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

• ClinicalTrials.gov Identifier: NCT00803530
• Recruitment Status: Terminated
• First Posted: December 5, 2008
• Last Update Posted: June 28, 2011
• Sponsor: Fondazione Italiana Sindromi Mielodisplastiche-ETS
• Collaborator: Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte
• Information provided by: Fondazione Italiana Sindromi Mielodisplastiche-ETS

Study Description

Brief 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

Condition or disease	Intervention/treatment	Phase
Myelodysplastic Syndromes	Drug: ATO + Ascorbic acid	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 55 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Multicenter Study of Association of Arsenic Trioxide (ATO) and Ascorbic Acid in Myelodysplastic Syndromes
• Study Start Date: September 2005
• Actual Primary Completion Date: January 2007
• Actual Study Completion Date: August 2010

Arms and Interventions

Arm

Intervention/treatment

Experimental: 1; Loading phase (week 1): ATO 0.3 mg/Kg/die for 5 consecutive days.; Subsequent phase (from week 2 to week 16): ATO 0.25 mg/kg twice a week (day 2 and 5 of every week).; Ascorbic acid 1000 mg IV within 30 minutes after each arsenic trioxide infusion for 16 consecutive weeks.

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.

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 16 mounths ]

Secondary Outcome Measures :

1. 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 [ Time Frame: 16 mounths ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

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, Italy

Sponsors and Collaborators

Fondazione Italiana Sindromi Mielodisplastiche-ETS

Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

Investigators

• Study Director: Alessandro Levis, MD; S.O.C. di Ematologia, Azienda Ospedaliera SS Antonio e Biagio, Alessandria. Via Venezia 18 - 15100 - Alessandria

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Galimberti S, Guerrini F, Salvi F, Petrini I, Gioia D, Messa E, Palumbo GA, Cilloni D, Petrini M, Levis A. Arsenic trioxide and ascorbic acid interfere with the BCL2 family genes in patients with myelodysplastic syndromes: an ex-vivo study. J Hematol Oncol. 2012 Sep 10;5:53. doi: 10.1186/1756-8722-5-53.

• Responsible Party: Alessandro Levis, Azienda Ospedaliera SS Antonio e Biagio, Alessandria.
• ClinicalTrials.gov Identifier: NCT00803530
• Other Study ID Numbers: AISSM02A; EudracT Number 2005-001321-28
• First Posted: December 5, 2008
• Last Update Posted: June 28, 2011
• Last Verified: June 2011

Keywords provided by Fondazione Italiana Sindromi Mielodisplastiche-ETS:

myelodysplastic syndromes; arsenic trioxide; ascorbic acid

Additional relevant MeSH terms:

Preleukemia; Myelodysplastic Syndromes; Syndrome; Disease; Pathologic Processes; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Neoplasms; Ascorbic Acid; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Vitamins; Micronutrients; Nutrients; Growth Substances