A Study Assessing the Efficacy and Safety of Deferasirox in Patients With Transfusion-dependent Iron Overload

NCT00171821 | Completed Phase 3

• 2 other identifiers: CICL670A24092004-003953-16
• Study Type: interventional
• Target: 1,784
• Locations: 22 countries
• Sites: 94

Brief Summary

This study uses a single arm, multi-center, open-label trial design. The study will assess the efficacy and safety of 52 weeks of treatment with deferasirox (ICL670) in patients with evidence of transfusion induced iron overload.

Conditions

Transfusion-dependent Iron Overload

Keywords

Thalassemia; Myelodysplastic Syndrome; MDS; Sickle cell; Diamond-Blackfan anemia; Transfusion; Anemia; Fanconi; Chelation; Deferasirox

Outcome Measures

Primary Outcomes (1)

• To evaluate if fixed starting doses of ICL670, based on transfusion history and subsequent dose titration can provide clinically acceptable chelation as measured by serum ferritin

  at baseline and at 52 weeks

Secondary Outcomes (3)

• To evaluate the safety and tolerability profile of in patients treated for up to 52 weeks

  Monthly

• Evaluate efficacy, tolerabilty and safety in the subgroup of patients with baseline LIC < 7 mg Fe/g dw

  Monthly

• Evaluate the relationship between serum ferritin and potential surrogate markers

  Monthly

Study Arms (1)

ICL670 (Deferasirox)

EXPERIMENTAL

Drug: Deferasirox

Interventions

Deferasirox DRUG

Also known as: ICL670

ICL670 (Deferasirox)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients presenting with transfusion-dependent anemias (independent of underlying condition) with transfusional iron overload as shown by a serum ferritin level of ≥ 1000 ng/ml
• Patients of either gender and aged ≥ 2 years
• Female patients who have reached menarche and who are sexually active must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation.
• Written informed consent by the patient
• The definition of the term "pediatric" will be in accordance with local legislation. Parents or legal guardians will be fully informed by the investigator as to the requirements of the study. The pediatric patients themselves will be informed according to their capabilities in a language and terms that they are able to understand. Written informed consent will be obtained from their parents or legal guardians on the patient's behalf in accordance with the national legislation. If capable, all patients should also personally sign their written informed assent.

You may not qualify if:

• Non-transfusional hemosiderosis
• Patients with clinical evidence supporting the need for intensive chelation, based on the investigator's judgment
• Patients with mean levels of alanine aminotransferase (ALT) \> 300 U/l
• Patients with uncontrolled systemic hypertension
• Patients with serum creatinine above the upper limit of normal (ULN)
• Significant proteinuria as indicated by a urinary protein/creatinine ratio \> 0.5 (mg/mg) in second-voiding urine samples taken at both visits 1 and 2. A third sample is to be taken from patients in whom one ratio is \> 0.5 (mg/mg) and one is ≤ 0.5 (mg/mg) and patients in whom the urinary protein/creatinine ratio is \> 0.5 (mg/mg) in two of the three determinations are also to be excluded.
• History of nephrotic syndrome
• Patients with 3rd atrioventricular (A-V) block, clinically relevant Q-T interval prolongation as well as patients requiring treatment with digoxin and similar compounds or drugs which may induce prolongation of the Q-T interval
• Patients with a previous history of clinically relevant ocular toxicity related to iron chelation
• Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent the patient from undergoing study treatment
• Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment
• Pregnant or breast feeding patients
• Patients treated with systemic investigational drugs within the past 4 weeks or topical investigational drugs within the past 7 days
• Any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following:
• history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (97)

