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

Primary Purpose

Myelodysplastic Syndromes

Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
ATO + Ascorbic acid
Sponsored by
Fondazione Italiana Sindromi Mielodisplastiche-ETS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring myelodysplastic syndromes, arsenic trioxide, ascorbic acid

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Ospedale SS Antonio, Biagio e Cesare Arrigo
  • Ospedale Cardinal Massaia
  • Spedali Civili
  • Ospedale Maggiore
  • Ospedale civico di Chivasso
  • Ospedale Santa Croce e Carle
  • AOS San Gerardo de' Tintori
  • Università Avogadro Divisione di Ematologia
  • Ospedale San Luigi Gonzaga Divisione di Ematologia
  • Azienda Ospedaliera Perugia
  • Ospedale San Giovanbni Battista-Molinette
  • Ospedale San Giovanni Battista -Molinette
  • Ospedale San Bortolo

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

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.

Outcomes

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.

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

Full Information

First Posted
December 4, 2008
Last Updated
June 27, 2011
Sponsor
Fondazione Italiana Sindromi Mielodisplastiche-ETS
Collaborators
Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte
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1. Study Identification

Unique Protocol Identification Number
NCT00803530
Brief Title
Study of Association of Arsenic Trioxide (ATO) and Ascorbic Acid in Myelodysplastic Syndromes
Official Title
Phase II Multicenter Study of Association of Arsenic Trioxide (ATO) and Ascorbic Acid in Myelodysplastic Syndromes
Study Type
Interventional

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Terminated
Why Stopped
difficulties of enrollement
Study Start Date
September 2005 (undefined)
Primary Completion Date
January 2007 (Actual)
Study Completion Date
August 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Fondazione Italiana Sindromi Mielodisplastiche-ETS
Collaborators
Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

4. Oversight

Data Monitoring Committee
No

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes
Keywords
myelodysplastic syndromes, arsenic trioxide, ascorbic acid

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ATO + Ascorbic acid
Intervention Description
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.
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients affected by myelodysplastic syndromes, entering in one of the following groups: 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. 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. 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. 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. ECOG Performance status ≤ 2. Aged from 18 to 80. Life expectancy > 4 months. Creatinine level < 1.5 mg/dl. Liver function tests, including ASL-ALT-alkaline phosphatase lower than 3xULN No previous treatment with chemotherapy, growth factors, cytokines or other experimental treatment within 4 weeks of starting treatment. No history of clinically significant cardiac disease, including congestive heart failure. Cytogenetic evaluation available. Sending of both peripheral blood and bone marrow sample to the central laboratory for EVI-1 rearrangement evaluation. Written Informed consent. Exclusion Criteria: Patients affected by myelodysplastic syndromes entering in categories other than those foreseen by inclusion criteria point 1. 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. All patients that might be candidate to allogenic stem cell transplantation. Patients that might be candidate to a first line immunosuppressive therapy. ECOG Performance status > 2. Age lower than 18 or higher then 80. Life expectancy < 4 months. Creatinine level > 1.5 mg/dl. Liver function tests, including ASL-ALT-alkaline phosphatase higher than 3xULN Treatment with chemotherapy, growth factors, cytokines or other experimental treatment within 4 weeks of starting treatment. Clinically significant cardiac disease, including congestive heart failure, rhythm abnormalities, QT time > 460m/s, or need of anti-arrhythmic drugs. Concurrent co-morbid medical condition which might exclude administration of therapy, as judged by individual investigator. Absence of cytogenetic evaluation. Participation at same time in another study in which investigational drugs are used. Absence of written Informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alessandro Levis, MD
Organizational Affiliation
S.O.C. di Ematologia, Azienda Ospedaliera SS Antonio e Biagio, Alessandria. Via Venezia 18 - 15100 - Alessandria
Official's Role
Study Director
Facility Information:
Facility Name
Ospedale SS Antonio, Biagio e Cesare Arrigo
City
Alessandria
Country
Italy
Facility Name
Ospedale Cardinal Massaia
City
Asti
Country
Italy
Facility Name
Spedali Civili
City
Brescia
Country
Italy
Facility Name
Ospedale Maggiore
City
Chieri
Country
Italy
Facility Name
Ospedale civico di Chivasso
City
Chivasso (TO)
Country
Italy
Facility Name
Ospedale Santa Croce e Carle
City
Cuneo
Country
Italy
Facility Name
AOS San Gerardo de' Tintori
City
Monza
Country
Italy
Facility Name
Università Avogadro Divisione di Ematologia
City
Novara
Country
Italy
Facility Name
Ospedale San Luigi Gonzaga Divisione di Ematologia
City
Orbassano (TO)
Country
Italy
Facility Name
Azienda Ospedaliera Perugia
City
Perugia
Country
Italy
Facility Name
Ospedale San Giovanbni Battista-Molinette
City
Torino
Country
Italy
Facility Name
Ospedale San Giovanni Battista -Molinette
City
Torino
Country
Italy
Facility Name
Ospedale San Bortolo
City
Vicenza
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
22964015
Citation
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.
Results Reference
derived

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

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