Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients

An Open Label, Safety and Tolerability Study of Deferasirox for Treatment of Transfusional Iron Overload in Low-Risk and INT-1 Myelodysplastic Patients

Thirty patients were to be enrolled and 24 patients were actually enrolled into this open-label, single-arm trial designed to assess the safety and tolerability of oral deferasirox in adult transfusion dependent myelodysplastic syndrome (MDS) patients with iron overload. Patients enrolled in this study had low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria. All patients initiated treatment with 20mg/kg/day deferasirox.

Deferasirox were administered orally once per day for 12 months.

Patients were screened for eligibility to determine if they meet all inclusion/exclusion criteria. The screening period were up to 4 weeks. Patient's baseline LIC will be determined non-invasively by means of MRI R2 analysis. In addition, blood and urine samples will be taken for the determination of baseline safety data.

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 on chelation therapy at the time of screening required a 1-day wash out prior to the first dose of study drug.

• 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 20 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 greater than 2 × upper limit of normal (ULN)

• ALT or AST greater than 5 × ULN.

• 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

• 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