Thalassemia Major With Severe Transfusional Iron OverloadPhase 1/2NCT01709032
Combination Deferasirox and Deferiprone for Severe Iron Overload in Thalassemia
A Phase 1/2 study testing Deferasirox and deferiprone in people with Thalassemia Major With Severe Transfusional Iron Overload, run by Children's Hospital of Philadelphia at 2 sites in United States.
Trial summary
We hypothesize that the combination treatment with deferasirox and deferiprone will be well tolerated and will result in significant improvement in cardiac and liver iron levels. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thalassemia Major With Severe Transfusional Iron Overload
- What is being tested?
- Deferasirox and deferiprone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2012to 1 Aug 2017
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Alpha or beta thalassemia
- Receiving chronic transfusions (at least 20 transfusions in lifetime) with iron overload requiring treatment with chelation
- Serum ferritin >500 ng/ml
- Liver iron concentration equal to or greater than 10 mg/g dw (by R2 MRI) or 7 to 10 mg/g dw (by R2 MRI) and not improving OR cardiac T2* between 6 and <20 ms
- Women of childbearing age must have a negative pregnancy test
- Agree to use approved method of contraception for the duration of the study
- Subjects must have a good understanding of the study and be willing to comply with study procedures
Who cannot join
- Subjects with past history of unexplained neutropenia (ANC < 1500/mcL), clinically significant renal disease (creatinine above the upper limit of normal), proteinuria >300 mg/L, clinically significant liver disease (ALT > 5x upper limit of normal), pulmonary or cardiovascular disease
- History of other clinically relevant oral, endocrine, neurologic, psychiatric, immunologic, bone marrow or skin disorder that contraindicates dosing with deferasirox or deferiprone
- History of adverse reaction or known allergy to either deferasirox or deferiprone necessitating drug discontinuation
- Currently receiving treatment for active hepatitis
- Use of any investigational agent in the past 30 days
- Cardiac T2* <6 ms, left ventricular ejection fraction < 56%, and/or arrhythmia (certain subjects may be eligible if they have already had a trial of deferoxamine and deferiprone). Subjects who refuse to use deferoxamine after extensive consultation with at least 2 health care providers will also be allowed to participate.
- Pregnant or breastfeeding females
- Unwilling or unable to comply with study related procedures
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Pilot Study of Deferasirox and Deferiprone Combination Oral Chelation for Individuals With Transfusion Dependent Thalassemia and High Iron Burden
We hypothesize that the combination treatment with deferasirox and deferiprone will be well tolerated and will result in significant improvement in cardiac and liver iron levels.
Read the detailed description
Death and disability from iron related damage to the heart remain the most serious issue facing transfusion-dependent patients with thalassemia. However, over the past decade there have been several reports of improved survival and fewer cardiac complications. This improvement may be related to the availability of three chelators and also the accurate measurement of iron stores in various organs (e.g. heart and liver) with magnetic resonance imaging, which allows for personalized, tailored medical care for patients. The chelator characteristics, side effect profiles, and ability to remove iron from specific organs differ among the chelators, suggesting that combination therapy may be beneficial. Using two drugs at lower doses may be more tolerable than escalating doses of a single drug and may improve iron removal. The combination of deferoxamine and deferiprone has been shown to be particularly beneficial for reducing cardiac iron, but it requires a painful injection/infusion, which hinders adherence. This pilot study aims to investigate the safety of an oral-only combination chelator regimen (deferasirox and deferiprone) in individuals with thalassemia major with poorly controlled iron overload and to assess how well this chelator combination lowers iron stores over one year.
- Being tested
- Deferasirox and deferiprone
- Keywords
- Thalassemia, Chelation, Transfusion, Safety
- Medical subject headings
- Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deferasirox and deferiproneDrug
Also called Exjade, Ferriprox
| Study group | Role | What they receive |
|---|---|---|
| Deferasirox and deferiprone | Experimental | Not described Receives: Drug: Deferasirox and deferiprone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Improvement in Liver Iron Concentration
Determine the safety of the combination of Deferasirox and Deferiprone for the treatment of subjects with Thalassemia Major and Severe Iron Overload by assessing change in liver iron concentration from baseline to follow-up
Measured: 12 months
Secondary outcomes (1)
Number of Participants With Improvement in Cardiac T2* MRI
Improvement in Cardiac T2* MRI from baseline to determine if there is a reduction of cardiac iron burden.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2012 (estimated)
- Study startSep 2012
- Primary completion1 Aug 2015
- Study completion1 Aug 2017
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.
