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

This study has been terminated.
(Difficulties of enrollment)
Sponsor:
Collaborator:
Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte
Information provided by:
Fondazione Italiana Sindromi Mielodisplastiche Onlus
ClinicalTrials.gov Identifier:
NCT00804050
First received: December 5, 2008
Last updated: June 27, 2011
Last verified: June 2011
  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 3

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

Resource links provided by NLM:


Further study details as provided by Fondazione Italiana Sindromi Mielodisplastiche Onlus:

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
Study Completion Date: March 2010
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Infusion A: rEPO
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.
Experimental: Infusion B combined r-EPO
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:

  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
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, Italy
Sponsors and Collaborators
Fondazione Italiana Sindromi Mielodisplastiche Onlus
Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica 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

No publications provided

Responsible Party: Dario Ferrero, MD, University of Torino - Ospedale S Giovanni Battista
ClinicalTrials.gov Identifier: NCT00804050     History of Changes
Other Study ID Numbers: EPO2006-AISSM04, 2006-006482-16
Study First Received: December 5, 2008
Last Updated: June 27, 2011
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Fondazione Italiana Sindromi Mielodisplastiche Onlus:
Myelodysplastic Syndromes
Erythropoietin
Acid 13-Cis-Retinoic
Dihydroxyvitamin D3
low or intermediate-1 IPSS
MDS low risk

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Pathologic Processes
Precancerous Conditions
Dihydroxycholecalciferols
Epoetin alfa
Bone Density Conservation Agents
Growth Substances
Hematinics
Hematologic Agents
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vitamins

ClinicalTrials.gov processed this record on October 23, 2014