Azacitidine Combined to Epoetin Beta in International Prognostic Scoring System (IPSS) Low-risk and Intermediate-1 Myelodysplastic Syndrome (MDS) Patients, Resistant to Erythropoetin-stimulating Agents (ESA)

• Status: Completed
• Trial end date: 2014-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The study is aimed to treat low-risk MDS patients,who are dependent on red-blood cell transfusion due to disease-related anemia, and who have a proven resistance towards treatment with erythropoetin-stimulating agents (ESA). The study randomizes patients to receive a treatment with the demethylating agent 5-azacytidine alone or in combination with an ESA. The study thus evaluates, if efficacy of 5-azacytidine, notably on the red-blood cell transfusion-dependence is comparable/inferior to a combination treatment with azacitidine and an ESA (that is if 5-azacytidine can overcome the resistance towards ESA). Being a phase II study, the study assesses, duration of erythroid response, overall survival and time to progression as well as toxicity.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Groupe Francophone des Myelodysplasies
• Collaborators: Celgene Corporation; Roche Pharma AG
• Treatments: Azacitidine; Epoetin Alfa

Criteria

Inclusion Criteria:

MDS defined as

• RCMD, RA with or without ring sideroblasts

• RAEB 1, or CMML 1, if WBC < 13 G /l according to the WHO classification

• with a low or int-1 IPSS score AND

• primary or secondary resistance to epoetin alpha/ beta (> 60000 U/w) or darbepoetin (> 250ug/w), administered for at least 12 weeks

• requirement of RBC transfusions > 4 U in the previous 8 weeks

• Aged 18 years or more

• Adequate contraception, if relevant

• Negative pregnancy test if relevant

• Written Informed consent

• Ability to participate to a clinical trial and adhere to study procedures

• Health insurance

Exclusion Criteria:

• Therapy-related MDS (after chemo- or radiotherapy for a previous neoplasm or immune disorder)

• Patients with a planned allogeneic bone marrow transplantation

• Creatininemia >1.5 upper normal value or estimated Ccr less than 30ml/mn

• ALAT and ASAT >2.5 upper normal value

• Bilirubin >2N, except unconjugated hyperbilirubinemia due to MDS-related dyserythropoiesis

• Heart failure NYHA > II

• Known allergy to mannitol

• Other tumor, unstable for the last three years, except in situ uterine carcinoma or basal skin tumor

• ECOG > 2

• Life expectancy less than 3 months