- Other trials for Thalassemia Major With Severe Transfusional Iron OverloadStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- The Cooley's Anemia Foundation,, Ann & Robert H Lurie Children's Hospital of Chicago
- Responsible party
- Sponsor
- Investigators
- Janet L Kwiatkowski, MD, MSCE, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01709032
- Sponsor's protocol ID
- 12-009449
- Status last verified
- Feb 2019
- First submitted
- 16 Oct 2012
- Last updated
- 6 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Deferasirox and Deferiprone Combination Oral Chelation for Individuals With Transfusion Dependent Thalassemia and High Iron Burden
- ClinicalTrials.gov ID
- NCT01709032
- Acronym / sponsor ID
- 12-009449
- Keywords
- Thalassemia, Chelation, Transfusion, Safety
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- The Cooley's Anemia Foundation,, Ann & Robert H Lurie Children's Hospital of Chicago
- Study start
- Sep 2012 (actual)
- Primary completion
- 1 Aug 2015 (actual)
- Study completion
- 1 Aug 2017 (actual)
- First posted
- 17 Oct 2012 (estimated)
- Results
- Posted 6 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We hypothesize that the combination treatment with deferasirox and deferiprone will be well tolerated and will result in significant improvement in cardiac and liver iron levels.
Detailed description
Death and disability from iron related damage to the heart remain the most serious issue facing transfusion-dependent patients with thalassemia. However, over the past decade there have been several reports of improved survival and fewer cardiac complications. This improvement may be related to the availability of three chelators and also the accurate measurement of iron stores in various organs (e.g. heart and liver) with magnetic resonance imaging, which allows for personalized, tailored medical care for patients. The chelator characteristics, side effect profiles, and ability to remove iron from specific organs differ among the chelators, suggesting that combination therapy may be beneficial. Using two drugs at lower doses may be more tolerable than escalating doses of a single drug and may improve iron removal. The combination of deferoxamine and deferiprone has been shown to be particularly beneficial for reducing cardiac iron, but it requires a painful injection/infusion, which hinders adherence. This pilot study aims to investigate the safety of an oral-only combination chelator regimen (deferasirox and deferiprone) in individuals with thalassemia major with poorly controlled iron overload and to assess how well this chelator combination lowers iron stores over one year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Deferasirox and deferiprone | Experimental | Drug: Deferasirox and deferiprone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Alpha or beta thalassemia
- Receiving chronic transfusions (at least 20 transfusions in lifetime) with iron overload requiring treatment with chelation
- Serum ferritin >500 ng/ml
- Liver iron concentration equal to or greater than 10 mg/g dw (by R2 MRI) or 7 to 10 mg/g dw (by R2 MRI) and not improving OR cardiac T2* between 6 and <20 ms
- Women of childbearing age must have a negative pregnancy test
Key exclusion criteria (8 listed)
- Subjects with past history of unexplained neutropenia (ANC < 1500/mcL), clinically significant renal disease (creatinine above the upper limit of normal), proteinuria >300 mg/L, clinically significant liver disease (ALT > 5x upper limit of normal), pulmonary or cardiovascular disease
- History of other clinically relevant oral, endocrine, neurologic, psychiatric, immunologic, bone marrow or skin disorder that contraindicates dosing with deferasirox or deferiprone
- History of adverse reaction or known allergy to either deferasirox or deferiprone necessitating drug discontinuation
- Currently receiving treatment for active hepatitis
- Use of any investigational agent in the past 30 days
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 |
|---|---|---|
| Deferasirox and deferiproneAlso: Exjade, Ferriprox | Drug | Deferasirox and deferiprone |
Primary outcome
Number of Participants With Improvement in Liver Iron Concentration
Time frame: 12 months
Determine the safety of the combination of Deferasirox and Deferiprone for the treatment of subjects with Thalassemia Major and Severe Iron Overload by assessing change in liver iron concentration from baseline to follow-up
1 secondary outcome
Number of Participants With Improvement in Cardiac T2* MRI
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
Janet L Kwiatkowski, MD, MSCE principal investigator
Children's Hospital of Philadelphia
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Deferasirox and deferiprone in people with Thalassemia Major With Severe Transfusional Iron Overload, run by Children's Hospital of Philadelphia at 2 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 7 inclusion and 8 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 6 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 6 Mar 2019). 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?
Number of Participants With Improvement in Liver Iron Concentration (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Mar 2019.