Darbepoetin Alpha in Myelodysplastic Syndromes (MDS)

Myelodysplastic Syndromes Clinical Trial

Official title:

A Phase II Study of Darbepoetin Alpha in Myelodysplastic Syndromes (MSD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00443339
• Other study ID #: GFM-DAR500-2006-01
• Status: Recruiting
• Phase: Phase 2
• First received: March 4, 2007
• Last updated: May 15, 2007
• Start date: December 2006
• Est. completion date: July 2008

Study information

• Verified date: March 2007
• Source: Groupe Francophone des Myelodysplasies
• Contact: Charikleia KELAIDI, MD
• Phone: 0033148957051
• Email: charikleia .kelaidi[@]avc.aphp.fr
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 99
• Est. completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 ßhCG 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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Darbepoetin

Locations

Country	Name	City	State
France	CHU d'Amiens	Amiens
France	CHU d'Angers	Angers
France	CHU d'Avignon	Avignon
France	CH de la Cote Basque	Bayonne
France	CHU de Brest - Hopital Morvan	Brest
France	CHU de Caen	Caen
France	Hopital Percy	Clamart
France	Hopital Henri Mondor	Créteil
France	CHU de Dijon	Dijon
France	CHU Albert Michallon	Grenoble
France	CHRU Hurriez	Lille
France	CHRU Limoges	Limoges
France	Hopital Edouard Herriot	Lyon
France	Hopital Paoli Calmette	Marseille
France	Hopital Hotel Dieu	Nantes
France	CHU Archet	Nice
France	Hopital Cochin	Paris
France	Hopital Hotel Dieu	Paris
France	Hopital Hotel Dieu	Paris
France	Hopital Saint Antoine	Paris
France	Hopital St Louis	Paris
France	Hopital Jean-Bernard	Poitiers
France	CHU Robert Debre	Reims
France	CHU Pontchaillou	Rennes
France	Hopital Henri Becquerel	Rouen
France	Hopital Hautepierre	Strasbourg
France	Hopital Purpan	Toulouse
France	Hopital Bretonneau	Tours
France	CHU Nancy-Brabois	Vandoeuvre les Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Groupe Francophone des Myelodysplasies

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Erythroid response at 12 weeks according to IWG 2000 (major and minor hematologic improvement) and IWG 2006 criteria
Secondary	Tolerability and safety of darbepoetin alpha
Secondary	Rate of progression to more severe MDS, with higher IPSS (int 2 or high), or to AML during the treatment and follow-up periods
Secondary	Overall survival
Secondary	Quality of life during the study, using the FACT-An and SF36 questionnaires by comparison to pre-treatment values
Secondary	Overall physical performance as measured by VO2max, 6 minute walk test and the “short physical performance battery” test