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).

Eligibility Criteria:
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