Iron Overload After Hematopoietic Stem Cell Transplantation (HSCT) in Patients With Beta-thalassemia Major
Conditions
Keywords
hematopoietic stem cell transplantation, beta-thalassemia major, deferasirox, iron overload
Brief summary
This was a prospective, single-arm, multicenter, national, phase II clinical study. The purpose of this Phase II study was to examine the safety and efficacy of deferasirox to decrease iron overload (IOL) in the posttransplant period in patients with beta-thalassemia major.
Interventions
DRUGICL670
Oral dose of ICL670 at 10 mg/kg daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who had hematopoietic stem cell transplantation (HSCT) for beta-thalassemia major * hematopoietic stem cell transplantation (HSCT) was performed minimum 6 months and maximum 2 years ago * The washout period after the immunosuppressive therapy should be at least 3 months. * Signifacant IOL should be present including: A. Serum ferritin \>1000 μg/L or B. cardiac MRI \<20 ms or C. liver iron concentration ≥ 5 mg/g dry weight measured by R2\* MRI
Exclusion criteria
* Patients who had any contraindication for treatment with deferasirox according to the prescribing information •Patients who depended on transfusion * Patients with clinical symptoms of cardiac dysfunction (shortness of breath at rest or exertion, orthopnea, exercise intolerance, lower extremity edema, arrhythmias) * Patients who were experiencing severe complication of HSCT e.g. acute Graft-versus host disease (GVHD) * Significant proteinuria / Increase in serum creatinine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events, Serious Adverse Events and Deaths as a Measure of Safety and Tolerability | 12 months | To determine the safety; incidence, type and severity of adverse events including renal, hepatic, biochemistry and hematologic parameters of deferasirox in the treatment of iron overload after hematopoietic stem cell transplantation (HSCT) in patients with beta-thalassemia major in 12 months period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Ferritin Level. | Baseline, 12 Months | Blood samples were collected and serum levels were assessed at study baseline (BL) and at 12 months. |
| Change in the Further Parameters of Iron Overload (Liver Iron Concentration by Magnetic Resonance Imaging (MRI Examination) | Baseline, 12 month | Liver Iron Concentration (LIC) values between 3 and 7 mg Fe / g dry weight are indicative of mild iron deposition, while values between 7 and 15 mg Fe / g dry weight are indicative of moderate iron deposition which have been associated with liver disease. Values \>15 mg Fe/g dry weight are indicative of severe iron deposition which is associated with progressive liver fibrosis, increased morbidity and mortality |
| The Percentage of Patients Reaching Serum Ferritin Levels Lower Than 500 μg/L | Week 28 and Week 52 | Serum Ferritin values between 1000-2500 μg/L are indicative of mild to moderate iron overload while values \>2500 μg/L are indicative of severe iron overload and levels constantly higher than 2500 μg/L has been shown to to increase the risk of cardiac complications and endocrine disease. Maintaining levels \<1000 μg/L is associated with increased survival and less morbidity. |
| Change in the Further Parameters of Iron Overload (Cardiac Iron Concentration by Magnetic Resonance Imaging (MRI Examination) | Baseline, 12 month | Cardiac MRI values between 10 to 20 milliseconds (ms) are indicative of moderate cardiac iron deposition associated with declining left ventricular ejection fraction and arrhythmias while values \<10 ms are indicative of deposition sufficient to risk cardiac decompensation and associated with overt heart failure and mortality. |
Countries
Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ICL670 Oral dose of ICL670 at 10 mg/kg daily | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | ICL670 |
|---|---|
| Age, Continuous | 9.07 years STANDARD_DEVIATION 3.81 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 27 |
| serious Total, serious adverse events | 3 / 27 |
Outcome results
Primary
Number of Participants With Adverse Events, Serious Adverse Events and Deaths as a Measure of Safety and Tolerability
To determine the safety; incidence, type and severity of adverse events including renal, hepatic, biochemistry and hematologic parameters of deferasirox in the treatment of iron overload after hematopoietic stem cell transplantation (HSCT) in patients with beta-thalassemia major in 12 months period
Time frame: 12 months
Population: The Safety Set (SS) includes all included patients who were included in the study. All statistical analyses of safety and tolerability will be done in the SS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ICL670 | Number of Participants With Adverse Events, Serious Adverse Events and Deaths as a Measure of Safety and Tolerability | Adverse events | 25 Participants |
| ICL670 | Number of Participants With Adverse Events, Serious Adverse Events and Deaths as a Measure of Safety and Tolerability | Serious adverse events | 3 Participants |
| ICL670 | Number of Participants With Adverse Events, Serious Adverse Events and Deaths as a Measure of Safety and Tolerability | Death | 0 Participants |
Secondary
Change in Serum Ferritin Level.
