Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients

Inclusion Criteria:

• Male or female patients with low or intermediate (INT-1) risk MDS, determined via IPSS criteria, with transfusional iron overload. NOTE: Bone marrow morphology and cytogenetic studies completed within 3 months prior to screening can be used if the patient has been hematologically stable. Every attempt to obtain cytogenetics studies should be made; however, if there is culture failure, repeat marrow aspiration will not be mandated. In this case, RAEB with less than 11% marrow blasts will be accepted.
• Patients can be EITHER naïve to iron chelation OR have had prior treatment with deferoxamine (DFO). DFO must be discontinued the day prior to starting deferasirox dosing.
• Age: greater than or equal to 18 years

• Serum ferritin:

  • For entry into the screening period: serum ferritin greater than or equal to 1000 µg/mL on at least two occasions, at least two weeks apart, during the prior year. Samples must be obtained in the absence of concomitant infection;
  • For enrollment into the study: serum ferritin greater than or equal to 1000 µg/mL at screening (via the central lab) obtained in the absence of concomitant infection
• A lifetime minimum of 30 previous packed red cell transfusions
• Life expectancy greater than or equal to 6 months
• Women must have a negative serum or urine pregnancy test and use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined by amenorrhea for at least 12 months).
• Able to provide written informed consent

Exclusion Criteria:

• Serum creatinine above the upper limit of normal
• ALT greater than 250 U/L during screening
• Clinical or laboratory evidence of active hepatitis B or hepatitis C (HBsAg in the absence of HBsAb -OR- HCV Ab positive with HCV RNA positive and ALT above the normal range)
• Significant proteinuria as indicated by a urinary protein/creatinine ratio greater than 0.5 mg/mg in a non-first void urine sample during screening (or alternatively in two of three samples obtained for screening)
• History of HIV positive test result (ELISA or Western blot)
• ECOG performance status greater than 2
• Uncontrolled systemic hypertension
• Unstable cardiac disease not controlled by standard medical therapy
• Third degree atrioventricular (AV) block or QT interval prolongation above the normal range
• 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 a systemic investigational drug within the past 4 weeks or a topical investigational drug within the past 7 days.

• Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following:

  • inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;
  • major gastrointestinal tract surgery, such as gastrectomy, gastroenterostomy, or bowel resection;
  • pancreatic injury or pancreatitis or indications of impaired pancreatic function/injury, as indicated by abnormal lipase or amylase;
  • urinary obstruction or difficulty in voiding.
• History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative