Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment

• ClinicalTrials.gov Identifier: NCT00447694
• Recruitment Status: Completed
• First Posted: March 15, 2007
• Results First Posted: June 7, 2021
• Last Update Posted: June 14, 2021
• Sponsor: Novartis
• Information provided by (Responsible Party): Novartis

Tracking Information

• First Submitted Date: March 13, 2007
• First Posted Date: March 15, 2007
• Results First Submitted Date: May 11, 2021
• Results First Posted Date: June 7, 2021
• Last Update Posted Date: June 14, 2021
• Study Start Date: February 2006
• Actual Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 11, 2021)

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).

• Original Primary Outcome Measures (submitted: March 13, 2007): Cardiac Iron in B thalassemia patients

Current Secondary Outcome Measures (submitted: May 11, 2021)

• 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).
• 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.
• 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.

Original Secondary Outcome Measures (submitted: March 13, 2007)

• Safety and tolerabilty of deferasirox
• Changes in liver iron concentration (LIC)
• Changes in ventricular ejection fraction
• Ferritin, NTBI (LPI and DCI)& iron metabolism parameters
• Compliance with deferasirox

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Beta-thalassemia
• Iron Overload

Intervention

Drug: Deferasirox

Oral deferasirox 30mg/kg/day once per day for 77 weeks.

Study Arms

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.

Intervention: Drug: Deferasirox

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 13, 2007): 30
• Original Enrollment: Same as current
• Actual Study Completion Date: November 2009
• Actual Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00447694
• Other Study ID Numbers: CICL670AUS04
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis
• Original Responsible Party: Not Provided
• Current Study Sponsor: Novartis
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Novartis
• Verification Date: June 2021