Novartis Investigative Site

Adelaide, Australia

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Camperdown, Australia

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Clayton, Australia

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Melbourne, Australia

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Perth, Australia

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South Brisbane, Australia

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Westmead, Australia

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Graz, Austria

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Linz, Austria

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Vienna, Austria

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Brussels, Belgium

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Ghent, Belgium

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Godinne, Belgium

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La Louvière, Belgium

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Leuven, Belgium

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Guangzhou, China

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Nanjing, China

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Shanghai, China

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Aarhus, Denmark

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Copenhagen, Denmark

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Herlev, Denmark

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Hillerød, Denmark

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Cairo, Egypt

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Angers, France

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Avignon, France

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Bobigny, France

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Créteil, France

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Lille, France

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Lyon, France

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Nice, France

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Paris, France

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Pessac, France

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Rennes, France

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Toulouse, France

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Vandœuvre-lès-Nancy, France

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Augsburg, Germany

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Braunschweig, Germany

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Dresden, Germany

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Düsseldorf, Germany

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Frankfurt, Germany

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Frankfurt am Main, Germany

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Frieburg, Germany

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Göttingen, Germany

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Greifswald, Germany

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Hanover, Germany

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Mainz, Germany

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München, Germany

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Ulm, Germany

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Athens, Greece

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Larissa, Greece

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Pátrai, Greece

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Thessaloniki, Greece

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Hong Kong, Hong Kong

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Afula, Israel

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Jerusalem, Israel

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Petah Tikva, Israel

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Bologna, Italy

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Brindisi, Italy

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Cagliari, Italy

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Cona, Italy

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Genova, Italy

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Milan, Italy

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Napoli, Italy

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Orbassano, Italy

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Palermo, Italy

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Pavia, Italy

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Pisa, Italy

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Reggio Calabria, Italy

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Roma, Italy

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Sassari, Italy

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Hazmiyeh, Lebanon

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Kota Bharu, Malaysia

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Kuala Lumpur, Malaysia

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Nijmegen, Netherlands

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Johannesburg, South Africa

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Parktown, South Africa

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Seoul, South Korea

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Barakaldo, Spain

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Barcelona, Spain

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Madrid, Spain

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Seville, Spain

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Valencia, Spain

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Geneva, Switzerland

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Zurich, Switzerland

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Taichung, Taiwan

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Taipei, Taiwan

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Bangkok, Thailand

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Chaingmai, Thailand

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Adana, Turkey (Türkiye)

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Ankara, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Izmir, Turkey (Türkiye)

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Leeds, United Kingdom

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Leicester, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Sheffield, United Kingdom

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Related Publications (6)

• Porter JB, El-Alfy M, Viprakasit V, Giraudier S, Chan LL, Lai Y, El-Ali A, Han J, Cappellini MD. Utility of labile plasma iron and transferrin saturation in addition to serum ferritin as iron overload markers in different underlying anemias before and after deferasirox treatment. Eur J Haematol. 2016 Jan;96(1):19-26. doi: 10.1111/ejh.12540. Epub 2015 Jun 23.

  PMID: 25691036 DERIVED

• Lee JW, Yoon SS, Shen ZX, Ganser A, Hsu HC, El-Ali A, Habr D, Martin N, Porter JB. Hematologic responses in patients with aplastic anemia treated with deferasirox: a post hoc analysis from the EPIC study. Haematologica. 2013 Jul;98(7):1045-8. doi: 10.3324/haematol.2012.077669. Epub 2013 Apr 12.

  PMID: 23585526 DERIVED

• Pennell DJ, Porter JB, Cappellini MD, Chan LL, El-Beshlawy A, Aydinok Y, Ibrahim H, Li CK, Viprakasit V, Elalfy MS, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A. Continued improvement in myocardial T2* over two years of deferasirox therapy in beta-thalassemia major patients with cardiac iron overload. Haematologica. 2011 Jan;96(1):48-54. doi: 10.3324/haematol.2010.031468. Epub 2010 Nov 11.

  PMID: 21071497 DERIVED

• Lee JW, Yoon SS, Shen ZX, Ganser A, Hsu HC, Habr D, Domokos G, Roubert B, Porter JB; EPIC study investigators. Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial. Blood. 2010 Oct 7;116(14):2448-54. doi: 10.1182/blood-2010-01-261289. Epub 2010 Jun 21.

  PMID: 20566896 DERIVED

• Pennell DJ, Porter JB, Cappellini MD, El-Beshlawy A, Chan LL, Aydinok Y, Elalfy MS, Sutcharitchan P, Li CK, Ibrahim H, Viprakasit V, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A. Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia. Blood. 2010 Mar 25;115(12):2364-71. doi: 10.1182/blood-2009-04-217455. Epub 2009 Dec 8.

  PMID: 19996412 DERIVED

• Cappellini MD, Porter J, El-Beshlawy A, Li CK, Seymour JF, Elalfy M, Gattermann N, Giraudier S, Lee JW, Chan LL, Lin KH, Rose C, Taher A, Thein SL, Viprakasit V, Habr D, Domokos G, Roubert B, Kattamis A; EPIC Study Investigators. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias. Haematologica. 2010 Apr;95(4):557-66. doi: 10.3324/haematol.2009.014696. Epub 2009 Nov 30.

  PMID: 19951979 DERIVED

MeSH Terms

Conditions

Thalassemia; Myelodysplastic Syndromes; Anemia, Diamond-Blackfan; Anemia

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bone Marrow Diseases; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Red-Cell Aplasia, Pure; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders

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

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 15, 2005
• Study Start: April 1, 2005
• Primary Completion: May 1, 2009
• Study Completion: July 1, 2010
• Last Updated: February 11, 2020

Record last verified: 2013-06

Locations

GB (5); IT (14); NL (1); DE (13); HK (1); IL (3); MY (2); TW (2); LE (1); KR (1); TU (4); ZA (2); BE (5); CH (2); EG (1); GR (4); FR (12); AU (7); CN (3); DK (4); ES (5); TH (2)