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Combination Deferasirox and Deferiprone for Severe Iron Overload in Thalassemia

Primary Purpose

Thalassemia Major With Severe Transfusional Iron Overload

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Deferasirox and deferiprone
Sponsored by
Children's Hospital of Philadelphia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thalassemia Major With Severe Transfusional Iron Overload focused on measuring Thalassemia, Chelation, Transfusion, Safety

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Deferasirox and deferiprone

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Full Information

First Posted
October 16, 2012
Last Updated
February 13, 2019
Sponsor
Children's Hospital of Philadelphia
Collaborators
The Cooley's Anemia Foundation,, Ann & Robert H Lurie Children's Hospital of Chicago
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1. Study Identification

Unique Protocol Identification Number
NCT01709032
Brief Title
Combination Deferasirox and Deferiprone for Severe Iron Overload in Thalassemia
Official Title
Pilot Study of Deferasirox and Deferiprone Combination Oral Chelation for Individuals With Transfusion Dependent Thalassemia and High Iron Burden
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
September 2012 (Actual)
Primary Completion Date
August 1, 2015 (Actual)
Study Completion Date
August 1, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital of Philadelphia
Collaborators
The Cooley's Anemia Foundation,, Ann & Robert H Lurie Children's Hospital of Chicago

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thalassemia Major With Severe Transfusional Iron Overload
Keywords
Thalassemia, Chelation, Transfusion, Safety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Deferasirox and deferiprone
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Deferasirox and deferiprone
Other Intervention Name(s)
Exjade, Ferriprox
Primary Outcome Measure Information:
Title
Number of Participants With Improvement in Liver Iron Concentration
Description
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
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Number of Participants With Improvement in Cardiac T2* MRI
Description
Improvement in Cardiac T2* MRI from baseline to determine if there is a reduction of cardiac iron burden.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janet L Kwiatkowski, MD, MSCE
Organizational Affiliation
Children's Hospital of Philadlephia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

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Combination Deferasirox and Deferiprone for Severe Iron Overload in Thalassemia

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