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

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00804050
• Other study ID #: EPO2006-AISSM04
• Secondary ID: 2006-006482-16
• Status: Terminated
• Phase: Phase 3
• First received: December 5, 2008
• Last updated: June 27, 2011
• Start date: March 2007
• Est. completion date: March 2010

Study information

• Verified date: June 2011
• Source: Fondazione Italiana Sindromi Mielodisplastiche Onlus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 184
• Est. completion date: March 2010
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age higher than 18;

2. 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).

3. Low or intermediate-1 IPSS (appendix).

4. Hb < 11g/dl.

5. rEPO serum level < 500mU/L.

6. Women in menopause from at least one year.

7. Informed consent

Exclusion Criteria:

1. Myelodisplastic syndrome with excess of blasts (RAEB).

2. IPSS score intermediate-2 or high (appendix).

3. 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.

4. Renal failure with creatininemia value greater than 3 times the normal limit.

5. 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.

6. Presence of second tumor or other serious pathology with life expectancy lower than one year.

7. Presence of neurologic or psychiatric pathologies that make the patient unreliable in the acquisition of drugs.

8. Allergy/intolerance known to use drugs.

9. Pregnant women.

10. Women of childbearing age or in menopause from less than one year.

11. Age < 18 years old.

12. HIV positive.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

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.
• 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

Locations

Country	Name	City	State
Italy	Ospedale SS. Antonio, Biagio e Cesare Arrigo	Alessandria
Italy	Ospedale degli Infermi	Biella
Italy	Spedali civili	Brescia
Italy	Ospedale Santo Spirito	Casale (AL)
Italy	Ospedale Maggiore	Chieri (TO)
Italy	Policlinico dell'Annunziata	Cosenza
Italy	Ospedale Santa Croce e Carle	Cuneo
Italy	Ospedale Santa Croce	Fano (PU)
Italy	Ospedale San Martino	Genova
Italy	Ospedale civile	Ivrea (TO)
Italy	Ospedale San Gerardo	Monza (MI)
Italy	Ospedale Maggiore della Carità	Novara
Italy	Ospedale Civile	Ovada (AL)
Italy	Istituto clinico Humanitas	Rozzano (MI)
Italy	Ospedale San Giovanni Battista Molinette	Torino
Italy	Ospedale Cardinale Panico	Tricase (LE)
Italy	Ospedale Sant'Andrea	Vercelli
Italy	Ospedale San Bortolo	Vicenza

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione Italiana Sindromi Mielodisplastiche Onlus	Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		After 8 months	Yes
Secondary	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.		8 months	Yes
Secondary	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.		20 mounths	Yes
Secondary	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.		20 mounths	Yes
Secondary	To evaluate the quality of life improvement due to therapy.		8 mounths	No
Secondary	To evaluate the percentage of leukemic progression.		20 mounths	Yes