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

Study Overview
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Brief Summary
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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

Official Title
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Comparison Between Erythropoietin and Erythropoietin Associated to Differentiating Therapy With Acid 13-cis-retinoic and Dihydroxyvitamin D3 in Myelodysplastic Syndromes Without Excess of Blasts

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: infusion A: rEPO
* Drug: B Infusion rEPO combined with vitamins pills


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infusion A: rEPO<br>rEPO for 4 mounths consequently | Drug: infusion A: rEPO<br>* 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.<br>|
| Experimental: Infusion B combined r-EPO<br>rEPO in association with acid 13-cis-retinoic acid and Dihydroxyvitamin D3 for 4 mounths consequently | Drug: B Infusion rEPO combined with vitamins pills<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| To evaluate the quality of life improvement due to therapy. |  | 8 mounths | 
| To evaluate the percentage of leukemic progression. |  | 20 mounths | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndromes, Erythropoietin, Acid 13-Cis-Retinoic, Dihydroxyvitamin D3, low or intermediate-1 IPSS, MDS low risk