Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment

NCT00447694 | Completed Phase 2 Results

• 1 other identifier: CICL670AUS04
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

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.

Conditions

Beta-thalassemia; Iron Overload

Keywords

Iron Chelation; Deferasirox; Chelator; Desferal; beta-thalassemia; Iron overload

Outcome Measures

Primary Outcomes (1)

• 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).

  From Baseline to 25, 49, 77 Week

Secondary Outcomes (3)

• Change From Baseline in Liver Iron Concentration (LIC) Was Measured by MRI R2 From Absolute Change From Baseline to 101 Weeks

  From Baseline to 25, 49, 77 Week

• Left Ventricular Ejection Fraction (LVEF) and Change in Left Ventricular Ejection Fraction From Baseline to 101 Weeks

  From Baseline to 25, 49, 77 Week

• Serum Ferritin and Changes From Baseline in Serum Ferritin During Study

  From Baseline to 25, 49, 77 Week

Study Arms (1)

deferasirox every day for 77 weeks

EXPERIMENTAL

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

Interventions

Deferasirox DRUG

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

deferasirox every day for 77 weeks

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (3)

Childrens Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital and Research Center at Oakland

Oakland, California, 94609, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Related Publications (2)

• 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.

  PMID: 21393329 DERIVED

• 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.

  PMID: 20421452 DERIVED

Related Links

• Novartis Clinical Trial results website

MeSH Terms

Conditions

beta-Thalassemia; Iron Overload

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2007
• First Posted: March 15, 2007
• Study Start: February 1, 2006
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: June 14, 2021
• Results First Posted: June 7, 2021

Record last verified: 2021-06

Locations

US (3)