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Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment

Primary Purpose

Beta-thalassemia, Iron Overload

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Deferasirox
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Beta-thalassemia focused on measuring Iron Chelation, Deferasirox, Chelator, Desferal, beta-thalassemia, Iron overload

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female β-thalassemia outpatients on chronic transfusion therapy (defined as > 8 transfusions per year)
  • Lifetime minimum of 100 previous packed red blood cell transfusions
  • Patients currently on chelation therapy will require a one day wash out prior to the first dose of study drug
  • Age ≥ 10 years
  • Sexually active females of childbearing potential must have a negative serum or urine pregnancy test and use an effective method of contraception, or must have undergone clinically documented total hysterectomy.

Exclusion Criteria:

  • Ejection Fraction < 56 % measured using steady-state free precession imaging by MRI
  • Contraindication to MRI, including cardiac pacemaker, brain aneurysm clip, implanted neurostimulator, insulin pump, cochlear implant, metal slivers in the eyes, intrauterine device or any other MRI incompatible metal implants or intractable claustrophobia
  • Abnormal laboratory values as defined by the protocol
  • Clinical or laboratory evidence of active Hepatitis B or Hepatitis C
  • History of HIV positive test result (ELISA or Western blot)
  • Uncontrolled systemic hypertension
  • Second or third degree A-V block
  • Life-threatening arrhythmias, including sustained ventricular tachycardia and aborted sudden death, within the last year
  • History of cardiac conditions or unstable cardiac disease not controlled by standard medical therapy
  • 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 (documented negative pregnancy test required for study entry)
  • Patients enrolled in an ongoing clinical trial of deferasirox (ICL670) cannot be withdrawn in order to participate in this study
  • Treatment with systemic investigational drug within the past 4 weeks or 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
  • History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative
  • Other inclusion/exclusion criteria may apply

Sites / Locations

  • Childrens Hospital of Los Angeles
  • Children's Hospital and Research Center at Oakland
  • Children's Memorial Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

deferasirox every day for 77 weeks

Arm Description

Participants received Deferasirox 30 milligrams per kilogram per day (mg/kg/day) orally once daily (OD), 30 minutes before breakfast, preferably around the same time every morning if possible. Deferasirox tablets were dropped into water or orange juice, or apple juice and stirred until completely dispersed. For doses less than 1 gram (g), tablets were dissolved in at least 100 milliliter (mL) of liquid; for doses of 1 to 3 g, tablets were dissolved in at least 200 mL. After tablets were fully disintegrated, the liquid was promptly consumed.

Outcomes

Primary Outcome Measures

Magnetic Resonance Imaging (MRI) T2* and Absolute Change From Baseline in MRI T2*
Cardiac T2* was measured in the short axis plane at the widest point of a 4-chamber localizer using custom breath-hold R2* gradient echo sequences modeled after techniques used by Anderson et al (2001) and Westwood et al (2003).

Secondary Outcome Measures

Change From Baseline in Liver Iron Concentration (LIC) Was Measured by MRI R2 From Absolute Change From Baseline to 101 Weeks
MRI evaluation of liver iron concentration has been validated by liver biopsy (St Pierre et al 2005). Studies comparing T2* values of liver iron concentration (LIC) with LIC as assessed by biopsy have confirmed that T2* values reflect liver iron content (Wood et al 2003b). Direct tissue-validation of cardiac T2* measurements in humans has not been performed because endomyocardial biopsy is a dangerous and unreliable indicator of cardiac iron overload (Olson et al 1989, Fitchett et al 1980). However, it has been shown that cardiac T2* accurately reflects cardiac iron in a gerbil iron cardiomyopathy model (Wood et al 2004b). T2* measurements have shown excellent inter-scanner and inter-exam reproducibility, making them suitable for longitudinal monitoring (Westwood et al 2003a, Westwood et al 2003b).
Left Ventricular Ejection Fraction (LVEF) and Change in Left Ventricular Ejection Fraction From Baseline to 101 Weeks
Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader.
Serum Ferritin and Changes From Baseline in Serum Ferritin During Study
Serum ferritin will be assessed at each study visit. Analysis was performed in Completer population consists of those participants who had a Week 77 MRI.

Full Information

First Posted
March 13, 2007
Last Updated
June 8, 2021
Sponsor
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00447694
Brief Title
Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment
Official Title
An Open Label Trial Evaluating Cardiac T2* in Beta-thalassemia Patients on Deferasirox (ICL670) Treatment for 18 Months
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
February 2006 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis

4. Oversight

5. Study Description

Brief Summary
The purpose of this trial is to evaluate changes in cardiac iron as measured by MRI T2* in beta-thalassemia patients with deferasirox treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Beta-thalassemia, Iron Overload
Keywords
Iron Chelation, Deferasirox, Chelator, Desferal, beta-thalassemia, Iron overload

