Combination Deferasirox and Deferiprone for Severe Iron Overload in Thalassemia

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.

Study Overview

• Status: Completed
• Conditions: Thalassemia Major With Severe Transfusional Iron Overload
• Intervention / Treatment: Drug: Deferasirox and deferiprone

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Deferasirox and deferiprone	Drug: Deferasirox and deferiprone; Other Names: Exjade; Ferriprox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: Ann & Robert H Lurie Children's Hospital of Chicago; The Cooley's Anemia Foundation,
• Investigators: Principal Investigator: Janet L Kwiatkowski, MD, MSCE, Children's Hospital of Philadlephia

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2012
• Primary Completion (ACTUAL): August 1, 2015
• Study Completion (ACTUAL): August 1, 2017

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 16, 2012
• First Posted (ESTIMATE): October 17, 2012

Study Record Updates

• Last Update Posted (ACTUAL): March 6, 2019
• Last Update Submitted That Met QC Criteria: February 13, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Thalassemia; Transfusion; Chelation
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Iron Metabolism Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Iron Overload; Thalassemia; beta-Thalassemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox; Deferiprone
• Other Study ID Numbers: 12-009449