Extension Study of Iron Chelation Therapy With Deferasirox in β-thalassemia and Rare Chronic Anemia Patients

Extension Study of Iron Chelation Therapy With Deferasirox in β-thalassemia and Other Patients With Rare Chronic Anemia and Transfusional Iron Overload

A 1-year randomized Phase II core trial was conducted to investigate the efficacy of deferasirox in regularly transfused patients with β-thalassemia and other rare chronic anemia 2 years of age and older. Patients who successfully completed the main trial may continue in the extension trial to receive chelation therapy with deferasirox for up to 3 years. Extension was prolonged to 4 years.

The objective of this study is to assess the long-term safety and efficacy of deferasirox in these patient groups.

Study Overview

• Status: Completed
• Conditions: Anemia; Hemosiderosis
• Intervention / Treatment: Drug: Deferasirox

• Study Type: Interventional
• Enrollment (Actual): 184
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium
    • Novartis Investigative Site
  • Bruxelles, Belgium
    • Novartis Investigative Site
  • Gent, Belgium
    • Novartis Investigative Site
  • La Louvière, Belgium
    • Novartis Investigative Site
  • Leuven, Belgium
    • Novartis Investigative Site
• Canada
  • Montreal, Canada
    • Novartis Investigative Site
  • Toronto, Canada
    • Novartis Investigative Site
• France
  • Creteil, France
    • Novartis Investigative Site
  • Le Kremlin Bicetre, France
    • Novartis Investigative Site
  • Lille, France
    • Novartis Investigative Site
  • Troyes, France
    • Novartis Investigative Site
• Germany
  • Duesseldorf, Germany
    • Novartis Investigative Site
  • Hannover, Germany
    • Novartis Investigative Site
  • Ulm, Germany
    • Novartis Investigative Site
• Italy
  • Bologna, Italy
    • Novartis Investigative Site
  • Brindisi, Italy
    • Novartis Investigative Site
  • Cagliari, Italy
    • Novartis Investigative Site
  • Genova, Italy
    • Novartis Investigative Site
  • Milan, Italy
    • Novartis Investigative Site
  • Pavia, Italy
    • Novartis Investigative Site
  • Rome, Italy
    • Novartis Investigative Site
  • Torino, Italy
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom
    • Novartis Investigative Site
• United States
  • California
    • Oakland, California, United States, 94609-1809
      • Children's Hospital and Research Center at Oakland
    • Stanford, California, United States, 94305
      • Stanford Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Childres's Hospital Boston
  • New York
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4399
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients completed the planned 12-month core study
• Female patients who have reached menarche and who are sexually active must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation
• Written informed consent obtained from the patient and/or legal guardian on the patient's behalf in accordance with the national legislation

Exclusion Criteria:

• Pregnant or breast feeding patients

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deferasirox; Deferasirox daily oral dose between 5-40 mg/kg/day	Drug: Deferasirox; Deferasirox available as 125 mg, 250 mg or 500 mg tablets; Other Names: ICL670

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Deaths	Safety was assessed using reports of adverse events of all participants in this study. Serious adverse events are those events that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.	Core study Baseline to the end of the study (up to 60 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change in Liver Iron Content (LIC) as Assessed by Liver Biopsy at Baseline to the End of the Study	Liver iron concentration was monitored at the start of the core study, the end of the core study, and then at the end of the extension study. High-risk participants, like participants with rare anemia, were excluded from any further potential liver biopsy, except if required and justified by the Investigator for the general care of the participant.	Core study Baseline to end of extension study (up to 60 months)
The Absolute Change in Liver Iron Content (LIC) as Assessed by Superconducting Quantum Interference Device (SQUID) From Baseline to End of Study	Liver iron concentration was monitored at the end of the core study and then at the end of the extension study. High-risk participants, like participants with rare anemia, were excluded from any further potential liver biopsy, except if required and justified by the Investigator for the general care of the participant. Pediatric participants or participants with a medical contraindication to liver biopsy were allowed the use of SQUID in the extension study.	Core study Baseline to end of extension study (up to 60 months)
The Absolute Change in Serum Ferritin (μg/L) Levels From Baseline to the End of the Study	Serum ferritin was monitored monthly and the dose of deferasirox was increased or decreased in steps of 5 to 10 mg/kg/day up to a maximum of 40 mg/kg/day if appropriate, every 3 months. If serum ferritin fell to 500 ng/mL or lower on two consecutive study visits, an interruption of treatment until serum ferritin was more than 500 ng/mL was considered.	Core study Baseline to end of extension study (up to 60 months)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: October 14, 2005
• First Submitted That Met QC Criteria: March 15, 2006
• First Posted (Estimate): March 16, 2006

Study Record Updates

• Last Update Posted (Estimate): May 9, 2011
• Last Update Submitted That Met QC Criteria: April 15, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: iron overload; deferasirox; β-thalassemia; transfusional hemosiderosis; rare chronic anemia; chronic anemias
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Iron Metabolism Disorders; Metabolism, Inborn Errors; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Metal Metabolism, Inborn Errors; Iron Overload; Anemia; Thalassemia; beta-Thalassemia; Hemochromatosis; Hemosiderosis; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: CICL670A0108E1