Blood samples were collected and serum levels were assessed at study baseline (BL) and at 12 months.
Time frame: Baseline, 12 Months
Population: The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ICL670 | Change in Serum Ferritin Level. | Baseline | 1766.81 ng/mL | Standard Deviation 599.64 |
| ICL670 | Change in Serum Ferritin Level. | Month 12 | 903.56 ng/mL | Standard Deviation 596.62 |
Secondary
Change in the Further Parameters of Iron Overload (Cardiac Iron Concentration by Magnetic Resonance Imaging (MRI Examination)
Cardiac MRI values between 10 to 20 milliseconds (ms) are indicative of moderate cardiac iron deposition associated with declining left ventricular ejection fraction and arrhythmias while values \<10 ms are indicative of deposition sufficient to risk cardiac decompensation and associated with overt heart failure and mortality.
Time frame: Baseline, 12 month
Population: The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ICL670 | Change in the Further Parameters of Iron Overload (Cardiac Iron Concentration by Magnetic Resonance Imaging (MRI Examination) | Baseline Cardiac MRI(n= 27) | 26.48 ms | Standard Deviation 7.49 |
| ICL670 | Change in the Further Parameters of Iron Overload (Cardiac Iron Concentration by Magnetic Resonance Imaging (MRI Examination) | Week 52 Cardiac MRI (n=24) | 28.25 ms | Standard Deviation 5.53 |
Secondary
Change in the Further Parameters of Iron Overload (Liver Iron Concentration by Magnetic Resonance Imaging (MRI Examination)
Liver Iron Concentration (LIC) values between 3 and 7 mg Fe / g dry weight are indicative of mild iron deposition, while values between 7 and 15 mg Fe / g dry weight are indicative of moderate iron deposition which have been associated with liver disease. Values \>15 mg Fe/g dry weight are indicative of severe iron deposition which is associated with progressive liver fibrosis, increased morbidity and mortality
Time frame: Baseline, 12 month
Population: The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ICL670 | Change in the Further Parameters of Iron Overload (Liver Iron Concentration by Magnetic Resonance Imaging (MRI Examination) | Baseline Liver MRI(n= 27) | 12.07 mg Fe/g dry liver weight | Standard Deviation 9.42 |
| ICL670 | Change in the Further Parameters of Iron Overload (Liver Iron Concentration by Magnetic Resonance Imaging (MRI Examination) | Week 52 Liver MRI (n=25) | 4.62 mg Fe/g dry liver weight | Standard Deviation 2.85 |
Secondary
The Percentage of Patients Reaching Serum Ferritin Levels Lower Than 500 μg/L
Serum Ferritin values between 1000-2500 μg/L are indicative of mild to moderate iron overload while values \>2500 μg/L are indicative of severe iron overload and levels constantly higher than 2500 μg/L has been shown to to increase the risk of cardiac complications and endocrine disease. Maintaining levels \<1000 μg/L is associated with increased survival and less morbidity.
Time frame: Week 28 and Week 52
Population: The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ICL670 | The Percentage of Patients Reaching Serum Ferritin Levels Lower Than 500 μg/L | Week 28 (n=26) | 7.7 Percentage of Patients |
| ICL670 | The Percentage of Patients Reaching Serum Ferritin Levels Lower Than 500 μg/L | Week 52 (n=27) | 33.3 Percentage of Patients |