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The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) Study

Phase 2
2 Years
Not Enrolling

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Trial Information

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

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.

Inclusion Criteria:

- Age greater than 2 years.

- Proven or probable invasive mucormycosis, as defined by modification of consensus
European Organization for Research and Treatment of Cancer (EORTC)/Mycosis Study
Group (MSG) criteria. In brief, proven mucormycosis is defined as: 1)
histopathologic or cytopathologic examination showing broad-based, aseptate,
ribbon-like hyphae consistent with Mucorales from needle aspiration or biopsy
specimen, with evidence of associated tissue damage (either microscopically or
unequivocally by imaging); OR 2) a positive culture result for a sample obtained by
sterile procedure from normally sterile and clinically or radiologically abnormal
site consistent with infection, excluding urine and mucous membranes. Probable
mucormycosis is defined as: 1) an at-risk host; AND 2) positive culture, cytology, or
polymerase chain reaction (PCR) test (run at a CLIA-certified clinical microbiology
laboratory) from sputum, bronchoalveolar lavage (BAL), endoscopy/colonoscopy, or
sinus aspirate/biopsy; AND 3) 1 major or 2 minor clinical criteria.

- Radiographic study by Computerized Tomography (CT) or Magnetic Resonance Imaging
(MRI) has been obtained within 4 calendar days prior to enrollment and shows evidence
of infection (i.e. focal nodule, mass, or abscess, or enhancement, or evidence of
tissue edema or destruction that is not attributed to post-surgical reaction).

- Subject or authorized decision maker able to provide informed consent.

Exclusion Criteria:

- High likelihood of death within the 48 h after enrollment (investigator's

- High likelihood of death due to factors unrelated to mucormycosis (e.g. due to
uncontrolled and/or relapsed malignancy, severe graft versus host disease, other
underlying diseases, etc.) within 30 days following enrollment (investigator's

- Patient unable to receive enteral medication (oral or via feeding tube).

- Infection limited to the supra-fascial skin (skin lesions in the presence of
disseminated disease, deep invasive tissue infection spreading from a primary skin
site, or subcutaneous infections extending to fascia are allowed).

- Patient has received > 14 days of polyene antifungal therapy (i.e. amphotericin B
deoxycholate, liposomal amphotericin B, amphotericin B lipid complex, or amphotericin
B colloidal dispersion) at the time of screening.

- Patient is already taking deferasirox therapy for any reason at the time of

- Patient is allergic to or intolerant of deferasirox or LAmB.

- Patient has significant renal dysfunction at the time of screening, defined as serum
creatinine of > 3 mg/dL or a calculated creatinine clearance of < 30 ml/min (by the
Cockroft-Gault formula: (140 - age (yrs) * wt (kg)) * 0.85 (for females) / (72 *
serum creatinine (mg/dL)).

- Patient has significant hepatic dysfunction at the time of screening, defined as BOTH
an AST or ALT > 10 times the upper limit of normal, AND a direct (not total)
bilirubin > 5 times the upper limit of normal.

- Women of child-bearing potential (those with menses within the last year) with a
positive serum pregnancy test.

- Enrollment refused by the primary physician.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Safety and Tolerability of Adjunctive Deferasirox Therapy in Patients Being Treated With LAmB for Mucormycosis

Outcome Time Frame:

14 days

Safety Issue:


Principal Investigator

Brad Spellberg, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Los Angeles Biomedical Research Institute


United States: Institutional Review Board

Study ID:




Start Date:

October 2007

Completion Date:

December 2010

Related Keywords:

  • Mucormycosis
  • zygomycosis
  • Rhizopus
  • iron
  • iron-chelation
  • adjunctive therapy
  • Mucormycosis
  • Zygomycosis



MD Anderson Cancer CenterHouston, Texas  77030-4096
UCSFSan Francisco, California  941430324
Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
City of Hope National Medical CenterLos Angeles, California  91010
Duke UniversityDurham, North Carolina  27710
University of MiamiMiami, Florida  33136
Summa Health SystemsAkron, Ohio  44304