Darbepoetin Alpha in Myelodysplastic Syndromes (MDS)

Sponsor

Groupe Francophone des Myelodysplasies (Other)

Overall Status

Unknown status

CT.gov ID

NCT00443339

Collaborator

(none)

Enrollment

Locations

Duration (Months)

3.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: Darbepoetin	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

99 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2006

Anticipated Study Completion Date :

Jul 1, 2008

Outcome Measures

Primary Outcome Measures

Erythroid response at 12 weeks according to IWG 2000 (major and minor hematologic improvement) and IWG 2006 criteria []

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU d'Amiens	Amiens	France	800054
2	CHU d'Angers	Angers	France	43033
3	CHU d'Avignon	Avignon	France	84000
4	CH de la Cote Basque	Bayonne	France	64 100
5	CHU de Brest - Hopital Morvan	Brest	France	29 609
6	CHU de Caen	Caen	France	14033
7	Hopital Percy	Clamart	France	92140
8	Hopital Henri Mondor	Créteil	France	94010
9	CHU de Dijon	Dijon	France	21034
10	CHU Albert Michallon	Grenoble	France	38043
11	CHRU Hurriez	Lille	France	59057
12	CHRU Limoges	Limoges	France	87046
13	Hopital Edouard Herriot	Lyon	France	69437
14	Hopital Paoli Calmette	Marseille	France	13273
15	Hopital Hotel Dieu	Nantes	France	44093
16	CHU Archet	Nice	France	06202
17	Hopital Hotel Dieu	Paris	France	75181
18	Hopital Hotel Dieu	Paris	France	75181
19	Hopital St Louis	Paris	France	75475
20	Hopital Saint Antoine	Paris	France	75571
21	Hopital Cochin	Paris	France	75679
22	Hopital Jean-Bernard	Poitiers	France	86021
23	CHU Robert Debre	Reims	France	51092
24	CHU Pontchaillou	Rennes	France	35033
25	Hopital Henri Becquerel	Rouen	France	76038
26	Hopital Hautepierre	Strasbourg	France	67098
27	Hopital Purpan	Toulouse	France	31031
28	Hopital Bretonneau	Tours	France	37044
29	CHU Nancy-Brabois	Vandoeuvre les Nancy	France	54511