Darbepoetin Alpha in Myelodysplastic Syndromes (MDS)

Phase 2

• Conditions: Myelodysplastic Syndromes

• Registration Number: NCT00443339
• Lead Sponsor: Groupe Francophone des Myelodysplasies

Brief Summary

This is an evaluation of the effectiveness of darbepoetin alpha in treating anemia of MDS patients with an International Prognostic Scoring System (IPSS) score of low or intermediate 1.

Detailed Description

Inclusion of MDS with IPSS low or int-1 and hemoglobin \< 10/dL.

Study drug: Darbepoetin alfa (Aranesp) 500 microg every two weeks subcutaneously during 12 weeks, combined to filgrastim 300 microg twice weekly for an additional 12 weeks in non responders.

Response will be evaluated at 12 weeks. Patients with major or minor erythroid response (HI-E major or minor according to IWG 2000 criteria) will be continued on Aranesp. In non-responders, an additional 12 weeks of Aranesp at the same dosing, combined to Filgrastim (300 ug twice weekly, then adjusted to maintain WBC between 5000 and 10000/mm3) will be proposed. In case of response, the treatment will be continued for a total duration of 24 months. If Hb level reaches levels \> 13 g/dl at any time, Aranesp should be discontinued until Hb levels are less than 12 g/dl. Aranesp should then be resumed at 500 µg/injection every 3 weeks. Intervals between injections should be further increased by one week every time they lead to Hb levels \> 13 g/dl. The purpose of this dose adjustment is to reach the Aranesp schedule allowing a maintenance Hb level between 11 and 12 g/dl.

Study Timeline

• Study Start: 2006-12
• Status Verified: 2007-03
• Study First Submitted: 2007-03-04
• Study First Submitted QC: 2007-03-04
• Study First Posted: 2007-03-06
• Last Update Submitted: 2007-05-15
• Last Update Posted: 2007-05-17
• Study Completion: 2008-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 99

Inclusion Criteria

• MDS of the following subtypes:

  • RA, RAS, RAEB with marrow blasts < 10% (according to FAB),
  • RA, RARS, RCMD, RAEB 1, CMML 1 with ≤ 10% WBC counts < 13000/mm3 (according to WHO classification)

• Anemia, defined by Hb < 10 g/dl or RBC transfusion requirement in the absence of other causes of anemia (especially renal failure, iron, or folate deficiency)

• IPSS ≤ 1(ie IPSS low or intermediate 1)

• EPO level < 500 UI/L

• Ability to perform physical tests of exercise tolerance

• No renal failure (creatinine ≤ 120% normal upper value for the center)

• No underlying severe condition

• ECOG performance status score of 0, 1, or 2

• Must be 18 years of age or older at the time of screening

• Written informed consent

Exclusion Criteria

• Therapy related MDS
• MDS with IPSS > 1 (int 2 or high score)
• Chronic myelomonocytic leukemia with > 10% marrow blasts or WBC > 13000/mm3
• Uncontrolled systemic hypertension
• Cardiac condition: uncontrolled angina, congestive heart failure, or uncontrolled cardiac arrhythmia
• Creatinine level > 120% upper normal value for the center.
• Clinically significant systemic infection or chronic inflammatory disease (eg, rheumatoid arthritis) present at the time of screening
• Serum folate ≤ 2.0 ng/mL or vitamin B12 ≤ 200 pg/mL (anemia related to nutritional deficiencies)
• Other causes of anemia (eg, hemolysis, bleeding, sickle cell anemia, renal disease)
• Pregnant (ie, positive βhCG test) or breast feeding female subjects
• Women of childbearing potential and not using adequate contraceptives
• Known positive antibody response to an erythropoietic growth factor
• Known hypersensitivity to darbepoetin alpha or any of its excipients, or to recombinant erythropoietins
• Patient unable to understand the protocol or to be adequately followed up.
• History of seizures
• Previous history of thrombotic events
• Concomitant treatment with thalidomide

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Erythroid response at 12 weeks according to IWG 2000 (major and minor hematologic improvement) and IWG 2006 criteria

Secondary Outcome Measures

Name	Time	Method
Tolerability and safety of darbepoetin alpha
Rate of progression to more severe MDS, with higher IPSS (int 2 or high), or to AML during the treatment and follow-up periods
Overall survival
Quality of life during the study, using the FACT-An and SF36 questionnaires by comparison to pre-treatment values
Overall physical performance as measured by VO2max, 6 minute walk test and the "short physical performance battery" test

Trial Locations

Locations (27)

CHU d'Avignon; 🇫🇷 Avignon, France

Hopital Percy; 🇫🇷 Clamart, France

CHU de Caen; 🇫🇷 Caen, France

CHRU Hurriez; 🇫🇷 Lille, France

Hopital St Louis; 🇫🇷 Paris, France

CHU Robert Debre; 🇫🇷 Reims, France

Hopital Henri Becquerel; 🇫🇷 Rouen, France

CHU d'Amiens; 🇫🇷 Amiens, France

CHU d'Angers; 🇫🇷 Angers, France

CHU de Brest - Hopital Morvan; 🇫🇷 Brest, France

CHU Albert Michallon; 🇫🇷 Grenoble, France

CHU Pontchaillou; 🇫🇷 Rennes, France

CHU Nancy-Brabois; 🇫🇷 Vandoeuvre les Nancy, France

Hopital Purpan; 🇫🇷 Toulouse, France

CH de la Cote Basque; 🇫🇷 Bayonne, France

Hopital Paoli Calmette; 🇫🇷 Marseille, France

Hopital Jean-Bernard; 🇫🇷 Poitiers, France

Hopital Hautepierre; 🇫🇷 Strasbourg, France

Hopital Henri Mondor; 🇫🇷 Créteil, France

CHU Archet; 🇫🇷 Nice, France

Hopital Saint Antoine; 🇫🇷 Paris, France

Hopital Edouard Herriot; 🇫🇷 Lyon, France

CHRU Limoges; 🇫🇷 Limoges, France

CHU de Dijon; 🇫🇷 Dijon, France

Hopital Cochin; 🇫🇷 Paris, France

Hopital Hotel Dieu; 🇫🇷 Paris, France

Hopital Bretonneau; 🇫🇷 Tours, France