Post Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II, Multi-center, Single-arm, Prospective Study to Evaluate the Safety and Efficacy of Deferasirox in Beta-thalassemia Major Patients After Hematopoietic Stem Cell Transplantation.

Conditions
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Iron Overload After Hematopoietic Stem Cell Transplantation (HSCT) in Patients With Beta-thalassemia Major

Intervention / Treatment
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* Drug: ICL670


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ICL670<br>Oral dose of ICL670 at 10 mg/kg daily | Drug: ICL670<br>* Oral dose of ICL670 at 10 mg/kg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Ferritin Level. | Blood samples were collected and serum levels were assessed at study baseline (BL) and at 12 months. | Baseline, 12 Months | 
| 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 | Baseline, 12 month | 
| 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. | Week 28 and Week 52 | 
| 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. | Baseline, 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hematopoietic stem cell transplantation, beta-thalassemia major, deferasirox, iron overload