Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients
Condition: Myelodysplastic Syndromes; Iron Overload
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Iron Overload; Syndrome
Intervention: Deferasirox
Intervention MeSH terms: Deferasirox; Chelating Agents
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MDS; Myelodysplastic Syndrome; ICL-670; ICL-670 and Myelodysplastic Syndrome

Summary:

      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.
    

Eligibility criteria:

        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