary ID: EudracT Number 2
• Status: Terminated
• Phase: Phase 2
• First received: December 4, 2008
• Last updated: June 27, 2011
• Start date: September 2005
• Est. completion date: August 2010

Study information

• Verified date: June 2011
• Source: Fondazione Italiana Sindromi Mielodisplastiche Onlus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 55
• Est. completion date: August 2010
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• ATO + Ascorbic acid
ATO will be diluted in 250 ml of normal saline solution at a dosage of 0.3 mg/Kg during the first week of therapy and at a dosage of 0.25 mg/Kg during the subsequent weeks (week 2 to 16), and administered intravenously over a 1-2 hour period. The dose of ascorbic acid will be 1000 mg in 100 cc D5W or normal saline solution (NaCl 0.9 %) (protected from light and air) administered as an IV infusion over 15 to 30 minutes. The dosing solution is not to be mixed with any alkaline solution.

Locations

Country	Name	City	State
Italy	Ospedale SS Antonio, Biagio e Cesare Arrigo	Alessandria
Italy	Ospedale Cardinal Massaia	Asti
Italy	Spedali Civili	Brescia
Italy	Ospedale Maggiore	Chieri
Italy	Ospedale civico di Chivasso	Chivasso (TO)
Italy	Ospedale Santa Croce e Carle	Cuneo
Italy	AOS San Gerardo de' Tintori	Monza
Italy	Università Avogadro Divisione di Ematologia	Novara
Italy	Ospedale San Luigi Gonzaga Divisione di Ematologia	Orbassano (TO)
Italy	Azienda Ospedaliera Perugia	Perugia
Italy	Ospedale San Giovanbni Battista-Molinette	Torino
Italy	Ospedale San Giovanni Battista -Molinette	Torino
Italy	Ospedale San Bortolo	Vicenza

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione Italiana Sindromi Mielodisplastiche Onlus	Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		16 mounths	Yes
Secondary	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		16 mounths	Yes