The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) Study
Because of its extremely high morbidity and mortality, it is imperative to look for new
antifungal therapies to treat mucormycosis. The agents of mucormycosis are exquisitely
sensitive to iron availability, and we and others have demonstrated that iron chelation
therapy improves the survival of rodents with mucormycosis. Deferasirox (Exjade) is the
first orally bioavailable iron chelator approved for use in the United States (US) by the
Food and Drug Administration (FDA), with an indication for treatment of iron overload from
chronic transfusions. In clinical studies, deferasirox has been well tolerated and
effective in iron-overloaded patients.
Although the safety and efficacy of deferasirox have been extensively evaluated in
iron-overloaded patients, there are minimal data in non-iron-overloaded patients or in
infected patients. Therefore, the safety and efficacy of deferasirox in patients with
mucormycosis is unclear, and confirming safety in the current study, at the currently
planned dose, is required to lay the groundwork for a future phase III clinical trial.
This is a prospective, phase II, randomized, double-blinded, placebo-controlled study of
liposomal amphotericin B (LAmB; AmBisome) plus deferasirox vs. LAmB plus placebo for
mucormycosis infection. Twenty patients with proven or probable mucormycosis (except for
isolated skin infection) by consensus EORTC/MSG criteria, who have received less than 14
days of antifungal therapy for mucormycosis, and who have had radiographic imaging by CT or
MRI within the past 72 hours that shows evidence of infection, will be randomized to receive
LAmB plus deferasirox or placebo (n = 10 per arm), with randomization stratified by study
site.
The primary objective is to determine the safety and tolerability of adjunctive deferasirox
therapy in patients being treated with LAmB for mucormycosis, and to obtain exploratory data
on the efficacy of the iron chelation treatment. The exploratory efficacy endpoint will be
the global response rate (composite of clinical and radiographic response) at end of study
drug administration, as determined by a blinded adjudication committee.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Safety and Tolerability of Adjunctive Deferasirox Therapy in Patients Being Treated With LAmB for Mucormycosis
14 days
Yes
Brad Spellberg, MD
Principal Investigator
Los Angeles Biomedical Research Institute
United States: Institutional Review Board
12842
NCT00419770
October 2007
December 2010
Name | Location |
---|---|
MD Anderson Cancer Center | Houston, Texas 77030-4096 |
UCSF | San Francisco, California 941430324 |
Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
City of Hope National Medical Center | Los Angeles, California 91010 |
Duke University | Durham, North Carolina 27710 |
University of Miami | Miami, Florida 33136 |
Summa Health Systems | Akron, Ohio 44304 |