Beta-thalassemiaPhase 2NCT00447694
Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment
A Phase 2 study testing Deferasirox in people with Beta-thalassemia and Iron Overload, run by Novartis at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Beta-thalassemia, Iron Overload
- What is being tested?
- Deferasirox
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2006to Nov 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Children's Memorial Hospital
Chicago, Illinois, 60614
Childrens Hospital of Los Angeles
Los Angeles, California, 90027
Children's Hospital and Research Center at Oakland
Oakland, California, 94609
About this study
Official title: 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.
- Conditions
- Beta-thalassemia, Iron Overload
- Being tested
- Deferasirox
- Keywords
- Iron Chelation, Deferasirox, Chelator, Desferal, beta-thalassemia, Iron overload
- Medical subject headings
- beta-Thalassemia, Iron Overload
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DeferasiroxDrug
Oral deferasirox 30mg/kg/day once per day for 77 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Deferasirox |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
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).
Measured: From Baseline to 25, 49, 77 Week
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.
Measured: From Baseline to 25, 49, 77 Week
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.
Measured: From Baseline to 25, 49, 77 Week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2007 (estimated)
- Study startFeb 2006
- Primary completionNov 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Beta-thalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Thomas Coates, MD, Principal investigator, Childresn's Hospital of Los AngelesAlexis Thompson, MD, Principal investigator, Children's Memorial Hospital of ChicagoPaul Harmatz, MD, Principal investigator, Children's Hospital and Research Center at Oakland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00447694
- Sponsor's protocol ID
- CICL670AUS04
- Status last verified
- Jun 2021
- First submitted
- 13 Mar 2007
- Last updated
- 14 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 21393329Wood 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.
PubMed 20421452
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Trial Evaluating Cardiac T2* in Beta-thalassemia Patients on Deferasirox (ICL670) Treatment for 18 Months
- ClinicalTrials.gov ID
- NCT00447694
- Acronym / sponsor ID
- CICL670AUS04
- Conditions
- Beta-thalassemia, Iron Overload
- Keywords
- Iron Chelation, Deferasirox, Chelator, Desferal, beta-thalassemia, Iron overload
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Feb 2006
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 15 Mar 2007 (estimated)
- Results
- Posted 7 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| deferasirox every day for 77 weeks | Experimental | Drug: DeferasiroxParticipants 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. |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DeferasiroxOral deferasirox 30mg/kg/day once per day for 77 weeks. | Drug | deferasirox every day for 77 weeks |
Primary outcome
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).
3 secondary outcomes
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
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
Serum Ferritin and Changes From Baseline in Serum Ferritin During Study
Time frame: From Baseline to 25, 49, 77 Week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21393329Wood 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.
- Derived from this study: PubMed 20421452Wood 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.
- Novartis Clinical Trial results websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Coates, MD principal investigator
Childresn's Hospital of Los Angeles
Alexis Thompson, MD principal investigator
Children's Memorial Hospital of Chicago
Paul Harmatz, MD principal investigator
Children's Hospital and Research Center at Oakland
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Deferasirox in people with Beta-thalassemia and Iron Overload, run by Novartis at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Magnetic Resonance Imaging (MRI) T2* and Absolute Change From Baseline in MRI T2* (time frame: From Baseline to 25, 49, 77 Week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00447694, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2021.