Safety, Tolerability, and Efficacy of Deferasirox in MDS

Study Overview
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Brief Summary
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Open label, single arm study on Deferasirox treatment in MDS patients with chronic transfusional hemosiderosis. Patients receive daily oral dosis of Deferasirox in order to eliminate the quantity of iron administered during transfusions and, if needed, to reduce the overload of already present iron. After an screening phase in which patients are evaluated according to eligibility criteria, a one year treatment phase foresees monthly visits to evaluate safety and efficacy signs.

Detailed Description
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It has been widely shown that an appropriate chelating therapy in chronic anemias transfusion dependent can prevent the overstock of iron and can reduce the already existing overstock reducing, then, the co-morbidity and improving survival. In particular, some authors have shown in MDS affected patients undergoing intensive chelating therapy with deferoxamine haematological recovery with a reduction of the need of transfusions. With the present study, we plan to evaluate the safety and efficacy of a therapy with the new oral chelating Deferasirox in MDS patients with transfusional hemosiderosis. This is an open label, single arm study on Deferasirox treatment in MDS patients with chronic transfusional hemosiderosis. Patients will receive daily oral dosis of Deferasirox in order to eliminate the quantity of iron administered during transfusions and, if needed, to reduce the overload of already present iron. After an screening phase in which patients are evaluated according to eligibility criteria, a one year treatment phase foresees monthly visits to evaluate safety and efficacy signs.

Official Title
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Open Label, Multicenter Study to Evaluate Safety/Tolerability and Efficacy of Deferasirox (ICL670) in Myelodysplastic Syndrome Patients With Chronic Transfusional Hemosiderosis.

Conditions
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Myelodysplastic Syndromes, Hemosiderosis

Intervention / Treatment
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* Drug: Deferasirox


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients, both males and females, with low and intermediate I risk (IPSS score) Myelodysplastic syndrome and transfusion-induced hemosiderosis. Age >=18 years Patients who never received chelation therapy or who received a therapy with Desferal after a day of wash out Medical history of at least 20 blood transfusions (equivalent to 100 ml/kg of red cells concentrate). Availability of data concerning blood transfusions during the 12 weeks before screening Serum ferritin >= 1000 µg/L at least twice (at least 2 week interval between the 2 analysis) during the year before the screening Life expectancy > 12 months Availability of at least 3 complete blood counts (before transfusions) during the 12 weeks before the screening Exclusion Criteria: Diagnosis different from MDS (i.e. myelofibrosis) Severe renal impairment (creatinine clearance < 60 ml/min) ALT/AST > 500 U/L Active B and/or C hepatitis Patients treated during the past 4 weeks with experimental drugs for MDS (including thalidomide, azacitidine, arsenic trioxide). These patients become eligible after a wash out of at least 4 weeks Concomitant treatment with another iron-chelating agent

Ages Eligible for Study
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Minimum Age: 18 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: Deferasirox<br> | Drug: Deferasirox<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the tolerability and safety profile of Deferasirox in pts with MDS with post-transfusional hemosiderosis |  | On a monthly basis thereafter from baseline assessment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate Deferasirox efficacy as chelation therapy in terms of reduction of serum ferritin levels compared to basal levels |  | At 3, 6, 9, and 12 months from baseline assessment. | 
| To evaluate the impact Deferasirox iron chelating therapy vs the normal demand of transfusions in a subgroup of pts that will not receive growth factors or chemotherapy according to their basal characteristics. |  | On a monthly basis thereafter from baseline assessment. | 
| Quality of Life evaluation. |  | At 3, 6, 9, and 12 months from baseline assessment. | 
| Compliance to chelating therapy evaluation. |  | On a monthly basis thereafter from baseline assessment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDS, Chronic transfusional hemosiderosis, Deferasirox