Multicentric Study Comparison Between Erythropoietin and Erythropoietin Associated to Differentiating Therapy With Acid 13-Cis-Retinoic and Dihydroxyvitamin D3 in Myelodysplastic Syndromes Without Excess of Blasts - Full Text View

Sponsors and Collaborators:	Associazione Italiana per lo Studio delle Sindromi Mielodisplastiche Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica (CPO) Piemonte
Information provided by:	Associazione Italiana per lo Studio delle Sindromi Mielodisplastiche
ClinicalTrials.gov Identifier:	NCT00804050

Purpose

This is a prospective, randomized multicenter phase III clinical trial designed to evaluate the safety and activity of comparison between Erythropoietin and Erythropoietin Associated to Differentiating Therapy With Acid 13-Cis-Retinoic and Dihydroxyvitamin D3 in Myelodysplastic Syndromes Without Excess of Blasts

Condition	Intervention	Phase
Myelodysplastic Syndromes	Drug: infusion A: rEPO Drug: B Infusion rEPO combined with vitamins pills	Phase III

Drug Information available for: Epoetin alfa Erythropoietin Isotretinoin Tretinoin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title:	Comparison Between Erythropoietin and Erythropoietin Associated to Differentiating Therapy With Acid 13-Cis-Retinoic and Dihydroxyvitamin D3 in Myelodysplastic Syndromes Without Excess of Blasts

Further study details as provided by Associazione Italiana per lo Studio delle Sindromi Mielodisplastiche:

Primary Outcome Measures:

study of comparison between standard theraphy rEPO (40.000unit/week) and association therapy between rEPO (40.000unit/week)plus Acid 13-Cis-Retinoic and Dihydroxyvitamin D3 [ Time Frame: After 8 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

TO evaluate if,the patients without eritroyd response at the end of the 4° month of therapy, the increase of dose of rEPO to 80.000 U / week allows to get an increase of valued response at the end of the 8° month. [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
To evaluate if there is a difference of duration in the eritroyd response with standard therapy rEPO in comparison with association therapy rEPO plus Acid 13-Cis-Retinoic and Dihydroxyvitamin D3. [ Time Frame: 20 mounths ] [ Designated as safety issue: Yes ]
To evaluate the existing relationships among eritroyd response and clinical-biological parameters at baseline of anemia, subclass of MDS, silky dosing of the EPO etc. [ Time Frame: 20 mounths ] [ Designated as safety issue: Yes ]
To evaluate the quality of life improvement due to therapy. [ Time Frame: 8 mounths ] [ Designated as safety issue: No ]
To evaluate the percentage of leukemic progression. [ Time Frame: 20 mounths ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	184
Study Start Date:	March 2007
Estimated Study Completion Date:	March 2010
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Infusion A: rEPO: Experimental rEPO for 4 mounths consequently	Drug: infusion A: rEPO rEPO 40.000 unit/week for 4 mounths, then patients who have obtained an erythroid response, will continue for another 4 months with therapy rEPO. Patients who have not obtained an erythroid response, will increase the dose rEPO to 80,000 units per week for an additional 4 months.
Infusion B combined r-EPO: Experimental rEPO in association with acid 13-cis-retinoic acid and Dihydroxyvitamin D3 for 4 mounths consequently	Drug: B Infusion rEPO combined with vitamins pills rEPO 40.000 unit/week plus acid 13 cis-retinoic (20 mg/die) plus Dihydroxyvitamin D3 (1 μg os/die), for 4 mounths. Patients who have obtained an erythroid response will continue for another 4 months with the same therapy. Patients who have not obtained an erythroid will increase the dose of rEPO to 80,000 units per week for additional 4 months.Patients also will continue with the same doses of acid 13-cis-retinoic acid and Dihydroxyvitamin D3

Arms

Assigned Interventions

Infusion A: rEPO: Experimental

rEPO for 4 mounths consequently

Drug: infusion A: rEPO

rEPO 40.000 unit/week for 4 mounths, then patients who have obtained an erythroid response, will continue for another 4 months with therapy rEPO. Patients who have not obtained an erythroid response, will increase the dose rEPO to 80,000 units per week for an additional 4 months.

Infusion B combined r-EPO: Experimental

rEPO in association with acid 13-cis-retinoic acid and Dihydroxyvitamin D3 for 4 mounths consequently

Drug: B Infusion rEPO combined with vitamins pills

rEPO 40.000 unit/week plus acid 13 cis-retinoic (20 mg/die) plus Dihydroxyvitamin D3 (1 μg os/die), for 4 mounths. Patients who have obtained an erythroid response will continue for another 4 months with the same therapy. Patients who have not obtained an erythroid will increase the dose of rEPO to 80,000 units per week for additional 4 months.Patients also will continue with the same doses of acid 13-cis-retinoic acid and Dihydroxyvitamin D3

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age higher than 18;
Confirmed diagnosis by osseous biopsy and bone marrow cyto-morphologic counts of blast cells, of Myelodysplastic syndrome without excess of blasts: "refractary anemia", "refractary anemia with rings sideroblasts", "refractary citopenya with multilineage dysplasia", " refractary citopenya with multilineage dysplasia and rings sideroblasts" or "5q-syndrome" without excess of blasts based on WHO classification (appendix).
Low or intermediate-1 IPSS (appendix).
Hb < 11g/dl.
rEPO serum level < 500mU/L.
Women in menopause from at least one year.
Informed consent

