Combination Deferasirox and Deferiprone for Severe Iron Overload in Thalassemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Children's Hospital of Philadelphia
Sponsor:
Collaborators:
The Cooley’s Anemia Foundation,
Ann & Robert H Lurie Children's Hospital of Chicago
Information provided by (Responsible Party):
Janet Kwiatkowski, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01709032
First received: October 16, 2012
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

We hypothesize that the combination treatment with deferasirox and deferiprone will be well tolerated and will result in significant improvement in cardiac and liver iron levels.


Condition Intervention Phase
Thalassemia Major With Severe Transfusional Iron Overload
Drug: Deferasirox and deferiprone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Deferasirox and Deferiprone Combination Oral Chelation for Individuals With Transfusion Dependent Thalassemia and High Iron Burden

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • Determine the safety of the combination of deferasirox and deferiprone for the treatment of subjects with thalassemia major and severe iron overload [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Safety and tolerability of the two oral chelators in combination based on clinical assessments (ex. incidence and severity of adverse events), physical examinations, and clinical laboratory values


Secondary Outcome Measures:
  • To obtain preliminary efficacy data on the reduction in serum ferritin level and liver iron concentration by R2 magnetic resonance imaging (MRI) and improvement in cardiac T2* MRI (estimation of cardiac iron loading) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: September 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Deferasirox and deferiprone Drug: Deferasirox and deferiprone
Other Names:
  • Exjade
  • Ferriprox

Detailed Description:

Death and disability from iron related damage to the heart remain the most serious issue facing transfusion-dependent patients with thalassemia. However, over the past decade there have been several reports of improved survival and fewer cardiac complications. This improvement may be related to the availability of three chelators and also the accurate measurement of iron stores in various organs (e.g. heart and liver) with magnetic resonance imaging, which allows for personalized, tailored medical care for patients. The chelator characteristics, side effect profiles, and ability to remove iron from specific organs differ among the chelators, suggesting that combination therapy may be beneficial. Using two drugs at lower doses may be more tolerable than escalating doses of a single drug and may improve iron removal. The combination of deferoxamine and deferiprone has been shown to be particularly beneficial for reducing cardiac iron, but it requires a painful injection/infusion, which hinders adherence. This pilot study aims to investigate the safety of an oral-only combination chelator regimen (deferasirox and deferiprone) in individuals with thalassemia major with poorly controlled iron overload and to assess how well this chelator combination lowers iron stores over one year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Alpha or beta thalassemia
  • Receiving chronic transfusions (at least 20 transfusions in lifetime) with iron overload requiring treatment with chelation
  • Serum ferritin >500 ng/ml
  • Liver iron concentration equal to or greater than 10 mg/g dw (by R2 MRI) or 7 to 10 mg/g dw (by R2 MRI) and not improving OR cardiac T2* between 6 and <20 ms
  • Women of childbearing age must have a negative pregnancy test
  • Agree to use approved method of contraception for the duration of the study
  • Subjects must have a good understanding of the study and be willing to comply with study procedures

Exclusion Criteria:

  • Subjects with past history of unexplained neutropenia (ANC < 1500/mcL), clinically significant renal disease (creatinine above the upper limit of normal), proteinuria >300 mg/L, clinically significant liver disease (ALT > 5x upper limit of normal), pulmonary or cardiovascular disease
  • History of other clinically relevant oral, endocrine, neurologic, psychiatric, immunologic, bone marrow or skin disorder that contraindicates dosing with deferasirox or deferiprone
  • History of adverse reaction or known allergy to either deferasirox or deferiprone necessitating drug discontinuation
  • Currently receiving treatment for active hepatitis
  • Use of any investigational agent in the past 30 days
  • Cardiac T2* <6 ms, left ventricular ejection fraction < 56%, and/or arrhythmia (certain subjects may be eligible if they have already had a trial of deferoxamine and deferiprone)
  • Pregnant or breastfeeding females
  • Unwilling or unable to comply with study related procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01709032

Contacts
Contact: Vanessa Nixon, RN 215-590-2197

Locations
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States
Contact: Alexis Thompson, MD         
Principal Investigator: Alexis A Thompson, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Vanessa Nixon, RN    215-590-2197      
Principal Investigator: Janet L Kwiatkowski, MD, MSCE         
Sponsors and Collaborators
Children's Hospital of Philadelphia
The Cooley’s Anemia Foundation,
Ann & Robert H Lurie Children's Hospital of Chicago
Investigators
Principal Investigator: Janet L Kwiatkowski, MD, MSCE Children's Hospital of Philadlephia
  More Information

No publications provided

Responsible Party: Janet Kwiatkowski, Associate Professor of Pediatrics, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01709032     History of Changes
Other Study ID Numbers: 12-009449
Study First Received: October 16, 2012
Last Updated: June 18, 2013
Health Authority: United States: Institutional Review Board
United States: Project Safety Officer
Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by Children's Hospital of Philadelphia:
Thalassemia
Chelation
Transfusion
Safety

Additional relevant MeSH terms:
Beta-Thalassemia
Thalassemia
Iron Overload
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Iron Metabolism Disorders
Metabolic Diseases
Deferiprone
Deferasirox
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014