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

NCT00419770 | Completed Phase 2 Results DMC

• 1 other identifier: 12842
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Mucormycosis

Keywords

zygomycosis; Rhizopus; iron; iron-chelation; adjunctive therapy

Outcome Measures

Primary Outcomes (3)

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

  14 days

• Global Response Rate (Composite of Clinical and Radiographic Response) at End of Study Drug Administration, as Determined by a Blinded Adjudication Committee

  14 days

• Total Adverse Events

  30 Days After End of Therapy

Secondary Outcomes (2)

• Deferasirox Pharmacokinetic and Pharmacodynamic Parameters

  7 days

• Survival, Radiographic Improvement, Clinical Response, Time to Survival, Deferasirox vs. Free Iron Level Correlation

  Up to 90 days

Study Arms (2)

B

EXPERIMENTAL

Deferasirox

Drug: deferasirox; Drug: Liposomal amphotericin B

A

PLACEBO COMPARATOR

Drug: Placebo; Drug: Liposomal amphotericin B

Interventions

deferasirox DRUG

20 mg/kg enterally per day

Also known as: Exjade

B

Placebo DRUG

A

Liposomal amphotericin B DRUG

A; B

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: lead
• Gilead Sciences: collaborator
• Astellas Pharma Inc: collaborator
• Novartis: collaborator

Study Sites (7)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

UCSF

San Francisco, California, 94143, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Summa Health Systems

Akron, Ohio, 44304, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (5)

• 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.

  PMID: 16020690 BACKGROUND

• 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.

  PMID: 16928702 BACKGROUND

• 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.

  PMID: 17000743 BACKGROUND

• 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.

  PMID: 8196268 BACKGROUND

• 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.

  PMID: 21937481 DERIVED

MeSH Terms

Conditions

Mucormycosis; Zygomycosis

Interventions

Deferasirox; liposomal amphotericin B

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Brad Spellberg
• Organization: Los Angeles Biomedical Research Institute

bspellberg@dhs.lacounty.gov

310-781-3680

Study Officials

• Brad Spellberg, MD

  Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2007
• First Posted: January 9, 2007
• Study Start: October 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2010
• Last Updated: October 16, 2023
• Results First Posted: October 6, 2011

Record last verified: 2023-10

Locations

US (7)