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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Darbepoetin alfa


Participation Criteria
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Eligibility Criteria
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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

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Darbepoetin alfa|Darbepoetin alfa will be initiated at a weekly (QW) subcutaneous dose of 300 mcg over 8 weeks.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving an erythroid response during the 24-week treatment period. |  | weeks 8; 12; 16 and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to erythroid response and time it is maintained. |  | week 24 | 
| Proportion of non-responders to darbepoetin alfa who obtain an erythroid response after the addition of Filgrastim |  | weeks 8, 12, 16 and 24 | 
| Proportion of patients receiving RBC transfusions (more than 1 unit) from week 5 to 24, inclusive |  | weeks 8; 12; 16 and 24 | 
| Score changes in the FACT-Fatigue quality-of-life scale between the baseline visit, and weeks 8, 16, 24, and the end of the study. |  | weeks 8; 16 and 24 | 
| Number of morphological and cytogenetic disorders at baseline and end of treatment |  | week 24 | 
| Incidence of adverse events and serious adverse events |  | weeks 8; 12; 16 and 24 | 
| Proportion of patients with haemoglobin values over 12 g/dL at any time during the study |  | weeks 8; 12; 16 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic syndrome