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

Phase 2
Terminated
Conditions
Myelodysplastic Syndrome
Registration Number
NCT01039350
Lead Sponsor
Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Brief Summary

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

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).

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
80
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Proportion of patients achieving an erythroid response during the 24-week treatment period.weeks 8; 12; 16 and 24
Secondary Outcome Measures
NameTimeMethod
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 Filgrastimweeks 8, 12, 16 and 24
Proportion of patients receiving RBC transfusions (more than 1 unit) from week 5 to 24, inclusiveweeks 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 treatmentweek 24
Incidence of adverse events and serious adverse eventsweeks 8; 12; 16 and 24
Proportion of patients with haemoglobin values over 12 g/dL at any time during the studyweeks 8; 12; 16 and 24

Trial Locations

Locations (16)

Hospital de Cruces

🇪🇸

Barakaldo, Bilbao, Spain

Hospital Virgen del Puerto

🇪🇸

Plasencia, Caceres, Spain

Hospital General Universitario de Alicante

🇪🇸

Alicante, Spain

Hospital Central de Asturias

🇪🇸

Oviedo, Asturias, Spain

Hospital Duran i Reynals

🇪🇸

Barcelona, Spain

Hospital Ramón y Cajal

🇪🇸

Madrid, Spain

Hospital General Yagüe

🇪🇸

Burgos, Spain

Hospital de la Santa Creu i Sant Pau

🇪🇸

Barcelona, Spain

Hospital Vall D´Hebron

🇪🇸

Barcelona, Spain

Hospital Clinic i Provincial de Barcelona

🇪🇸

Barcelona, Spain

Hospital Universitario Doce de Octubre

🇪🇸

Madrid, Spain

Hospital Universitario Puerta del Mar

🇪🇸

Cádiz, Spain

Complejo Hospitalario Universitario Juan Canalejo

🇪🇸

La Coruña, Spain

Hospital Universitario La Fé

🇪🇸

Valencia, Spain

Hospital Universitario de Salamanca

🇪🇸

Salamanca, Spain

Hospital Arnau de Vilanova

🇪🇸

Valencia, Spain

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