Exjade-Early-Trial
Condition: Myelodysplastic Syndromes
MeSH terms: Myelodysplastic Syndromes
Intervention: Deferasirox (Novartis Pharma)
Intervention description: Treatment period 102 weeks. Starting dose 10mg/kg/day. Up to 30/mg/kg according to dose adjustment table as specified in the protocol
Intervention MeSH terms: Deferasirox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Study outline: Deferasirox (Exjade®) is regularly used in severe iron overload in order to
      avoid organ damage of liver, heart and other organs. It has been proposed, that iron overload
      may not only impose damage to other organs but also to the bone marrow and thus worsen
      hematopoietic insufficiency in patients with MDS. Patients presenting with low or INT-1 risk
      MDS with only mild iron overload will be treated with deferasirox in this study. It will be
      analyzed if hematological improvement can be observed during this treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  MDS of subtype RA, RARS, RCMD, RCMD-RS (i.e. lower risk)

          -  RAEB I allowed, if clinically stable for > 3 months

          -  5q-minus syndrome allowed, if lenalidomide unsuccessful or unavailable at the time of
             inclusion

          -  IPSS score < intermediate-1

          -  transfusion dependent or Hb < 10,5 g/dl

          -  History of less than 20 units of red blood cell transfusions or 100mL/kg of prepacked
             red blood cells (PRBCs), except for transfusions for acute bleeding

          -  Serum ferritin > 300 µg/l and < 1500 μg/l. This level should have been verified at
             least at two occasions within 3 months. Samples must be obtained in the absence of
             concomitant severe infection

          -  no indication for EPO (due to high endogenous EPO levels) or EPO without benefit in
             the past

          -  no indication and/or no plans for cytostatic drugs

          -  no previous exposure to cytostatic drugs, thalidomide, lenalidomide, G-CSF or EPO or
             exposure to any of these drugs has been terminated since > 8 weeks (4 weeks for
             G-CSF).

          -  no indication and/or no plans for stem cell transplantation

          -  stable or worsening cytopenia during the past 8 weeks. If in doubt, extend screening
             period to >= 8 weeks

          -  Patients of either gender and age > 18 years

          -  Life expectancy > 12 months

          -  Females of childbearing potential must use double-barrier contraception (for example
             orale contraception and condom).

          -  Mental ability of the patient to understand explications concerning the study and to
             understand and follow instructions of the investigating physician

          -  Written informed consent by the patient

        Exclusion Criteria:

          -  Treatment with deferasirox or other chelation therapy for periods > 4 weeks before
             study start

          -  Patients with intolerance to Deferasirox

          -  Patients with a concomitant second malignant disease, possibly interfering with life
             expectancy

          -  Patients with mean levels of alanine aminotransferase (ALT) > 5x ULN

          -  Patients with uncontrolled systemic hypertension

          -  Patients with serum creatinine > 1.5x the upper limit of normal (ULN) or a creatinine
             clearance < 60 ml/min according to the MDRD formula (Levey 2005)

          -  History of nephrotic syndrome

          -  Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent the
             patient from undergoing study treatment

          -  Patients with psychiatric or addictive disorders which prevent them from giving their
             informed consent or undergoing study treatment

          -  Patients treated with systemic investigational drugs within the past 4 weeks or
             topical investigational drug within the past 7 days

          -  Any 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:

          -  history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal
             bleeding;

          -  history of major gastrointestinal tract surgery such as gastrectomy,
             gastroenterostomy, or bowel resection;

          -  history of pancreatic injury or pancreatitis; indications of impaired pancreatic
             function/injury as indicated by abnormal lipase or amylase;

          -  history of urinary obstruction or difficulty in voiding

          -  History of non-compliance to medical regimens and patients who are considered
             potentially unreliable and/or not cooperative

          -  History of drug or alcohol abuse within the 12 months prior to dosing or evidence of
             such abuse as indicated by laboratory assays conducted during the screening period

          -  Patients with active uncontrolled infectious disease

          -  Pregnancy or breast feeding

          -  QT > 470 msec on screening ECG

          -  Patients with a history of Torsades de Pointes