Clinical trial NCT00171821: A Study Assessing the Efficacy and Safety of Deferasirox in Patients With Transfusion-dependent Iron Overload
Official title: A One Year, Open-label, Single-arm, Multi-center Trial Evaluating the Efficacy and Safety of Oral ICL670 (20 mg/kg/Day) in Patients Diagnosed With Transfusion-dependent Iron Overload
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Transfusion-dependent Iron Overload
Keywords: Thalassemia
Myelodysplastic Syndrome
MDS
Sickle cell
Diamond-Blackfan anemia
Transfusion
Anemia
Fanconi
Chelation
Deferasirox
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 1784
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Additional Inclusion Criteria for Adult Patients:

* Written informed consent by the patient

Additional Inclusion Criteria for Pediatric Patients:

* 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.

Exclusion Criteria:

* 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;
  * history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
  * history of pancreatic injury or pancreatitis; indications of impaired pancreatic function/injury as indicated by abnormal lipase or amylase;
  * history or presence of impaired renal function as indicated by creatinine or blood urea nitrogen (BUN) values equal or above ULN;
  * history of urinary obstruction or difficulty in voiding.
* History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
* History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the run-in period
* Patients with positive test to HIV
* Life expectancy of \< 1 year

Exclusion Criteria for Pediatric Patients:

* Patient body weight which prevents the use of the smallest tablet strength (i.e. 125 mg) for proper dosing

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: 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
timeFrame: at baseline and at 52 weeks
Secondary outcomes:
measure: To evaluate the safety and tolerability profile of in patients treated for up to 52 weeks
timeFrame: Monthly
measure: Evaluate efficacy, tolerabilty and safety in the subgroup of patients with baseline LIC < 7 mg Fe/g dw
timeFrame: Monthly
measure: Evaluate the relationship between serum ferritin and potential surrogate markers
timeFrame: Monthly
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Novartis Investigative Site
city: Camperdown
country: Australia
facility: Novartis Investigative Site
city: Clayton
country: Australia
facility: Novartis Investigative Site
city: Melbourne
country: Australia
facility: Novartis Investigative Site
city: Perth
country: Australia
facility: Novartis Investigative Site
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
city: Westmead
country: Australia
facility: Novartis Investigative Site
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Brussels
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Godinne
country: Belgium
facility: Novartis Investigative Site
city: La Louviere
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: GuangZhou
country: China
facility: Novartis Investigative Site
city: Nanjing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Arhus
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Herlev
country: Denmark
facility: Novartis Investigative Site
city: Hillerod
country: Denmark
facility: Novartis Investigative Site
city: Cairo
country: Egypt
facility: Novartis Investigative Site
city: Angers
country: France
facility: Novartis Investigative Site
city: Avignon
country: France
facility: Novartis Investigative Site
city: Bobigny
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Paris Cedex 14
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pessac Cedex
country: France
facility: Novartis Investigative Site
city: Rennes
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex
country: France
facility: Novartis Investigative Site
city: Vandoeuvre Les Nancy
country: France
facility: Novartis Investigative Site
city: Augsburg
country: Germany
facility: Novartis Investigative Site
city: Braunschweig
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Dusseldorf
country: Germany
facility: Novartis Investigative Site
city: Frankfurt/Main
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Frieburg
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Greifswald
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Larissa
country: Greece
facility: Novartis Investigative Site
city: Patras
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Afula
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Petach-Tikva
country: Israel
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
city: Brindisi
country: Italy
facility: Novartis Investigative Site
city: Cagliari
country: Italy
facility: Novartis Investigative Site
city: Cona
country: Italy
facility: Novartis Investigative Site
city: Genova
country: Italy
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Orbassano
country: Italy
facility: Novartis Investigative Site
city: Palermo
country: Italy
facility: Novartis Investigative Site
city: Pavia
country: Italy
facility: Novartis Investigative Site
city: Pisa
country: Italy
facility: Novartis Investigative Site
city: Reggio Calabria
country: Italy
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
city: Sassari
country: Italy
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Hazmiyeh
country: Lebanon
facility: Novartis Investigative Site
city: Kota Bahru
country: Malaysia
facility: Novartis Investigative Site
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Nijmegen
country: Netherlands
facility: Novartis Investigative Site
city: Johannesburg
country: South Africa
facility: Novartis Investigative Site
city: Parktown
country: South Africa
facility: Novartis Investigative Site
city: Baracaldo
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Geneve
country: Switzerland
facility: Novartis Investigative Site
city: Zurich
country: Switzerland
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chaingmai
country: Thailand
facility: Novartis Investigative Site
city: Adana
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.