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

NCT01044186 | Completed Phase 2

• 2 other identifiers: CICL670A01172004-002303-32 EudraCT number
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 18

Brief Summary

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.

Conditions

Transfusional Iron Overload

Keywords

Deferasirox; ICL670A; Iron chelators; Deferiprone; Transfusional hemosiderosis; Congenital aplastic anemia (Diamond Blackfan anemia); Red cell aplasia; Thalassemia; β thalassemia

Outcome Measures

Primary Outcomes (1)

• 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.

  0 - 163 weeks

Secondary Outcomes (3)

• To estimate the absolute and relative change of liver iron concentration (LIC), to be measured using appropriate methodology available at individual centers.

  Yearly

• To evaluate the role of serum ferritin, serum iron, transferrin and transferrin saturation in monitoring iron burden in these patients.

  Quarterly

• To evaluate the relationship between changes in LIC and serum ferritin, transferring saturation and serum iron.

  Yearly

Study Arms (1)

ICL670

EXPERIMENTAL

Drug: ICL670

Interventions

ICL670 DRUG

ICL670

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

Children's Hospital and Research Center - Oakland

Oakland, California, 94609, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Queens Hospital Center

Jamaica, New York, 11432, United States

Location

New York Presbyterian Hospital/Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

New York Methodist Hospital

New York, New York, 11215, United States

Location

Cincinnatti Children's Hospital Medical center

Cincinnatti, Ohio, 45229, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis investigative Site

Athens, Greece

Location

Novartis Investigative Site

Ancona, Italy

Location

Novartis Investigative Site

Brindisi, Italy

Location

Novartis Investigative Site

Cagliari, Italy

Location

Novartis Investigative Site

Cosenza, Italy

Location

Novartis Investigative Site

Florence, Italy

Location

Novartis Investigative Site

Milan, Italy

Location

Novartis Investigative Site

Modena, Italy

Location

Novartis Investigative Site

Napoli, Italy

Location

Novartis Investigative Site

Torino, Italy

Location

Related Links

• Related Info

MeSH Terms

Conditions

Cystinosis; Anemia, Diamond-Blackfan; Red-Cell Aplasia, Pure; Thalassemia

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2010
• First Posted: January 7, 2010
• Study Start: June 1, 2003
• Primary Completion: December 1, 2007
• Last Updated: February 23, 2017

Record last verified: 2017-02

Locations

GR (1); IT (9); US (8)