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
  Purpose

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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Safety and Tolerability Study of Deferasirox for Treatment of Transfusional Iron Overload in Low-Risk and INT-1 Myelodysplastic Patients

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Safety and tolerability in myelodysplastic syndrome (MDS) patients [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 24
Study Start Date: April 2005
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00117507

Locations
United States, California
Stanford University Medical Center
Stanford, California, United States, 94305-5821
United States, Michigan
Karmanos Cancer Center
Detroit, Michigan, United States, 48201
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00117507     History of Changes
Other Study ID Numbers: CICL670AUS02
Study First Received: June 30, 2005
Last Updated: April 25, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
MDS
Myelodysplastic Syndrome
ICL-670
ICL-670 and Myelodysplastic Syndrome

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Iron Overload
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Iron Metabolism Disorders
Metabolic Diseases
Chelating Agents
Deferasirox
Iron
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Iron Chelating Agents

ClinicalTrials.gov processed this record on April 17, 2014