Thirty patients will be 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 will have low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria. All patients will initiate treatment with 20mg/kg/day deferasirox. Deferasirox will be administered orally once per day for 12 months.

Condition	Intervention	Phase
Myelodysplastic Syndromes Iron Overload	Drug: deferasirox	Phase II

Further Study Details: 

Primary Outcomes: To evaluate the safety and tolerability of deferasirox 20 mg/kg/day over one year in MDS patients
Secondary Outcomes: To evaluate the efficacy of deferasirox based on changes in serum ferritin from baseline to 3, 6, 9 and 12 months after initiation of treatment; To estimate absolute and relative change in liver iron concentration (LIC) from baseline to 6 and 12 months, assessed using liver MRI R2; To evaluate change in transfusion requirements, serum erythropoietin levels, and hematologic parameters; To evaluate the pharmacokinetics (PK) of deferasirox in MDS patients; To evaluate the role of nontransferrin bound iron [NTBI] (LPI and DCI), serum iron, transferrin and transferrin saturation on the safe administration of deferasirox; To assess drug accountability with the administration of oral deferasirox
Expected Total Enrollment:  30

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00117507

Novartis Oncology Clinical Trials Call Center      800-340-6843 

California
      Stanford University Medical Center, Stanford,  California,  94305-5821,  United States; Not yet recruiting
Michigan
      Karmanos Cancer Center, Detroit,  Michigan,  48201,  United States; Recruiting
Texas
      MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States; Not yet recruiting

Study ID Numbers:  CICL670A US02
Record last reviewed:  July 2005
Last Updated:  July 14, 2005
Record first received:  July 6, 2005
ClinicalTrials.gov Identifier:  NCT00117507
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-07-26