Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00117507
First received: June 30, 2005
Last updated: April 25, 2012
Last verified: April 2012

June 30, 2005
April 25, 2012
April 2005
January 2008   (final data collection date for primary outcome measure)
Safety and tolerability in myelodysplastic syndrome (MDS) patients [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
To evaluate the safety and tolerability of deferasirox 20 mg/kg/day over one year in MDS patients
Complete list of historical versions of study NCT00117507 on ClinicalTrials.gov Archive Site
  • Efficacy based on serum ferritin and Liver iron concentration (LIC) [ Time Frame: through out the study ] [ Designated as safety issue: No ]
  • Changes in liver iron concentration (LIC) [ Time Frame: through out the study ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (PK) in MDS patients [ Time Frame: through out the study ] [ Designated as safety issue: No ]
  • Non-transferrin bound iron (NTBI) & iron metabolism parameters [ Time Frame: through out the study ] [ Designated as safety issue: Yes ]
  • Iron metabolism parameters [ Time Frame: through out the study ] [ Designated as safety issue: Yes ]
  • 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
Not Provided
Not Provided
 
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 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.

Patients will be screened for eligibility to determine if they meet all inclusion/exclusion criteria. The screening period will be 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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Myelodysplastic Syndromes
  • Iron Overload
Drug: deferasirox
deferasirox 20 mg/kg/day taken over one year.Deferasirox should be taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets should be dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Other Names:
  • cheltor
  • iron chelator
Experimental: 20mg/kg/day deferasirox
Deferasirox will be administered orally once per day for 12 months. Surrogate marker findings, including serum ferritin, and LIC in the context of the study results will be monitored on a regular basis for any indications of clinically important over- or under-chelation.
Intervention: Drug: deferasirox
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
January 2008
January 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00117507
CICL670AUS02
No
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP