Safety, Tolerability, and Efficacy of Deferasirox in MDS

NCT00469560 | Completed Phase 3

• 1 other identifier: MDS0306
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 17

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.

Conditions

Myelodysplastic Syndromes; Hemosiderosis

Keywords

MDS; Chronic transfusional hemosiderosis; Deferasirox

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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.

• 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.

• Quality of Life evaluation.

  At 3, 6, 9, and 12 months from baseline assessment.

• Compliance to chelating therapy evaluation.

  On a monthly basis thereafter from baseline assessment.

Study Arms (1)

Deferasirox

EXPERIMENTAL

Drug: Deferasirox

Interventions

Deferasirox DRUG

Deferasirox

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (17)

SOC EMATOLOGIA ASO SS Antonio e Biagio

Alessandria, Italy

Location

Ist.Ematologia e Oncologia Medica L.e A. Seragnoli

Bologna, Italy

Location

CTMO-Ematologia Ospedale Binaghi

Cagliari, Italy

Location

Ospedale "A. Businco"

Cagliari, Italy

Location

Oncoematologia "A.O.R.N. S'Anna e S.Sebastiano"

Caserta, Italy

Location

US Dipartimentale Centro per le Malattie del Sangue

Castelfranco Veneto, Italy

Location

Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"

Catania, Italy

Location

Policlinico di Careggi, Università delgi studi di Firenze

Florence, Italy

Location

Clinica Ematologica - Università degli Studi

Genova, Italy

Location

Divisione di Ematologia e TMO - Ospedale "A. Cardarelli "- Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

Napoli, Italy

Location

Clinica Ematol Università di Perugia, Policlinico Monteluce

Perugia, Italy

Location

Ematologia- Università degli Studi "La Sapienza"

Roma, Italy

Location

Università Cattolica del Sacro Cuore

Roma, Italy

Location

Università degli Studi di Tor Vergata

Roma, Italy

Location

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

U.O. Ematologia, Azienda Ospedaliera Universitaria Senese

Siena, Italy

Location

Ospedale Civile SS. Giovanni e Paolo

Venezia, Italy

Location

Related Publications (8)

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  PMID: 8433390 BACKGROUND

• 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.

  PMID: 12495903 BACKGROUND

• 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.

  PMID: 11913479 BACKGROUND

• 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.

  PMID: 9825575 BACKGROUND

• 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.

  PMID: 12972527 BACKGROUND

• 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.

  PMID: 16814382 BACKGROUND

• 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.

  PMID: 16339664 BACKGROUND

• 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.

  PMID: 25204541 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Hemosiderosis

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Overload; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Emanuele ANGELUCCI, Pr.

  Ospedale "A. Businco", Cagliari

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2007
• First Posted: May 4, 2007
• Study Start: June 1, 2007
• Primary Completion: March 1, 2010
• Study Completion: November 1, 2013
• Last Updated: November 22, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (17)