Combination Deferasirox and Deferiprone for Severe Iron Overload in Thalassemia
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| ClinicalTrials.gov Identifier: NCT01709032 |
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Recruitment Status :
Completed
First Posted : October 17, 2012
Results First Posted : March 6, 2019
Last Update Posted : March 6, 2019
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Sponsor:
Children's Hospital of Philadelphia
Collaborators:
The Cooley's Anemia Foundation,
Ann & Robert H Lurie Children's Hospital of Chicago
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
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Brief Summary:
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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Thalassemia Major With Severe Transfusional Iron Overload | Drug: Deferasirox and deferiprone | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 9 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (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 |
| Actual Study Start Date : | September 2012 |
| Actual Primary Completion Date : | August 1, 2015 |
| Actual Study Completion Date : | August 1, 2017 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Beta thalassemia
| Arm | Intervention/treatment |
|---|---|
| Experimental: Deferasirox and deferiprone |
Drug: Deferasirox and deferiprone
Other Names:
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Primary Outcome Measures :
- Number of Participants With Improvement in Liver Iron Concentration [ Time Frame: 12 months ]Determine the safety of the combination of Deferasirox and Deferiprone for the treatment of subjects with Thalassemia Major and Severe Iron Overload by assessing change in liver iron concentration from baseline to follow-up
Secondary Outcome Measures :
- Number of Participants With Improvement in Cardiac T2* MRI [ Time Frame: 12 months ]Improvement in Cardiac T2* MRI from baseline to determine if there is a reduction of cardiac iron burden.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| 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). Subjects who refuse to use deferoxamine after extensive consultation with at least 2 health care providers will also be allowed to participate.
- Pregnant or breastfeeding females
- Unwilling or unable to comply with study related procedures
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01709032
Locations
| United States, Illinois | |
| Ann & Robert H. Lurie Children's Hospital of Chicago | |
| Chicago, Illinois, United States, 60611 | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | |
| Philadelphia, Pennsylvania, United States, 19104 | |
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 |
| Responsible Party: | Children's Hospital of Philadelphia |
| ClinicalTrials.gov Identifier: | NCT01709032 |
| Other Study ID Numbers: |
12-009449 |
| First Posted: | October 17, 2012 Key Record Dates |
| Results First Posted: | March 6, 2019 |
| Last Update Posted: | March 6, 2019 |
| Last Verified: | February 2019 |
Keywords provided by Children's Hospital of Philadelphia:
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Thalassemia Chelation Transfusion Safety |
Additional relevant MeSH terms:
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Thalassemia beta-Thalassemia Iron Overload Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn |
Iron Metabolism Disorders Metabolic Diseases Deferasirox Deferiprone Iron Chelating Agents Chelating Agents Sequestering Agents Molecular Mechanisms of Pharmacological Action |