Clinical trial NCT00443339: Darbepoetin Alpha in Myelodysplastic Syndromes (MDS)
Official title: A Phase II Study of Darbepoetin Alpha in Myelodysplastic Syndromes (MSD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: Myelodysplastic syndromes with IPSS Low or Int-1
Anemia
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
First posted: 2007-03-06
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Erythroid response at 12 weeks according to IWG 2000 (major and minor hematologic improvement) and IWG 2006 criteria
Secondary outcomes:
measure: Tolerability and safety of darbepoetin alpha
measure: Rate of progression to more severe MDS, with higher IPSS (int 2 or high), or to AML during the treatment and follow-up periods
measure: Overall survival
measure: Quality of life during the study, using the FACT-An and SF36 questionnaires by comparison to pre-treatment values
measure: Overall physical performance as measured by VO2max, 6 minute walk test and the "short physical performance battery" test
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens
city: Angers
country: France
facility: CHU d'Angers
city: Avignon
country: France
facility: CHU d'Avignon
city: Bayonne
country: France
facility: CH de la Cote Basque
city: Brest
country: France
facility: CHU de Brest - Hopital Morvan
city: Caen
country: France
facility: CHU de Caen
city: Clamart
country: France
facility: Hopital Percy
city: Créteil
country: France
facility: Hopital Henri Mondor
city: Dijon
country: France
facility: CHU de Dijon
city: Grenoble
country: France
facility: CHU Albert Michallon
city: Lille
country: France
facility: CHRU Hurriez
city: Limoges
country: France
facility: CHRU Limoges
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Marseille
country: France
facility: Hopital Paoli Calmette
city: Nantes
country: France
facility: Hopital Hotel Dieu
city: Nice
country: France
facility: CHU Archet
city: Paris
country: France
facility: Hopital Hotel Dieu
city: Paris
country: France
facility: Hopital Hotel Dieu
city: Paris
country: France
facility: Hopital St Louis
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: Hopital Cochin
city: Poitiers
country: France
facility: Hopital Jean-Bernard
city: Reims
country: France
facility: CHU Robert Debre
city: Rennes
country: France
facility: CHU Pontchaillou
city: Rouen
country: France
facility: Hopital Henri Becquerel
city: Strasbourg
country: France
facility: Hopital Hautepierre
city: Toulouse
country: France
facility: Hopital Purpan
city: Tours
country: France
facility: Hopital Bretonneau
city: Vandoeuvre les Nancy
country: France
facility: CHU Nancy-Brabois
Study officials:
affiliation: Groupe Francophone des Myelodysplasies
name: Charikleia KELAIDI, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kelaidi C, Beyne-Rauzy O, Braun T, Sapena R, Cougoul P, Ades L, Pillard F, Lamberto C, Charniot JC, Guerci A, Choufi B, Stamatoullas A, Slama B, De Renzis B, Ame S, Damaj G, Boyer F, Chaury MP, Legros L, Cheze S, Testu A, Gyan E, Bene MC, Rose C, Dreyfus F, Fenaux P. High response rate and improved exercise capacity and quality of life with a new regimen of darbepoetin alfa with or without filgrastim in lower-risk myelodysplastic syndromes: a phase II study by the GFM. Ann Hematol. 2013 May;92(5):621-31. doi: 10.1007/s00277-013-1686-4. Epub 2013 Jan 29.