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

NCT00803530 | Terminated Phase 2

• 2 other identifiers: AISSM02AEudracT Number 2005-001321-28
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 13

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

Conditions

Myelodysplastic Syndromes

Keywords

myelodysplastic syndromes; arsenic trioxide; ascorbic acid

Outcome Measures

Primary Outcomes (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.

  16 mounths

Secondary Outcomes (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

  16 mounths

Study Arms (1)

1

EXPERIMENTAL

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

Interventions

ATO + Ascorbic acid DRUG

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.

1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• q26 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Italiana Sindromi Mielodisplastiche-ETS: lead
• Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte: collaborator

Study Sites (13)

Ospedale SS Antonio, Biagio e Cesare Arrigo

Alessandria, Italy

Location

Ospedale Cardinal Massaia

Asti, Italy

Location

Spedali Civili

Brescia, Italy

Location

Ospedale Maggiore

Chieri, Italy

Location

Ospedale civico di Chivasso

Chivasso (TO), Italy

Location

Ospedale Santa Croce e Carle

Cuneo, Italy

Location

AOS San Gerardo de' Tintori

Monza, Italy

Location

Università Avogadro Divisione di Ematologia

Novara, Italy

Location

Ospedale San Luigi Gonzaga Divisione di Ematologia

Orbassano (TO), Italy

Location

Azienda Ospedaliera Perugia

Perugia, Italy

Location

Ospedale San Giovanbni Battista-Molinette

Torino, Italy

Location

Ospedale San Giovanni Battista -Molinette

Torino, Italy

Location

Ospedale San Bortolo

Vicenza, Italy

Location

Related Publications (1)

• 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.

  PMID: 22964015 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Alessandro Levis, MD

  S.O.C. di Ematologia, Azienda Ospedaliera SS Antonio e Biagio, Alessandria. Via Venezia 18 - 15100 - Alessandria

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 4, 2008
• First Posted: December 5, 2008
• Study Start: September 1, 2005
• Primary Completion: January 1, 2007
• Study Completion: August 1, 2010
• Last Updated: June 28, 2011

Record last verified: 2011-06

Locations

IT (13)