Prospective, Multicenter, Open Label and Single-arm Study of Darbepoetin Alfa for Anemia in Myelodisplastic Syndrome Patients.

This study has been terminated.

(It was stopped due to a lack of recruitment after 48 patients included)

Sponsor:

Information provided by:

Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon

ClinicalTrials.gov Identifier:

NCT01039350

First received: December 23, 2009

Last updated: January 12, 2010

Last verified: January 2010

History of Changes

Purpose

Condition	Intervention	Phase
Myelodysplastic Syndrome	Drug: Darbepoetin alfa	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Prospective, Multicenter, Open Label and Single-arm Study of Darbepoetin Alfa for Anemia in Myelodisplastic Syndrome Patients.

Resource links provided by NLM:

MedlinePlus related topics: Anemia Myelodysplastic Syndromes

Drug Information available for: Darbepoetin Alfa

U.S. FDA Resources

Further study details as provided by Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon:

Primary Outcome Measures:

Proportion of patients achieving an erythroid response during the 24-week treatment period. [ Time Frame: weeks 8; 12; 16 and 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to erythroid response and time it is maintained. [ Time Frame: week 24 ] [ Designated as safety issue: No ]
Proportion of non-responders to darbepoetin alfa who obtain an erythroid response after the addition of Filgrastim [ Time Frame: weeks 8, 12, 16 and 24 ] [ Designated as safety issue: No ]
Proportion of patients receiving RBC transfusions (more than 1 unit) from week 5 to 24, inclusive [ Time Frame: weeks 8; 12; 16 and 24 ] [ Designated as safety issue: No ]
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. [ Time Frame: weeks 8; 16 and 24 ] [ Designated as safety issue: No ]
Number of morphological and cytogenetic disorders at baseline and end of treatment [ Time Frame: week 24 ] [ Designated as safety issue: No ]
Incidence of adverse events and serious adverse events [ Time Frame: weeks 8; 12; 16 and 24 ] [ Designated as safety issue: Yes ]
Proportion of patients with haemoglobin values over 12 g/dL at any time during the study [ Time Frame: weeks 8; 12; 16 and 24 ] [ Designated as safety issue: Yes ]

Enrollment:	80
Study Start Date:	February 2006
Estimated Study Completion Date:	July 2009
Estimated Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Intervention Details:

Darbepoetin alfa will be initiated at a weekly (QW) subcutaneous dose of 300 mcg over 8 weeks.

Other Name: Darbepoetin alfa

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).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01039350

Locations

Spain
Hospital Central de Asturias
Oviedo, Asturias, Spain, 33006
Hospital de Cruces
Barakaldo, Bilbao, Spain, 48903
Hospital Virgen del Puerto
Plasencia, Caceres, Spain, 10600
Hospital General Universitario de Alicante
Alicante, Spain, 03010
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Hospital Duran i Reynals
Barcelona, Spain, 08907
Hospital Vall D´Hebron
Barcelona, Spain, 08035
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital General Yagüe
Burgos, Spain, 09005
Hospital Universitario Puerta del Mar
Cádiz, Spain, 11009
Complejo Hospitalario Universitario Juan Canalejo
La Coruña, Spain, 15006
Hospital Universitario Doce de Octubre
Madrid, Spain, 28041
Hospital Ramón y Cajal
Madrid, Spain, 28034
Hospital Universitario de Salamanca
Salamanca, Spain, 37007
Hospital Arnau de Vilanova
Valencia, Spain, 46015
Hospital Universitario La Fé
Valencia, Spain, 46009

Sponsors and Collaborators

Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon

Investigators

Principal Investigator:

Ana M Villegas, MD

Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon

More Information

Publications:

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Nosslinger T, Reisner R, Koller E, Gruner H, Tuchler H, Nowotny H, Pittermann E, Pfeilstocker M. Myelodysplastic syndromes, from French-American-British to World Health Organization: comparison of classifications on 431 unselected patients from a single institution. Blood. 2001 Nov 15; 98(10): 2935-41.

Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079-88. Erratum in: Blood 1998 Feb 1;91(3):1100.

Littlewood TJ. Erythropoietin for the treatment of anemia associated with hematological malignancy. Hematol Oncol. 2001 Mar;19(1):19-30. Review.

Molldrem JJ, Leifer E, Bahceci E, Saunthararajah Y, Rivera M, Dunbar C, Liu J, Nakamura R, Young NS, Barrett AJ. Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndromes. Ann Intern Med. 2002 Aug 6;137(3):156-63. Summary for patients in: Ann Intern Med. 2002 Aug 6;137(3):I-27.

