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

NCT ID: NCT00419770

Last Updated: 2023-10-16

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-10-31

Study Completion Date

2010-12-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Mucormycosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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B

Deferasirox

Group Type EXPERIMENTAL

deferasirox

Intervention Type DRUG

20 mg/kg enterally per day

Liposomal amphotericin B

Intervention Type DRUG

A

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Liposomal amphotericin B

Intervention Type DRUG

Interventions

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deferasirox

20 mg/kg enterally per day

Intervention Type DRUG

Placebo

Intervention Type DRUG

Liposomal amphotericin B

Intervention Type DRUG

Other Intervention Names

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Exjade

Eligibility Criteria

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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.
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

Astellas Pharma Inc

INDUSTRY

Sponsor Role collaborator

Novartis

INDUSTRY

Sponsor Role collaborator

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brad Spellberg, MD

Role: PRINCIPAL_INVESTIGATOR

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status

UCSF

San Francisco, California, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Summa Health Systems

Akron, Ohio, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev. 2005 Jul;18(3):556-69. doi: 10.1128/CMR.18.3.556-569.2005.

Reference Type BACKGROUND
PMID: 16020690 (View on PubMed)

Ibrahim AS, Edwards JE Jr, Fu Y, Spellberg B. Deferiprone iron chelation as a novel therapy for experimental mucormycosis. J Antimicrob Chemother. 2006 Nov;58(5):1070-3. doi: 10.1093/jac/dkl350. Epub 2006 Aug 23.

Reference Type BACKGROUND
PMID: 16928702 (View on PubMed)

Reed C, Ibrahim A, Edwards JE Jr, Walot I, Spellberg B. Deferasirox, an iron-chelating agent, as salvage therapy for rhinocerebral mucormycosis. Antimicrob Agents Chemother. 2006 Nov;50(11):3968-9. doi: 10.1128/AAC.01065-06. Epub 2006 Sep 25. No abstract available.

Reference Type BACKGROUND
PMID: 17000743 (View on PubMed)

Boelaert JR, Van Cutsem J, de Locht M, Schneider YJ, Crichton RR. Deferoxamine augments growth and pathogenicity of Rhizopus, while hydroxypyridinone chelators have no effect. Kidney Int. 1994 Mar;45(3):667-71. doi: 10.1038/ki.1994.89.

Reference Type BACKGROUND
PMID: 8196268 (View on PubMed)

Spellberg B, Ibrahim AS, Chin-Hong PV, Kontoyiannis DP, Morris MI, Perfect JR, Fredricks D, Brass EP. The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: a randomized, double-blinded, placebo-controlled trial. J Antimicrob Chemother. 2012 Mar;67(3):715-22. doi: 10.1093/jac/dkr375. Epub 2011 Sep 20.

Reference Type DERIVED
PMID: 21937481 (View on PubMed)

Other Identifiers

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12842

Identifier Type: -

Identifier Source: org_study_id

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