Safety, Tolerability, and Efficacy of Deferasirox in MDS

Myelodysplastic Syndromes Clinical Trial

Official title:

Open Label, Multicenter Study to Evaluate Safety/Tolerability and Efficacy of Deferasirox (ICL670) in Myelodysplastic Syndrome Patients With Chronic Transfusional Hemosiderosis.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00469560
• Other study ID #: MDS0306
• Status: Completed
• Phase: Phase 3
• First received: May 3, 2007
• Last updated: November 21, 2016
• Start date: June 2007
• Est. completion date: November 2013

Study information

• Verified date: November 2016
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open label, single arm study on Deferasirox treatment in MDS patients with chronic transfusional hemosiderosis.

Patients receive daily oral dosis of Deferasirox in order to eliminate the quantity of iron administered during transfusions and, if needed, to reduce the overload of already present iron.

After an screening phase in which patients are evaluated according to eligibility criteria, a one year treatment phase foresees monthly visits to evaluate safety and efficacy signs.

Description:

It has been widely shown that an appropriate chelating therapy in chronic anemias transfusion dependent can prevent the overstock of iron and can reduce the already existing overstock reducing, then, the co-morbidity and improving survival.

In particular, some authors have shown in MDS affected patients undergoing intensive chelating therapy with deferoxamine haematological recovery with a reduction of the need of transfusions.

With the present study, we plan to evaluate the safety and efficacy of a therapy with the new oral chelating Deferasirox in MDS patients with transfusional hemosiderosis.

This is an open label, single arm study on Deferasirox treatment in MDS patients with chronic transfusional hemosiderosis.

Patients will receive daily oral dosis of Deferasirox in order to eliminate the quantity of iron administered during transfusions and, if needed, to reduce the overload of already present iron.

After an screening phase in which patients are evaluated according to eligibility criteria, a one year treatment phase foresees monthly visits to evaluate safety and efficacy signs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 158
• Est. completion date: November 2013
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients, both males and females, with low and intermediate I risk (IPSS score) Myelodysplastic syndrome and transfusion-induced hemosiderosis.

• Age >=18 years

• Patients who never received chelation therapy or who received a therapy with Desferal after a day of wash out

• Medical history of at least 20 blood transfusions (equivalent to 100 ml/kg of red cells concentrate).

• Availability of data concerning blood transfusions during the 12 weeks before screening

• Serum ferritin >= 1000 µg/L at least twice (at least 2 week interval between the 2 analysis) during the year before the screening

• Life expectancy > 12 months

• Availability of at least 3 complete blood counts (before transfusions) during the 12 weeks before the screening

Exclusion Criteria:

• Diagnosis different from MDS (i.e. myelofibrosis)

• Severe renal impairment (creatinine clearance < 60 ml/min)

• ALT/AST > 500 U/L

• Active B and/or C hepatitis

• Patients treated during the past 4 weeks with experimental drugs for MDS (including thalidomide, azacitidine, arsenic trioxide). These patients become eligible after a "wash out" of at least 4 weeks

• Concomitant treatment with another iron-chelating agent

Related Conditions & MeSH terms

• Hemosiderosis
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Deferasirox

Locations

Country	Name	City	State
Italy	SOC EMATOLOGIA ASO SS Antonio e Biagio	Alessandria
Italy	Ist.Ematologia e Oncologia Medica L.e A. Seragnoli	Bologna
Italy	CTMO-Ematologia Ospedale Binaghi	Cagliari
Italy	Ospedale "A. Businco"	Cagliari
Italy	Oncoematologia "A.O.R.N. S'Anna e S.Sebastiano"	Caserta
Italy	US Dipartimentale Centro per le Malattie del Sangue	Castelfranco Veneto
Italy	Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"	Catania
Italy	Policlinico di Careggi, Università delgi studi di Firenze	Firenze
Italy	Clinica Ematologica - Università degli Studi	Genova
Italy	Divisione di Ematologia e TMO - Ospedale "A. Cardarelli "- Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"	Napoli
Italy	Clinica Ematol Università di Perugia, Policlinico Monteluce	Perugia
Italy	Ematologia- Università degli Studi "La Sapienza"	Roma
Italy	Università Cattolica del Sacro Cuore	Roma
Italy	Università degli Studi di Tor Vergata	Roma
Italy	Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo
Italy	U.O. Ematologia, Azienda Ospedaliera Universitaria Senese	Siena
Italy	Ospedale Civile SS. Giovanni e Paolo	Venezia

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

References & Publications (7)

Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. — View Citation

Alessandrino EP, Amadori S, Barosi G, Cazzola M, Grossi A, Liberato LN, Locatelli F, Marchetti M, Morra E, Rebulla P, Visani G, Tura S; Italian Society of Hematology. Evidence- and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology. Haematologica. 2002 Dec;87(12):1286-306. — View Citation

Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, Firmin DN, Wonke B, Porter J, Walker JM, Pennell DJ. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J. 2001 Dec;22(23):2171-9. — View Citation

Borgna-Pignatti C, Franchini M, Gandini G, Vassanelli A, De Gironcoli M, Aprili G. Subcutaneous bolus injection of deferoxamine in adult patients affected by onco-hematologic diseases and iron overload. Haematologica. 1998 Sep;83(9):788-90. — View Citation

Caocci G, Baccoli R, Ledda A, Littera R, La Nasa G. A mathematical model for the evaluation of amplitude of hemoglobin fluctuations in elderly anemic patients affected by myelodysplastic syndromes: correlation with quality of life and fatigue. Leuk Res. 2007 Feb;31(2):249-52. Epub 2006 Jun 30. — View Citation

Efficace F, Bottomley A, Osoba D, Gotay C, Flechtner H, D'haese S, Zurlo A. Beyond the development of health-related quality-of-life (HRQOL) measures: a checklist for evaluating HRQOL outcomes in cancer clinical trials--does HRQOL evaluation in prostate cancer research inform clinical decision making? J Clin Oncol. 2003 Sep 15;21(18):3502-11. — View Citation

Galanello R. Evaluation of ICL670, a once-daily oral iron chelator in a phase III clinical trial of beta-thalassemia patients with transfusional iron overload. Ann N Y Acad Sci. 2005;1054:183-5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the tolerability and safety profile of Deferasirox in pts with MDS with post-transfusional hemosiderosis		On a monthly basis thereafter from baseline assessment.
Secondary	To evaluate Deferasirox efficacy as chelation therapy in terms of reduction of serum ferritin levels compared to basal levels		At 3, 6, 9, and 12 months from baseline assessment.
Secondary	To evaluate the impact Deferasirox iron chelating therapy vs the normal demand of transfusions in a subgroup of pts that will not receive growth factors or chemotherapy according to their basal characteristics.		On a monthly basis thereafter from baseline assessment.
Secondary	Quality of Life evaluation.		At 3, 6, 9, and 12 months from baseline assessment.
Secondary	Compliance to chelating therapy evaluation.		On a monthly basis thereafter from baseline assessment.