Study of Deferasirox for Treatment of Transfusional Iron Overload in Myelodysplastic Patients

• Changes in serum ferritin from baseline to 3, 6, 9 and 12 months after initiating treatment [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]
• Effect of non-transferrin bound iron (NTBI), serum iron, transferrin and transferrin saturation on the safe administration of deferasirox [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]
• Changes in transfusion requirements, serum erythropoietin levels, and estimated frequency of hematologic improvement in patients who are not receiving growth factors or chemotherapy for their underlying MDS. [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]
• Trough pharmacokinetic parameters of deferasirox in patients with MDS [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
• Drug accountability [ Time Frame: through out the study ] [ Designated as safety issue: No ]

• Efficacy of deferasirox based on changes in serum ferritin
• To evaluate the role of NTBI (LPI and DCI), serum iron, transferrin and transferrin saturation
• To evaluate change in transfusion requirements
• To evaluate trough pharmacokinetics
• To assess drug accountability
• To explore the utility of magnetic resonance imaging (MRI)

The purpose of this trial is to examine the safety and efficacy of deferasirox in patients with Myelodysplastic Syndrome (MDS) and chronic iron overload from blood transfusions.

Study entry requires a diagnosis of low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria and serum ferritin ≥ 1000 ng/mL. Patients must have had at least 30 prior red blood cell transfusions. Deferasirox will be administered at an initial dose of 20 mg/kg orally once per day. Patient transfusion history and at least three complete blood count (CBC) values must be available for the 12 weeks prior to study registration for patients with MDS and chronic iron overload from blood transfusions.

• Myelodysplastic Syndrome
• Iron Overload

Inclusion Criteria:

• Male or female patients with low or intermediate (INT-1) risk MDS
• Patients can be EITHER naïve to iron chelation OR have had prior treatment with deferoxamine (DFO).
• Age greater than or equal to 18 years
• Availability of transfusion records for the 12 weeks prior to registration
• A lifetime minimum of 30 previous packed red blood cell transfusions
• Availability of at least three CBC values (pretransfusion) during the 12 weeks prior to registration
• Serum Ferritin:

For entry into the screening period, serum ferritin ≥ 1000 ng/mL on at least two occasions, at least two weeks apart, during the prior year.

Serum ferritin ≥ 1000 ng/mL at screening via the central lab.

• Life expectancy ≥ 6 months
• Sexually active women must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined as amenorrhea for at least 12 months)
• Able to provide written informed consent

Exclusion Criteria:

• Serum creatinine above the upper limit of normal
• ALT > 500 U/L during screening
• Clinical or laboratory evidence of active Hepatitis B or C
• Urinary protein/creatinine ratio > 0.5 mg/mg
• History of HIV positive test result (ELISA or Western blot)
• ECOG Performance Status > 2
• Patients with uncontrolled systemic hypertension
• Unstable cardiac disease not controlled by standard medical therapy
• Patients with a diagnosis of or history of clinically relevant ocular toxicity related to iron chelation
• Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment
• Pregnancy or breast feeding
• Treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days
• Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug
• History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative