Combination Deferasirox and Deferiprone for Severe Iron Overload in Thalassemia
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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 |
- 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
- 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: Treatment with combination deferasirox and deferiprone |
Drug: Deferasirox and deferiprone
Other Names:
|
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 |
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 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| Contact: Vanessa Nixon, RN | 215-590-2197 |
| 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 | |
| Canada, Ontario | |
| Toronto General Hospital/University Health Network | Not yet recruiting |
| Toronto, Ontario, Canada | |
| Contact: Richard Ward 416-340-5233 | |
| Principal Investigator: Richard Ward, MRCP, FRCPath | |
| 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: | October 17, 2012 |
| 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 Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 17, 2013