Myelodysplastic Syndrome
Conditions
Keywords
Myelodysplastic syndrome
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).
Interventions
DRUGDarbepoetin alfa
Darbepoetin alfa will be initiated at a weekly (QW) subcutaneous dose of 300 mcg over 8 weeks.
Sponsors
Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients achieving an erythroid response during the 24-week treatment period. | weeks 8; 12; 16 and 24 |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of adverse events and serious adverse events | weeks 8; 12; 16 and 24 |
| 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 |
| Proportion of patients with haemoglobin values over 12 g/dL at any time during the study | weeks 8; 12; 16 and 24 |
Countries
Spain
Outcome results
None listed