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

This study has been completed.
Sponsor:
Collaborators:
Gilead Sciences
Astellas Pharma Inc
Novartis
Information provided by (Responsible Party):
Los Angeles Biomedical Research Institute
ClinicalTrials.gov Identifier:
NCT00419770
First received: January 5, 2007
Last updated: September 2, 2011
Last verified: August 2011
  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
Drug: Placebo
Drug: Liposomal amphotericin B
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) Study

Resource links provided by NLM:


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 ]
  • Total Adverse Events [ Time Frame: 30 Days After End of Therapy ] [ Designated as safety issue: Yes ]

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 ]

Enrollment: 20
Study Start Date: October 2007
Study Completion Date: December 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: B
Deferasirox
Drug: deferasirox
20 mg/kg enterally per day
Other Name: Exjade
Drug: Liposomal amphotericin B
Placebo Comparator: A Drug: Placebo Drug: Liposomal amphotericin B

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00419770

Locations
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
UCSF
San Francisco, California, United States, 94143
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Summa Health Systems
Akron, Ohio, United States, 44304
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
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
ClinicalTrials.gov Identifier: NCT00419770     History of Changes
Other Study ID Numbers: 12842
Study First Received: January 5, 2007
Results First Received: June 29, 2011
Last Updated: September 2, 2011
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Mucormycosis
Zygomycosis
Mycoses
Amphotericin B
Deferasirox
Liposomal amphotericin B
Amebicides
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents
Antiparasitic Agents
Antiprotozoal Agents
Chelating Agents
Iron Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Sequestering Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014