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

This study has been terminated.
(difficulties of enrollement)
Sponsor:
Collaborator:
Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte
Information provided by:
Fondazione Italiana Sindromi Mielodisplastiche Onlus
ClinicalTrials.gov Identifier:
NCT00803530
First received: December 4, 2008
Last updated: June 27, 2011
Last verified: June 2011
  Purpose

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 Intervention Phase
Myelodysplastic Syndromes
Drug: ATO + Ascorbic acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Multicenter Study of Association of Arsenic Trioxide (ATO) and Ascorbic Acid in Myelodysplastic Syndromes

Resource links provided by NLM:


Further study details as provided by Fondazione Italiana Sindromi Mielodisplastiche Onlus:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 55
Study Start Date: September 2005
Study Completion Date: August 2010
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00803530

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 Onlus
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

No publications provided

Responsible Party: Alessandro Levis, Azienda Ospedaliera SS Antonio e Biagio, Alessandria.
ClinicalTrials.gov Identifier: NCT00803530     History of Changes
Other Study ID Numbers: AISSM02A, EudracT Number 2005-001321-28
Study First Received: December 4, 2008
Last Updated: June 27, 2011
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Fondazione Italiana Sindromi Mielodisplastiche Onlus:
myelodysplastic syndromes
arsenic trioxide
ascorbic acid

Additional relevant MeSH terms:
Ascorbic Acid
Arsenic trioxide
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Growth Substances
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014