Clinical trial NCT00469560: Safety, Tolerability, and Efficacy of Deferasirox in MDS
Official title: Open Label, Multicenter Study to Evaluate Safety/Tolerability and Efficacy of Deferasirox (ICL670) in Myelodysplastic Syndrome Patients With Chronic Transfusional Hemosiderosis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myelodysplastic Syndromes
Hemosiderosis
Keywords: MDS
Chronic transfusional hemosiderosis
Deferasirox
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2007-05-04
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: To evaluate the tolerability and safety profile of Deferasirox in pts with MDS with post-transfusional hemosiderosis
timeFrame: On a monthly basis thereafter from baseline assessment.
Secondary outcomes:
measure: To evaluate Deferasirox efficacy as chelation therapy in terms of reduction of serum ferritin levels compared to basal levels
timeFrame: At 3, 6, 9, and 12 months from baseline assessment.
measure: 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.
timeFrame: On a monthly basis thereafter from baseline assessment.
measure: Quality of Life evaluation.
timeFrame: At 3, 6, 9, and 12 months from baseline assessment.
measure: Compliance to chelating therapy evaluation.
timeFrame: On a monthly basis thereafter from baseline assessment.
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: SOC EMATOLOGIA ASO SS Antonio e Biagio
city: Bologna
country: Italy
facility: Ist.Ematologia e Oncologia Medica L.e A. Seragnoli
city: Cagliari
country: Italy
facility: CTMO-Ematologia Ospedale Binaghi
city: Cagliari
country: Italy
facility: Ospedale "A. Businco"
city: Caserta
country: Italy
facility: Oncoematologia "A.O.R.N. S'Anna e S.Sebastiano"
city: Castelfranco Veneto
country: Italy
facility: US Dipartimentale Centro per le Malattie del Sangue
city: Catania
country: Italy
facility: Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
city: Firenze
country: Italy
facility: Policlinico di Careggi, Università delgi studi di Firenze
city: Genova
country: Italy
facility: Clinica Ematologica - Università degli Studi
city: Napoli
country: Italy
facility: Divisione di Ematologia e TMO - Ospedale "A. Cardarelli "- Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
city: Perugia
country: Italy
facility: Clinica Ematol Università di Perugia, Policlinico Monteluce
city: Roma
country: Italy
facility: Ematologia- Università degli Studi "La Sapienza"
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore
city: Roma
country: Italy
facility: Università degli Studi di Tor Vergata
city: San Giovanni Rotondo
country: Italy
facility: Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
city: Siena
country: Italy
facility: U.O. Ematologia, Azienda Ospedaliera Universitaria Senese
city: Venezia
country: Italy
facility: Ospedale Civile SS. Giovanni e Paolo
Study officials:
affiliation: Ospedale "A. Businco", Cagliari
name: Emanuele ANGELUCCI, Pr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1093/jnci/85.5.365.
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.
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. doi: 10.1053/euhj.2001.2822.
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.
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. doi: 10.1200/JCO.2003.12.121.
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. doi: 10.1016/j.leukres.2006.05.015. Epub 2006 Jun 30.
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. doi: 10.1196/annals.1345.021.
citation: Efficace F, Santini V, La Nasa G, Cottone F, Finelli C, Borin L, Quaresmini G, Di Tucci AA, Volpe A, Cilloni D, Quarta G, Sanpaolo G, Rivellini F, Salvi F, Molteni A, Voso MT, Alimena G, Fenu S, Mandelli F, Angelucci E. Health-related quality of life in transfusion-dependent patients with myelodysplastic syndromes: a prospective study to assess the impact of iron chelation therapy. BMJ Support Palliat Care. 2016 Mar;6(1):80-8. doi: 10.1136/bmjspcare-2014-000726. Epub 2014 Sep 9.