A Protocol to Allow Treatment With ICL670 for Patients With or at Risk of Life-threatening Complications of Transfusional Iron Overload Who Are Unable to Tolerate Other Iron Chelators Because of Documented Severe Toxicity

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01044186
First received: January 5, 2010
Last updated: November 26, 2012
Last verified: November 2012
  Purpose

The purpose of this open-label, non-comparative, multi-center protocol was to further evaluate safety and to provide treatment with ICL670 to patients who had or were at risk of life threatening complications due to transfusional iron overload with a documented inability to tolerate any of the commercially available iron chelators due to severe toxicity rendering continued therapy either impossible or hazardous. Patients who were also ineligible for all on-going registration trials with ICL670 were included in the study. In exceptional cases, patients with a degree of iron overload which was not immediately life-threatening and who were ineligible for the registration trials were also enrolled provided they had a well-documented, sound justification for alternative chelation therapy.


Condition Intervention Phase
Transfusional Iron Overload
Drug: ICL670
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Protocol to Allow Treatment With ICL670 for Patients With or at Risk of Life-threatening Complications of Transfusional Iron Overload Who Are Unable to Tolerate Other Iron Chelators Because of Documented Severe Toxicity

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • To evaluate the safety profile and to provide treatment with ICL670 for patients with or at risk of life-threatening complications due to transfusional iron overload who are unable to tolerate other iron chelators because of documented severe toxicity. [ Time Frame: 0 - 163 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To estimate the absolute and relative change of liver iron concentration (LIC), to be measured using appropriate methodology available at individual centers. [ Time Frame: Yearly ] [ Designated as safety issue: No ]
  • To evaluate the role of serum ferritin, serum iron, transferrin and transferrin saturation in monitoring iron burden in these patients. [ Time Frame: Quarterly ] [ Designated as safety issue: No ]
  • To evaluate the relationship between changes in LIC and serum ferritin, transferring saturation and serum iron. [ Time Frame: Yearly ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: June 2003
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ICL670 Drug: ICL670

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients had to be at risk of life-threatening complications due to transfusional iron overload and be unable to tolerate therapy with any of the commercially available iron chelators (mainly deferoxamine and/or deferiprone) because of documented severe toxicity.
  • Patients with a degree of iron overload which was not immediately life-threatening and who were ineligible for other trials with ICL670 could also be enrolled providing they had a well-documented, sound justification for alternative chelation therapy.
  • Serum ferritin ≥ 8000 μg/L.
  • Serum ferritin < 8000μg/L and LIC of ≥ 7 mg Fe/g dry weight.
  • Patients for whom ≥ 8 blood transfusions per year were required in order to maintain the Hemoglobin level at > 9 g/dL.
  • Female patients who have reached menarche and who were sexually active had to use double barrier contraception (oral plus barrier contraception), or had to have undergone total hysterectomy and/or ovariectomy, or tubal ligation.
  • Written, voluntary informed consent.

Exclusion Criteria:

  • Patients with transfusional iron overload who were not experiencing severe toxicities during therapy with other iron chelators (e.g. deferoxamine and/or deferiprone).
  • Patients with non-transfusional hemosiderosis.
  • Patients with severe liver failure as defined by a score of ≥ 10 points on the Child-Pugh scale.
  • Patients with serum creatinine 1.5 times the upper limit of normal (ULN) at screening.
  • Patients with a history of nephrotic syndrome.
  • Patients with a diagnosis of clinically relevant cataract or a previous history of clinically relevant ocular toxicity related to iron chelation therapy.
  • Patients with severe systemic diseases unrelated to iron overload and which would prevent them from undergoing treatment with ICL670.
  • Patients with psychiatric or addictive disorders which prevent them from giving informed consent or undergoing treatment with ICL670.
  • Pregnant or breast feeding patients.
  • Patients treated with systemic investigational drugs within the past four weeks or topical investigational drugs within the past seven days.
  • Any surgical or medical condition which might significantly alter the absorption or excretion of drugs as shown by evidence of any of the following:

    • History of inflammatory bowel disease
    • History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
    • History of pancreatic injury or pancreatitis; indication of impaired pancreatic function/injury as indicated by abnormal lipase or amylase
  • Patients being considered by the investigator as potentially unreliable and/or not cooperative with regard to the protocol.
  • History of drug or alcohol abuse within the 12 months prior to dosing.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01044186

Locations
United States, California
Children's Hospital and Research Center - Oakland
Oakland, California, United States, 94609
Children's Hospital of Orange County
Orange, California, United States, 92868
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, New York
Queens Hospital Center
Jamaica, New York, United States, 11432
New York Presbyterian Hospital/Weill Medical College of Cornell University
New York, New York, United States, 10021
New York Methodist Hospital
New York, New York, United States, 11215
United States, Ohio
Cincinnatti Children's Hospital Medical center
Cincinnatti, Ohio, United States, 45229
United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77030
Greece
Novartis investigative Site
Athens, Greece
Italy
Novartis Investigative Site
Ancona, Italy
Novartis Investigative Site
Brindisi, Italy
Novartis Investigative Site
Cagliari, Italy
Novartis Investigative Site
Cosenza, Italy
Novartis Investigative Site
Firenze, Italy
Novartis Investigative Site
Milano, Italy
Novartis Investigative Site
Modena, Italy
Novartis Investigative Site
Napoli, Italy
Novartis Investigative Site
Torino, Italy
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01044186     History of Changes
Other Study ID Numbers: CICL670A0117, 2004-002303-32 EudraCT number
Study First Received: January 5, 2010
Last Updated: November 26, 2012
Health Authority: United States: Food and Drug Administration
Italy: Ministry of Health
Greece: Ministry of Health and Welfare

Keywords provided by Novartis:
Deferasirox
ICL670A
Iron chelators
Deferiprone
Transfusional hemosiderosis
Congenital aplastic anemia (Diamond Blackfan anemia)
Red cell aplasia
Thalassemia
β thalassemia

Additional relevant MeSH terms:
Iron Overload
Iron Metabolism Disorders
Metabolic Diseases
Chelating Agents
Deferasirox
Iron
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Iron Chelating Agents

ClinicalTrials.gov processed this record on April 14, 2014