Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment

June 8, 2021 updated by: Novartis

An Open Label Trial Evaluating Cardiac T2* in Beta-thalassemia Patients on Deferasirox (ICL670) Treatment for 18 Months

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Childrens Hospital of Los Angeles
      • Oakland, California, United States, 94609
        • Children's Hospital and Research Center at Oakland
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: deferasirox every day for 77 weeks
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.
Drug: Deferasirox
Oral deferasirox 30mg/kg/day once per day for 77 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Magnetic Resonance Imaging (MRI) T2* and Absolute Change From Baseline in MRI T2*
Time Frame: From Baseline to 25, 49, 77 Week
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).
From Baseline to 25, 49, 77 Week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Liver Iron Concentration (LIC) Was Measured by MRI R2 From Absolute Change From Baseline to 101 Weeks
Time Frame: From Baseline to 25, 49, 77 Week
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).
From Baseline to 25, 49, 77 Week
Left Ventricular Ejection Fraction (LVEF) and Change in Left Ventricular Ejection Fraction From Baseline to 101 Weeks
Time Frame: From Baseline to 25, 49, 77 Week
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.
From Baseline to 25, 49, 77 Week
Serum Ferritin and Changes From Baseline in Serum Ferritin During Study
Time Frame: From Baseline to 25, 49, 77 Week
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.
From Baseline to 25, 49, 77 Week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis

Investigators

  • Principal Investigator: Thomas Coates, MD, Childresn's Hospital of Los Angeles
  • Principal Investigator: Paul Harmatz, MD, Children's Hospital and Research Center at Oakland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2006

Primary Completion (ACTUAL)

November 1, 2009

Study Completion (ACTUAL)

November 1, 2009

Study Registration Dates

First Submitted

March 13, 2007

First Submitted That Met QC Criteria

March 13, 2007

First Posted (ESTIMATE)

March 15, 2007

Study Record Updates

Last Update Posted (ACTUAL)

June 14, 2021

Last Update Submitted That Met QC Criteria

June 8, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CICL670AUS04

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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