Prospective, Multicenter, Open Label and Single-arm Study of Darbepoetin Alfa for Anemia in Myelodisplastic Syndrome Patients.

Prospective, Multicenter, Open Label and Single-arm Study of Darbepoetin Alfa for Anemia in Myelodisplastic Syndrome Patients.

This is an open-label, single-arm, multicentre, prospective study of darbepoetin alfa to treat anaemia in patients with low and intermediate-1 IPSS risk MDS. The study will consist of a 14-day screening period followed by a maximum 24-week treatment period and a final visit.

This is an open-label, single-arm, multicentre, prospective study of darbepoetin alfa to treat anaemia in patients with low and intermediate-1 IPSS risk MDS. The study will consist of a 14-day screening period followed by a maximum 24-week treatment period and a final visit. Darbepoetin alfa will be initiated at a dose of 300 mcg QW SC over a period of 8 weeks. After 8 weeks, erythroid response will be evaluated, and treatment algorithm adapted to it.

The study treatment period will last for a maximum of 24 weeks. The treatment will end at the start of week 24. If the scheduled 24-week treatment period is not completed, it will end during the week of the last administration of the study drug.

The follow-up period will last for a minimum of 4 weeks and a maximum of 8 weeks after the last dose of darbepoetin alfa.

Subjects will be stratified at enrolment according to IPSS (low risk versus intermediate-1 risk).

Inclusion Criteria:

• Age ³ 18 years
• Low or intermediate-1 risk MDS according to IPSS, and FAB classification of RA, RARS, or RAEB with blasts £ 10%
• Predictive variables of good response (serum erythropoietin levels < 500 IU/l and transfusion requirements < 2 packed RBC/month over the preceding 2 months)
• Anaemia (Hb £ 10 g/dL), confirmed in the 14 days before day 1 of the study
• Life expectancy of at least 6 months
• ECOG Performance status score of 0, 1, or 2
• Subject must sign and date the Informed Consent (approved by a Clinical Research Ethics Committee - CREC), before any study-specific procedure is performed

Exclusion Criteria:

• Known history of convulsive disorders
• Poorly controlled hypertension (diastolic blood pressure > 100 mmHg) at screening
• Inadequate liver function (total bilirubin > two times the upper limit of the normal range (ULN), and liver enzymes (ALT, AST) > two times ULN)
• Inadequate renal function (serum creatinine concentration > 2 mg/dL)
• Ferritin < 100 ng/ml or transferrin saturation index (TSI) < 16%; Vitamin B12 deficiency (< 200 pg/ml) or folate deficiency (< 2 ng/ml)
• Clinically-relevant haemorrhages
• Haemolytic anaemia
• Cardiac condition: uncontrolled angina, congestive heart failure, or uncontrolled cardiac arrhythmia
• Clinically significant systemic infection or chronic inflammatory disease present at time of screening
• Any concomitant therapy used to treat MDS (including other growth factors than those described as part of this protocol, chemotherapy, antibody-based cancer treatment, hormonal therapy, interferon, and interleukins)
• Treatment with rHuEPO or darbepoetin alfa over the 4 weeks prior to Day 1 of the study
• More than 2 RBC transfusions over the 28 days prior to Day 1 of the study
• Pregnant or breast feeding women
• Subjects of childbearing-potential who do not take adequate contraceptive measures, in the opinion of the investigator
• Known hypersensitivity to any mammal-derived recombinant product