Thalassemia Major With Severe Transfusional Iron Overload
Conditions
Keywords
Thalassemia, Chelation, Transfusion, Safety
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.
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.
Interventions
DRUGDeferasirox and deferiprone
Sponsors
The Cooley's Anemia Foundation,
Ann & Robert H Lurie Children's Hospital of Chicago
Children's Hospital of Philadelphia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Deferasirox and Deferiprone Deferasirox and deferiprone | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Deferasirox and Deferiprone |
|---|---|
| Age, Continuous | 28.9 years STANDARD_DEVIATION 5.6 |
| Region of Enrollment United States | 9 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 8 / 9 |
| serious Total, serious adverse events | 3 / 9 |
Outcome results
Primary
Number of Participants With Improvement in Liver Iron Concentration
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
Population: Number with participants with improvement in liver iron concentration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Deferasirox and Deferiprone | Number of Participants With Improvement in Liver Iron Concentration | 3 Participants |
Secondary
Number of Participants With Improvement in Cardiac T2* MRI
Improvement in Cardiac T2\* MRI from baseline to determine if there is a reduction of cardiac iron burden.
Time frame: 12 months
Population: Number of participants with improvement
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Deferasirox and Deferiprone | Number of Participants With Improvement in Cardiac T2* MRI | 3 Participants |