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
deferasirox every day for 77 weeks
Arm Type
Experimental
Arm Description
Participants received Deferasirox 30 milligrams per kilogram per day (mg/kg/day) orally once daily (OD), 30 minutes before breakfast, preferably around the same time every morning if possible. Deferasirox tablets were dropped into water or orange juice, or apple juice and stirred until completely dispersed. For doses less than 1 gram (g), tablets were dissolved in at least 100 milliliter (mL) of liquid; for doses of 1 to 3 g, tablets were dissolved in at least 200 mL. After tablets were fully disintegrated, the liquid was promptly consumed.
Intervention Type
Drug
Intervention Name(s)
Deferasirox
Intervention Description
Oral deferasirox 30mg/kg/day once per day for 77 weeks.
Primary Outcome Measure Information:
Title
Magnetic Resonance Imaging (MRI) T2* and Absolute Change From Baseline in MRI T2*
Description
Cardiac T2* was measured in the short axis plane at the widest point of a 4-chamber localizer using custom breath-hold R2* gradient echo sequences modeled after techniques used by Anderson et al (2001) and Westwood et al (2003).
Time Frame
From Baseline to 25, 49, 77 Week
Secondary Outcome Measure Information:
Title
Change From Baseline in Liver Iron Concentration (LIC) Was Measured by MRI R2 From Absolute Change From Baseline to 101 Weeks
Description
MRI evaluation of liver iron concentration has been validated by liver biopsy (St Pierre et al 2005). Studies comparing T2* values of liver iron concentration (LIC) with LIC as assessed by biopsy have confirmed that T2* values reflect liver iron content (Wood et al 2003b). Direct tissue-validation of cardiac T2* measurements in humans has not been performed because endomyocardial biopsy is a dangerous and unreliable indicator of cardiac iron overload (Olson et al 1989, Fitchett et al 1980). However, it has been shown that cardiac T2* accurately reflects cardiac iron in a gerbil iron cardiomyopathy model (Wood et al 2004b). T2* measurements have shown excellent inter-scanner and inter-exam reproducibility, making them suitable for longitudinal monitoring (Westwood et al 2003a, Westwood et al 2003b).
Time Frame
From Baseline to 25, 49, 77 Week
Title
Left Ventricular Ejection Fraction (LVEF) and Change in Left Ventricular Ejection Fraction From Baseline to 101 Weeks
Description
Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader.
Time Frame
From Baseline to 25, 49, 77 Week
Title
Serum Ferritin and Changes From Baseline in Serum Ferritin During Study
Description
Serum ferritin will be assessed at each study visit. Analysis was performed in Completer population consists of those participants who had a Week 77 MRI.
Time Frame
From Baseline to 25, 49, 77 Week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female β-thalassemia outpatients on chronic transfusion therapy (defined as > 8 transfusions per year) Lifetime minimum of 100 previous packed red blood cell transfusions Patients currently on chelation therapy will require a one day wash out prior to the first dose of study drug Age ≥ 10 years Sexually active females of childbearing potential must have a negative serum or urine pregnancy test and use an effective method of contraception, or must have undergone clinically documented total hysterectomy. Exclusion Criteria: Ejection Fraction < 56 % measured using steady-state free precession imaging by MRI Contraindication to MRI, including cardiac pacemaker, brain aneurysm clip, implanted neurostimulator, insulin pump, cochlear implant, metal slivers in the eyes, intrauterine device or any other MRI incompatible metal implants or intractable claustrophobia Abnormal laboratory values as defined by the protocol Clinical or laboratory evidence of active Hepatitis B or Hepatitis C History of HIV positive test result (ELISA or Western blot) Uncontrolled systemic hypertension Second or third degree A-V block Life-threatening arrhythmias, including sustained ventricular tachycardia and aborted sudden death, within the last year History of cardiac conditions or unstable cardiac disease not controlled by standard medical therapy 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 (documented negative pregnancy test required for study entry) Patients enrolled in an ongoing clinical trial of deferasirox (ICL670) cannot be withdrawn in order to participate in this study Treatment with systemic investigational drug within the past 4 weeks or 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 History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative Other inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Coates, MD
Organizational Affiliation
Childresn's Hospital of Los Angeles
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alexis Thompson, MD
Organizational Affiliation
Children's Memorial Hospital of Chicago
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paul Harmatz, MD
Organizational Affiliation
Children's Hospital and Research Center at Oakland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Childrens Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital and Research Center at Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Children's Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21393329
Citation
Wood JC, Glynos T, Thompson A, Giardina P, Harmatz P, Kang BP, Paley C, Coates TD. Relationship between labile plasma iron, liver iron concentration and cardiac response in a deferasirox monotherapy trial. Haematologica. 2011 Jul;96(7):1055-8. doi: 10.3324/haematol.2010.032862. Epub 2011 Mar 10.
Results Reference
derived
PubMed Identifier
20421452
Citation
Wood JC, Kang BP, Thompson A, Giardina P, Harmatz P, Glynos T, Paley C, Coates TD. The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores. Blood. 2010 Jul 29;116(4):537-43. doi: 10.1182/blood-2009-11-250308. Epub 2010 Apr 26.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=3642
Description
Novartis Clinical Trial results website

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Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment

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