Combination Deferasirox and Deferiprone for Severe Iron Overload in Thalassemia

Sponsor
Children's Hospital of Philadelphia (Other)
Overall Status
Completed
CT.gov ID
NCT01709032
Collaborator
The Cooley's Anemia Foundation, (Other), Ann & Robert H Lurie Children's Hospital of Chicago (Other)
9
2
1
59
4.5
0.1

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Deferasirox and deferiprone
Phase 1/Phase 2

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

Study Type:
Interventional
Actual Enrollment :
9 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Pilot Study of Deferasirox and Deferiprone Combination Oral Chelation for Individuals With Transfusion Dependent Thalassemia and High Iron Burden
Actual Study Start Date :
Sep 1, 2012
Actual Primary Completion Date :
Aug 1, 2015
Actual Study Completion Date :
Aug 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Deferasirox and deferiprone

Drug: Deferasirox and deferiprone
Other Names:
  • Exjade
  • Ferriprox
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Improvement in Liver Iron Concentration [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

    Secondary Outcome Measures

    1. Number of Participants With Improvement in Cardiac T2* MRI [12 months]

      Improvement in Cardiac T2* MRI from baseline to determine if there is a reduction of cardiac iron burden.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois United States 60611
    2 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104

    Sponsors and Collaborators

    • Children's Hospital of Philadelphia
    • The Cooley's Anemia Foundation,
    • Ann & Robert H Lurie Children's Hospital of Chicago

    Investigators

    • Principal Investigator: Janet L Kwiatkowski, MD, MSCE, Children's Hospital of Philadlephia

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Children's Hospital of Philadelphia
    ClinicalTrials.gov Identifier:
    NCT01709032
    Other Study ID Numbers:
    • 12-009449
    First Posted:
    Oct 17, 2012
    Last Update Posted:
    Mar 6, 2019
    Last Verified:
    Feb 1, 2019
    Keywords provided by Children's Hospital of Philadelphia
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Deferasirox and Deferiprone
    Arm/Group Description Deferasirox and deferiprone
    Period Title: Overall Study
    STARTED 9
    COMPLETED 6
    NOT COMPLETED 3

    Baseline Characteristics

    Arm/Group Title Deferasirox and Deferiprone
    Arm/Group Description Deferasirox and deferiprone
    Overall Participants 9
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    28.9
    (5.6)
    Sex: Female, Male (Count of Participants)
    Female
    5
    55.6%
    Male
    4
    44.4%
    Region of Enrollment (Count of Participants)
    United States
    9
    100%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Number with participants with improvement in liver iron concentration
    Arm/Group Title Deferasirox and Deferiprone
    Arm/Group Description Deferasirox and deferiprone
    Measure Participants 6
    Count of Participants [Participants]
    3
    33.3%
    2. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Number of participants with improvement
    Arm/Group Title Deferasirox and Deferiprone Combination Chelation
    Arm/Group Description Deferasirox and deferiprone
    Measure Participants 6
    Count of Participants [Participants]
    3
    33.3%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Deferasirox and Deferiprone
    Arm/Group Description Deferasirox and deferiprone
    All Cause Mortality
    Deferasirox and Deferiprone
    Affected / at Risk (%) # Events
    Total 0/9 (0%)
    Serious Adverse Events
    Deferasirox and Deferiprone
    Affected / at Risk (%) # Events
    Total 3/9 (33.3%)
    Gastrointestinal disorders
    Rectal bleeding from hemorrhoid 1/9 (11.1%) 1
    General disorders
    viral syndrome 1/9 (11.1%) 1
    Infections and infestations
    perirectal abscess 1/9 (11.1%) 2
    Other (Not Including Serious) Adverse Events
    Deferasirox and Deferiprone
    Affected / at Risk (%) # Events
    Total 8/9 (88.9%)
    Ear and labyrinth disorders
    Tinnitus 1/9 (11.1%) 1
    Gastrointestinal disorders
    Diarrhea 4/9 (44.4%) 4
    Nausea/vomiting 3/9 (33.3%) 3
    Abdominal pain 2/9 (22.2%) 3
    Hepatobiliary disorders
    ALT elevated 1/9 (11.1%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 4/9 (44.4%) 7

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Janet Kwiatkowski, MD
    Organization Children's Hospital of Philadelphia
    Phone 215-590-3437
    Email kwiatkowski@email.chop.edu
    Responsible Party:
    Children's Hospital of Philadelphia
    ClinicalTrials.gov Identifier:
    NCT01709032
    Other Study ID Numbers:
    • 12-009449
    First Posted:
    Oct 17, 2012
    Last Update Posted:
    Mar 6, 2019
    Last Verified:
    Feb 1, 2019