Iron Overload, Thalassemia
Conditions
Keywords
Thalassemia, Chelation, Iron Overload, Thalassemia patients with Iron overload
Brief summary
This is a pilot study looking at the safety and efficacy of giving combination chelation with deferasirox and deferoxamine. The hypothesis is that combination chelation is safe in decreasing overall iron in patients with thalassemia.
Detailed description
This was a phase two pilot clinical trial designed to evaluate the safety and efficacy of the combination of deferasirox and deferoxamine in transfusion dependent thalassemia with a range of systemic iron burden. The duration of combined therapy was 12 months. Changes in liver iron concentration, ferritin, myocardial iron, and serum creatinine was monitored.
Interventions
DRUGCombo Chelation with Deferasirox (Exjade) and Deferoxamine (DFO)
All subjects will be given Deferasirox 20-30 mg/kg for 7 days per week. All subject will be given Deferoxamine 50 mg/kg for 3-7 days per week. The number of days for Deferoxamine will be determined by liver iron concentration at baseline.
Sponsors
Elliott Vichinsky
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Transfusion Dependent Thalassemia * If iron between 5-15 mg/g dry liver by SQUID, subject must have a documented endocrinopathy or cardiac finding * Older than 8 years
Exclusion criteria
* Participating on another interventional clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Combined Treatment With Deferasirox and Deferoxamine Over 12 Months | 12 months | Change in liver iron concentration from baseline to 12 months with the use of combined chelation therapy. The change was calculated as the liver iron concentration at 12 months minus the value at baseline. |
| Change in Serum Creatinine During 12 Months Combined Chelation Therapy | 12 months | Comparison of average serum creatinine over 12 months of combined chelation therapy compared with baseline serum creatinine. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Deferasirox (Exjade) and Deferoxamine (DFO) Patients will receive combined chelation therapy using Deferasirox (Exjade) and Deferoxamine (DFO) with dosing based on liver iron concentration at baseline.
Patients with moderate iron overload,defined as liver iron concentration of 5-15mg/g plus a documented endocrinopathy or cardiac iron (low MRI T2\*), will receive 7 days per week of Deferasirox (Exjade) 20-30 mg/kg and Deferoxamine (DFO) 50 mg/kg 3-5 days per week.
Patients with high iron overload, defined as liver iron concentration over 15mg/g will receive Deferasirox (Exjade) 20-30 mg/kg 7 days per week and Deferoxamine (DFO) 50 mg/kg 5-7 days per week. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Deferasirox (Exjade) and Deferoxamine (DFO) |
|---|---|
| Age, Categorical Age, Categorical <=18 years | 6 Participants |
| Age, Categorical Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Age, Categorical Between 18 and 65 years | 16 Participants |
| Sex/Gender, Customized Sex/Gender Not Collected | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 22 |
| other Total, other adverse events | 1 / 22 |
| serious Total, serious adverse events | 2 / 22 |
Outcome results
Primary
Change in Serum Creatinine During 12 Months Combined Chelation Therapy
Comparison of average serum creatinine over 12 months of combined chelation therapy compared with baseline serum creatinine.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Deferasirox (Exjade) and Desferal (DFO) | Change in Serum Creatinine During 12 Months Combined Chelation Therapy | 0.09 mg/dl |
Primary
Efficacy of Combined Treatment With Deferasirox and Deferoxamine Over 12 Months
Change in liver iron concentration from baseline to 12 months with the use of combined chelation therapy. The change was calculated as the liver iron concentration at 12 months minus the value at baseline.
Time frame: 12 months
Population: Eighteen subjects completed one year of therapy. Four subjects did not complete the study for the following reasons: lost to follow-up (1), abdominal pain (1), death (1), and non-compliance (1).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deferasirox (Exjade) and Desferal (DFO) | Efficacy of Combined Treatment With Deferasirox and Deferoxamine Over 12 Months | -6.2 mg/g |