Exclusion Criteria:

Myelodisplastic syndrome with excess of blasts (RAEB).
IPSS score intermediate-2 or high (appendix).
Forecasted allogeneic bone marrow transplant within 1 year after diagnosis(patients younger than 60 years, transfusion dependents or with serious leuko/thrombocytopenia and HLA compatible family donor).Considering the time needed to perform this procedure, the indication of a transplant from non-consanguineous donor has no contraindication to the inclusion in this protocol of the response to rEPO therapy ± differentiating therapy.
Renal failure with creatininemia value greater than 3 times the normal limit.
Chronic hepatophaty with bilirubinemia value greater than 3 times the normal limit and/or AST or ALT or ALP values greater than 5 times the normal limit.
Presence of second tumor or other serious pathology with life expectancy lower than one year.
Presence of neurologic or psychiatric pathologies that make the patient unreliable in the acquisition of drugs.
Allergy/intolerance known to use drugs.
Pregnant women.
Women of childbearing age or in menopause from less than one year.
Age < 18 years old.
HIV positive.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00804050

Contacts

Contact: Daniela Gioia, PhD

0131/206129

dgioia@ospedale.al.it

Locations

Italy
Ospedale SS. Antonio, Biagio e Cesare Arrigo	Recruiting
Alessandria, Italy
Principal Investigator: Alessandro Levis, MD
Ospedale San Giovanni Battista Molinette	Not yet recruiting
Torino, Italy
Principal Investigator: Mario Boccadoro, MD
Ospedale Santa Croce	Not yet recruiting
Fano (PU), Italy
Principal Investigator: Marino Brunori, MD
Ospedale Maggiore	Not yet recruiting
Chieri (TO), Italy
Principal Investigator: Gianni Cametti, MD
Ospedale Santo Spirito	Not yet recruiting
Casale (AL), Italy
Principal Investigator: Massimo Capra Marzani, MD
Ospedale San Bortolo	Not yet recruiting
Vicenza, Italy
Principal Investigator: Eros Di Bona, MD
Ospedale Maggiore della Carità	Not yet recruiting
Novara, Italy
Principal Investigator: Gianluca Gaidano, MD
Ospedale Santa Croce e Carle	Recruiting
Cuneo, Italy
Principal Investigator: Andrea Gallamini, MD
Ospedale San Giovanni Battista Molinette	Not yet recruiting
Torino, Italy
Principal Investigator: Eugenio Gallo, MD
Ospedale degli Infermi	Recruiting
Biella, Italy
Principal Investigator: Giovanni Bertinieri, MD
Ospedale San Martino	Not yet recruiting
Genova, Italy
Principal Investigator: Marco Gobbi, MD
Policlinico dell'Annunziata	Not yet recruiting
Cosenza, Italy
Principal Investigator: Fortunato Morabito, MD
Ospedale Cardinale Panico	Not yet recruiting
Tricase (LE), Italy
Principal Investigator: Vincenzo Pavone, MD
Ospedale San Gerardo	Not yet recruiting
Monza (MI), Italy
Principal Investigator: Enrico Pogliani, MD
Spedali civili	Recruiting
Brescia, Italy
Principal Investigator: Giuseppe Rossi, MD
Ospedale Sant'Andrea	Not yet recruiting
Vercelli, Italy
Principal Investigator: Alberto Santagostino, MD
Istituto clinico Humanitas	Not yet recruiting
Rozzano (MI), Italy
Principal Investigator: Armando Santoro, MD
Ospedale Civile	Not yet recruiting
Ovada (AL), Italy
Principal Investigator: Paola Varese, MD
Ospedale civile	Not yet recruiting
Ivrea (TO), Italy
Principal Investigator: Mauro Girotto, MD

Sponsors and Collaborators

Associazione Italiana per lo Studio delle Sindromi Mielodisplastiche

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

Investigators

Study Director:	Dario Ferrero, MD	University of Torino - Ospedale San Giovanni Battista
Study Director:	Alessandro Levis, MD	Ospedale SS. Antonio, Biagio e Cesare Arrigo

More Information

Responsible Party:	University of Torino - Ospedale S Giovanni Battista ( Dario Ferrero, MD )
Study ID Numbers:	EPO2006-AISSM04, 2006-006482-16
Study First Received:	December 5, 2008
Last Updated:	December 5, 2008
ClinicalTrials.gov Identifier:	NCT00804050
Health Authority:	Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Associazione Italiana per lo Studio delle Sindromi Mielodisplastiche:

Myelodysplastic Syndromes
Erythropoietin
Acid 13-Cis-Retinoic

Dihydroxyvitamin D3
low or intermediate-1 IPSS
MDS low risk

Study placed in the following topic categories:

Epoetin Alfa
Myelodysplastic syndromes
Preleukemia
Precancerous Conditions
Hematologic Diseases
Myelodysplasia

Myelodysplastic Syndromes
Isotretinoin
Tretinoin
Bone Marrow Diseases
Dihydroxycholecalciferols

Additional relevant MeSH terms:

Disease
Hematinics
Growth Substances
Physiological Effects of Drugs
Hematologic Agents
Bone Density Conservation Agents
Pharmacologic Actions

Neoplasms
Pathologic Processes
Syndrome
Vitamins
Therapeutic Uses
Micronutrients

ClinicalTrials.gov processed this record on January 16, 2009