Raza A, Meyer P, Dutt D, Zorat F, Lisak L, Nascimben F, du Randt M, Kaspar C, Goldberg C, Loew J, Dar S, Gezer S, Venugopal P, Zeldis J. Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes. Blood. 2001 Aug 15;98(4):958-65.

Stasi R, Pagano A, Terzoli E, Amadori S. Recombinant human granulocyte-macrophage colony-stimulating factor plus erythropoietin for the treatment of cytopenias in patients with myelodysplastic syndromes. Br J Haematol. 1999 Apr;105(1):141-8.

Negrin RS, Stein R, Doherty K, Cornwell J, Vardiman J, Krantz S, Greenberg PL. Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood. 1996 May 15;87(10):4076-81.

Koury MJ, Bondurant MC. The molecular mechanism of erythropoietin action. Eur J Biochem. 1992 Dec 15;210(3):649-63. Review. No abstract available.

Rigolin GM, Porta MD, Bigoni R, Cavazzini F, Ciccone M, Bardi A, Cuneo A, Castoldi G. rHuEpo administration in patients with low-risk myelodysplastic syndromes: evaluation of erythroid precursors' response by fluorescence in situ hybridization on May-Grunwald-Giemsa-stained bone marrow samples. Br J Haematol. 2002 Dec;119(3):652-9.

Hellstrom-Lindberg E, Ahlgren T, Beguin Y, Carlsson M, Carneskog J, Dahl IM, Dybedal I, Grimfors G, Kanter-Lewensohn L, Linder O, Luthman M, Lofvenberg E, Nilsson-Ehle H, Samuelsson J, Tangen JM, Winqvist I, Oberg G, Osterborg A, Ost A. Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood. 1998 Jul 1;92(1):68-75.

Remacha AF, Arrizabalaga B, Villegas A, Manteiga R, Calvo T, Julia A, Fernandez Fuertes I, Gonzalez FA, Font L, Junca J, del Arco A, Malcorra JJ, Equiza EP, de Mendiguren BP, Romero M. Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group. Haematologica. 1999 Dec;84(12):1058-64.

Thompson JA, Gilliland DG, Prchal JT, Bennett JM, Larholt K, Nelson RA, Rose EH, Dugan MH. Effect of recombinant human erythropoietin combined with granulocyte/ macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS Study Group. Blood. 2000 Feb 15;95(4):1175-9.

Hast R, Wallvik J, Folin A, Bernell P, Stenke L. Long-term follow-up of 18 patients with myelodysplastic syndromes responding to recombinant erythropoietin treatment. Leuk Res. 2001 Jan;25(1):13-18.

[No authors listed] A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. Italian Cooperative Study Group for rHuEpo in Myelodysplastic Syndromes. Br J Haematol. 1998 Dec;103(4):1070-4.

Terpos E, Mougiou A, Kouraklis A, Chatzivassili A, Michalis E, Giannakoulas N, Manioudaki E, Lazaridou A, Bakaloudi V, Protopappa M, Liapi D, Grouzi E, Parharidou A, Symeonidis A, Kokkini G, Laoutaris NP, Vaipoulos G, Anagnostopoulos NI, Christakis JI, Meletis J, Bourantas KL, Zoumbos NC, Yataganas X, Viniou NA; For The Greek MDS Study Group. Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients. Br J Haematol. 2002 Jul;118(1):174-80.

Hellstrom-Lindberg E. Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. Br J Haematol. 1995 Jan;89(1):67-71.

Mantovani L, Lentini G, Hentschel B, Wickramanayake PD, Loeffler M, Diehl V, Tesch H. Treatment of anaemia in myelodysplastic syndromes with prolonged administration of recombinant human granulocyte colony-stimulating factor and erythropoietin. Br J Haematol. 2000 May;109(2):367-75.

Casadevall N, Durieux P, Dubois S, Hemery F, Lepage E, Quarre MC, Damaj G, Giraudier S, Guerci A, Laurent G, Dombret H, Chomienne C, Ribrag V, Stamatoullas A, Marie JP, Vekhoff A, Maloisel F, Navarro R, Dreyfus F, Fenaux P. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood. 2004 Jul 15;104(2):321-7. Epub 2004 Mar 30.

Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, Lowenberg B, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Gore S, Greenberg PL; World Health Organization(WHO) international working group. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000 Dec 1;96(12):3671-4.

Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G, Ahlgren T, Dahl IM, Dybedal I, Grimfors G, Hesse-Sundin E, Hjorth M, Kanter-Lewensohn L, Linder O, Luthman M, Lofvenberg E, Oberg G, Porwit-MacDonald A, Radlund A, Samuelsson J, Tangen JM, Winquist I, Wisloff F; Scandinavian MDS Group. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol. 2003 Mar;120(6):1037-46.

Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer. 2001 Apr;84 Suppl 1:3-10. Review.

Smith R. Applications of darbepoietin-alpha, a novel erythropoiesis-stimulating protein, in oncology. Curr Opin Hematol. 2002 May;9(3):228-33. Review.

Macdougall IC, Gray SJ, Elston O, Breen C, Jenkins B, Browne J, Egrie J. Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients. J Am Soc Nephrol. 1999 Nov;10(11):2392-5.

Kotasek D, Steger G, Faught W, Underhill C, Poulsen E, Colowick AB, Rossi G, Mackey J; Aranesp 980291 Study Group. Darbepoetin alfa administered every 3 weeks alleviates anaemia in patients with solid tumours receiving chemotherapy; results of a double-blind, placebo-controlled, randomised study. Eur J Cancer. 2003 Sep;39(14):2026-34.

Hellström-Lindberg E, Negrin R, Stein R, Krantz S, Lindberg G, Vardiman J, Ost A, Greenberg P. Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol. 1997 Nov;99(2):344-51.

Glaspy JA, Jadeja JS, Justice G, Kessler J, Richards D, Schwartzberg L, Tchekmedyian NS, Armstrong S, O'Byrne J, Rossi G, Colowick AB. Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy. Br J Cancer. 2002 Jul 29;87(3):268-76.

Musto P, Lanza F, Balleari E, Grossi A, Falcone A, Sanpaolo G, Bodenizza C, Scalzulli PR, La Sala A, Campioni D, Ghio R, Cascavilla N, Carella AM. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol. 2005 Jan;128(2):204-9.

Mannone L, Gardin C, Quarre MC, Bernard JF, Vassilieff D, Ades L, Park S, Vaultier S, Hamza F, Beyne-rauzy MO, Cheze S, Giraudier S, Agape P, Legros L, Voillat L, Dreyfus F, Fenaux P; Groupe Francais des Myelodysplasies. High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study. Br J Haematol. 2006 Jun;133(5):513-9.

Vansteenkiste J, Pirker R, Massuti B, Barata F, Font A, Fiegl M, Siena S, Gateley J, Tomita D, Colowick AB, Musil J; Aranesp 980297 Study Group. Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. J Natl Cancer Inst. 2002 Aug 21;94(16):1211-20.

Hedenus M, Adriansson M, San Miguel J, Kramer MH, Schipperus MR, Juvonen E, Taylor K, Belch A, Altés A, Martinelli G, Watson D, Matcham J, Rossi G, Littlewood TJ; Darbepoetin Alfa 20000161 Study Group. Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double-blind, placebo-controlled study. Br J Haematol. 2003 Aug;122(3):394-403.

Smith RE Jr, Tchekmedyian NS, Chan D, Meza LA, Northfelt DW, Patel R, Austin M, Colowick AB, Rossi G, Glaspy J. A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer. Br J Cancer. 2003 Jun 16;88(12):1851-8.

Verhoef GEG, Boogaerts MA. RHuEPO in the treatment of the myelodysplastic syndromes. In: Smyth JF, Boogaerts MA, Ehmer BR-M (eds): rHuEPO in cancer supportive treatment. Marcel Dekker, New York 1996;pp.13-34.

Glaspy J, Appelbaum S, Henry D et al. Effects of darbepoetin alfa (Aranesp®) timing with chemotherapy administration: a randomized study. SIOG 2003. Poster.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Villegas A, Arrizabalaga B, Fernández-Lago C, Castro M, Mayans JR, González-Porras JR, Duarte RF, Remacha AF, Luño E, Gasquet JA. Darbepoetin alfa for anemia in patients with low or intermediate-1 risk myelodysplastic syndromes and positive predictive factors of response. Curr Med Res Opin. 2011 May;27(5):951-60. Epub 2011 Mar 7.

Responsible Party:	Ana M Villegas, FEHH
ClinicalTrials.gov Identifier:	NCT01039350 History of Changes
Other Study ID Numbers:	GEE200401, 2005-002414-38
Study First Received:	December 23, 2009
Last Updated:	January 12, 2010
Health Authority:	Spain: Spanish Agency of Medicines

Keywords provided by Fundacion para el Estudio de la Hematologia y Hemoterapia en Aragon:

Myelodysplastic syndrome

Additional relevant MeSH terms:

Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms

Darbepoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013

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