Expanded Access of Deferasirox to Patients With Congenital Disorders of Red Blood Cells and Chronic Iron Overload

Study Overview
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Brief Summary
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This is an open-label, non-randomized, multi-center trial designed to provide expanded access of deferasirox to patients with congenital disorders of red blood cells and chronic iron overload from blood transfusions who cannot adequately be treated with locally approved iron chelators.

Official Title
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A Study to Provide Expanded Access of (Exjade®) Deferasirox to Patients With Congenital Disorders of Red Blood Cells and Chronic Iron Overload From Blood Transfusions Who Cannot Adequately be Treated With Other Locally Approved Iron Chelators

Conditions
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Thalassemia, Sickle Cell Disease, Diamond Blackfan Anemia, Myelofibrosis

Intervention / Treatment
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* Drug: Deferasirox


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients greater than or equal to 2 years of age Documented congenital disorder of red blood cells (e.g., β-thalassemia major, sickle cell anemia, diamond-blackfan anemia) requiring ongoing blood transfusions Cannot be adequately treated with a locally approved iron chelator due to one of the following reasons: Documented non-compliance, defined as having taken less than 50% of the prescribed chelation therapy doses in the 12 months prior to study entry Contraindications, unacceptable toxicities and/or documented poor response to locally approved iron chelators despite proper compliance History of at least 20 blood transfusions (equivalent to 100 mL/kg of packed red blood cells (PRBC]) Serum ferritin value greater than or equal to 1000 µg/L Ability to comply with all study-related procedures, medications, and evaluations Exclusion Criteria: Ongoing treatment with another iron chelator (Any other iron chelation therapy must be discontinued at least 24 hours prior to study entry.) Patients who meet the eligibility criteria for any other ongoing Novartis sponsored clinical study protocol with deferasirox and who have geographic access to these sites Patients unable to tolerate (or who have unacceptable toxicities to) prior treatment with deferasirox Serum creatinine above the upper limit of normal at screening. Patients with ALT ≥ 500 U/L at screening. Evidence of chelation-related cataracts or hearing loss within 4 weeks prior to baseline Pregnancy (as indicated by serum β-HCG pregnancy test at screening for all female patients with the potential to become pregnant) and patients who are breastfeeding Patients treated with systemic investigational drug within 4 weeks prior to or with topical investigational drug within 7 days prior to the baseline visit Other protocol-defined inclusion/exclusion criteria may apply.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deferasirox<br>Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Starting dose was determined by the frequency of blood transfusions and recommended initial daily dose of deferasirox is 20 mg/kg body weight for patients receiving blood transfusion, 10 mg/kg for patients receiving less frequent transfusion/exchange transfusion and 30 mg/kg for patients receiving more frequent blood transfusions. | Drug: Deferasirox<br>* 125 mg, 250 mg and 500 mg tablets. Dosage was calculated based on participant's body weight. Tablets were dispersed in water, orange or apple juice and taken orally once a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Profile of Deferasirox Based Upon Drug Administration and Reporting of Serious Adverse Events | Safety as assessed by the number of participants with death, serious adverse events (SAE), and/or Adverse Events (AEs) leading to study drug interruption or discontinuation. Note: only treatment emergent AEs are summarized. | Baseline to end of study (Median exposure time to drug was approximately 30 weeks; Maximum exposure was 104 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in Serum Ferritin Values From Baseline Through Completion of the Study | The number of participants with Improvement, No Change or Worsening in Serum ferritin category levels at the end of the study compared to baseline. Serum ferritin levels in µg/L were divided into to 6 categories: (<1000), (1000-<2500), (2500-<4000), (4000-<5500), (5500-<7000) and (>=7000). Improvement was defined as a shift to a lower category at the end of study compared to the category at baseline. Worsening was defined as a shift to a higher category at the end of the study compared to the category at baseline. No change was no change in category at end of study from baseline. | Baseline to end of study (Median exposure time to drug was approximately 30 weeks; Maximum exposure was 104 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deferasirox, Congenital Anemias, Anemias, Red Blood Cell Disorders, Chronic Iron Overload, Transfusional Iron Overload, Iron Chelators, Oral Iron Chelators, Thalassemia, Sickle Cell Disease, Diamond Blackfan Anemia, Myelofibrosis, ICL670A