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The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) Study
This study is currently recruiting participants.
Verified by Los Angeles Biomedical Research Institute, October 2008
Sponsors and Collaborators: Los Angeles Biomedical Research Institute
Gilead Sciences
Astellas Pharma Inc
Novartis
Information provided by: Los Angeles Biomedical Research Institute
ClinicalTrials.gov Identifier: NCT00419770
  Purpose

The purpose of this study is to determine if the addition of the medication, deferasirox, to standard antifungal therapy for the infection, mucormycosis, is safe and effective


Condition Intervention Phase
Mucormycosis
Drug: deferasirox
Phase II

Drug Information available for: Deferasirox Amphotericin B
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) Study

Further study details as provided by Los Angeles Biomedical Research Institute:

Primary Outcome Measures:
  • Safety and tolerability of adjunctive deferasirox therapy in patients being treated with LAmB for mucormycosis [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • Global response rate (composite of clinical and radiographic response) at end of study drug administration, as determined by a blinded adjudication committee [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Deferasirox pharmacokinetic and pharmacodynamic parameters [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Survival, radiographic improvement, clinical response, time to survival, deferasirox vs. free iron level correlation [ Time Frame: Up to 90 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: October 2007
Estimated Study Completion Date: May 2009
Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
B: Experimental
Deferasirox
Drug: deferasirox
20 mg/kg enterally per day

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 discretion).
  • 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 discretion).
  • 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 screening.
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00419770

Contacts
Contact: Brad Spellberg, MD 310-222-5381 bspellberg@labiomed.org

Locations
United States, California
UCSF Recruiting
San Francisco, California, United States, 94143
Principal Investigator: Peter Chin-Hong, MD            
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Mary Ann Clouser     626-256-4673 ext 62340     MClouser@coh.org    
Principal Investigator: James Ito, MD            
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Gabriel Blashke     305-585-7624     GBlaschke@med.miami.edu    
Principal Investigator: Michele Morris, MD            
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Elizabeth Dodds, PharmD         dodds002@mc.duke.edu    
Principal Investigator: John Perfect, MD            
United States, Ohio
Summa Health Systems Recruiting
Akron, Ohio, United States, 44304
Contact: Sara-Jane Salstrom     330-375-4293     salstros@summa-health.org    
Principal Investigator: Hector Bonilla, MD            
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Stacie Wright, RN     713-792-2095     slwright@mdanderson.org    
Principal Investigator: Dimitrios Kontoyiannis, MD            
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Judy Schramm, RN     206-667-4872        
Principal Investigator: David Fredericks, MD            
Sponsors and Collaborators
Los Angeles Biomedical Research Institute
Gilead Sciences
Astellas Pharma Inc
Novartis
Investigators
Principal Investigator: Brad Spellberg, MD Los Angeles Biomedical Research Institute
  More Information

Publications:
Responsible Party: Los Angeles Biomedical Research Institute ( Brad Spellberg, MD )
Study ID Numbers: 12842
Study First Received: January 5, 2007
Last Updated: October 17, 2008
ClinicalTrials.gov Identifier: NCT00419770  
Health Authority: United States: Institutional Review Board

Keywords provided by Los Angeles Biomedical Research Institute:
zygomycosis
Rhizopus
iron
iron-chelation
adjunctive therapy

Study placed in the following topic categories:
Abelcet
Amphotericin B
Mycoses
Deferasirox
Mucormycosis
Liposomal amphotericin B
Iron
Zygomycosis

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Iron Chelating Agents
Chelating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009