Combination Deferasirox and Deferiprone for Severe Iron Overload in Thalassemia
Study Details
Study Description
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 |
---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Deferasirox and deferiprone
|
Drug: Deferasirox and deferiprone
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Improvement in Liver Iron Concentration [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 [12 months]
Improvement in Cardiac T2* MRI from baseline to determine if there is a reduction of cardiac iron burden.
Eligibility Criteria
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
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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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois | United States | 60611 |
2 | 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 12-009449
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Deferasirox and Deferiprone |
---|---|
Arm/Group Description | Deferasirox and deferiprone |
Period Title: Overall Study | |
STARTED | 9 |
COMPLETED | 6 |
NOT COMPLETED | 3 |
Baseline Characteristics
Arm/Group Title | Deferasirox and Deferiprone |
---|---|
Arm/Group Description | Deferasirox and deferiprone |
Overall Participants | 9 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
28.9
(5.6)
|
Sex: Female, Male (Count of Participants) | |
Female |
5
55.6%
|
Male |
4
44.4%
|
Region of Enrollment (Count of Participants) | |
United States |
9
100%
|
Outcome Measures
Title | Number of Participants With Improvement in Liver Iron Concentration |
---|---|
Description | 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 |
Time Frame | 12 months |
Outcome Measure Data
Analysis Population Description |
---|
Number with participants with improvement in liver iron concentration |
Arm/Group Title | Deferasirox and Deferiprone |
---|---|
Arm/Group Description | Deferasirox and deferiprone |
Measure Participants | 6 |
Count of Participants [Participants] |
3
33.3%
|
Title | Number of Participants With Improvement in Cardiac T2* MRI |
---|---|
Description | Improvement in Cardiac T2* MRI from baseline to determine if there is a reduction of cardiac iron burden. |
Time Frame | 12 months |
Outcome Measure Data
Analysis Population Description |
---|
Number of participants with improvement |
Arm/Group Title | Deferasirox and Deferiprone Combination Chelation |
---|---|
Arm/Group Description | Deferasirox and deferiprone |
Measure Participants | 6 |
Count of Participants [Participants] |
3
33.3%
|
Adverse Events
Time Frame | ||
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Deferasirox and Deferiprone | |
Arm/Group Description | Deferasirox and deferiprone | |
All Cause Mortality |
||
Deferasirox and Deferiprone | ||
Affected / at Risk (%) | # Events | |
Total | 0/9 (0%) | |
Serious Adverse Events |
||
Deferasirox and Deferiprone | ||
Affected / at Risk (%) | # Events | |
Total | 3/9 (33.3%) | |
Gastrointestinal disorders | ||
Rectal bleeding from hemorrhoid | 1/9 (11.1%) | 1 |
General disorders | ||
viral syndrome | 1/9 (11.1%) | 1 |
Infections and infestations | ||
perirectal abscess | 1/9 (11.1%) | 2 |
Other (Not Including Serious) Adverse Events |
||
Deferasirox and Deferiprone | ||
Affected / at Risk (%) | # Events | |
Total | 8/9 (88.9%) | |
Ear and labyrinth disorders | ||
Tinnitus | 1/9 (11.1%) | 1 |
Gastrointestinal disorders | ||
Diarrhea | 4/9 (44.4%) | 4 |
Nausea/vomiting | 3/9 (33.3%) | 3 |
Abdominal pain | 2/9 (22.2%) | 3 |
Hepatobiliary disorders | ||
ALT elevated | 1/9 (11.1%) | 1 |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 4/9 (44.4%) | 7 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Janet Kwiatkowski, MD |
---|---|
Organization | Children's Hospital of Philadelphia |
Phone | 215-590-3437 |
kwiatkowski@email.chop.edu |
- 12-009449