Clinical trial NCT00803530: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: myelodysplastic syndromes
arsenic trioxide
ascorbic acid
Lead sponsor: Fondazione Italiana Sindromi Mielodisplastiche-ETS
Sponsor class: OTHER
Collaborators: name: Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte
First posted: 2008-12-05
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: 16 mounths
Secondary outcomes:
measure: 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
timeFrame: 16 mounths
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: Ospedale SS Antonio, Biagio e Cesare Arrigo
city: Asti
country: Italy
facility: Ospedale Cardinal Massaia
city: Brescia
country: Italy
facility: Spedali Civili
city: Chieri
country: Italy
facility: Ospedale Maggiore
city: Chivasso (TO)
country: Italy
facility: Ospedale civico di Chivasso
city: Cuneo
country: Italy
facility: Ospedale Santa Croce e Carle
city: Monza
country: Italy
facility: AOS San Gerardo de' Tintori
city: Novara
country: Italy
facility: Università Avogadro Divisione di Ematologia
city: Orbassano (TO)
country: Italy
facility: Ospedale San Luigi Gonzaga Divisione di Ematologia
city: Perugia
country: Italy
facility: Azienda Ospedaliera Perugia
city: Torino
country: Italy
facility: Ospedale San Giovanbni Battista-Molinette
city: Torino
country: Italy
facility: Ospedale San Giovanni Battista -Molinette
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
Study officials:
affiliation: S.O.C. di Ematologia, Azienda Ospedaliera SS Antonio e Biagio, Alessandria. Via Venezia 18 - 15100 - Alessandria
name: Alessandro Levis, MD
role: STUDY_DIRECTOR
References:
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.