MucormycosisPhase 2NCT00419770
The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) Study
A Phase 2 study testing deferasirox and Liposomal amphotericin B in people with Mucormycosis, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 7 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Mucormycosis
- What is being tested?
- deferasirox and Liposomal amphotericin B
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 7 sitesUnited States
- Study dates
- Oct 2007to Dec 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Summa Health Systems
Akron, Ohio, 44304
City of Hope National Medical Center
Duarte, California, 91010
Duke University
Durham, North Carolina, 27710
MD Anderson Cancer Center
Houston, Texas, 77030
University of Miami
Miami, Florida, 33136
UCSF
San Francisco, California, 94143
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
About this study
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
Read the 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.
- Conditions
- Mucormycosis
- Being tested
- deferasirox, Placebo, Liposomal amphotericin B
- Keywords
- zygomycosis, Rhizopus, iron, iron-chelation, adjunctive therapy
- Medical subject headings
- Mucormycosis, Zygomycosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
deferasiroxDrug
Also called Exjade
20 mg/kg enterally per day
PlaceboDrug
Liposomal amphotericin BDrug
| Study group | Role | What they receive |
|---|---|---|
| B | Experimental | Deferasirox Receives: Drug: deferasirox; Drug: Liposomal amphotericin B |
| A | Placebo comparator | Not described Receives: Drug: Placebo; Drug: Liposomal amphotericin B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of Adjunctive Deferasirox Therapy in Patients Being Treated With LAmB for Mucormycosis
Measured: 14 days
Global Response Rate (Composite of Clinical and Radiographic Response) at End of Study Drug Administration, as Determined by a Blinded Adjudication Committee
Measured: 14 days
Total Adverse Events
Measured: 30 Days After End of Therapy
Secondary outcomes (2)
Deferasirox Pharmacokinetic and Pharmacodynamic Parameters
Measured: 7 days
Survival, Radiographic Improvement, Clinical Response, Time to Survival, Deferasirox vs. Free Iron Level Correlation
Measured: Up to 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2007 (estimated)
- Study startOct 2007
- Primary completionDec 2009
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for MucormycosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences, Astellas Pharma Inc, Novartis
- Responsible party
- Sponsor
- Investigators
- Brad Spellberg, MD, Principal investigator, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00419770
- Sponsor's protocol ID
- 12842
- Status last verified
- Oct 2023
- First submitted
- 5 Jan 2007
- Last updated
- 16 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 16020690Ibrahim 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.
PubMed 16928702Reed 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.
PubMed 17000743Boelaert 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.
PubMed 8196268Spellberg 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.
PubMed 21937481
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) Study
- ClinicalTrials.gov ID
- NCT00419770
- Acronym / sponsor ID
- 12842
- Conditions
- Mucormycosis
- Keywords
- zygomycosis, Rhizopus, iron, iron-chelation, adjunctive therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterUniversity, hospital or other
- Collaborators
- Gilead Sciences, Astellas Pharma Inc, Novartis
- Study start
- Oct 2007
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 9 Jan 2007 (estimated)
- Results
- Posted 6 Oct 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| B | Experimental | Drug: deferasirox, Drug: Liposomal amphotericin BDeferasirox |
| A | Placebo comparator | Drug: Placebo, Drug: Liposomal amphotericin B |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| deferasiroxAlso: Exjade20 mg/kg enterally per day | Drug | B |
| Placebo | Drug | A |
| Liposomal amphotericin B | Drug | A, B |
Primary outcome
Safety and Tolerability of Adjunctive Deferasirox Therapy in Patients Being Treated With LAmB for Mucormycosis
Time frame: 14 days
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
Total Adverse Events
Time frame: 30 Days After End of Therapy
2 secondary outcomes
Deferasirox Pharmacokinetic and Pharmacodynamic Parameters
Time frame: 7 days
Survival, Radiographic Improvement, Clinical Response, Time to Survival, Deferasirox vs. Free Iron Level Correlation
Time frame: Up to 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16020690Spellberg 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.
- Background: PubMed 16928702Ibrahim 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.
- Background: PubMed 17000743Reed 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.
- Background: PubMed 8196268Boelaert 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.
- Derived from this study: PubMed 21937481Spellberg 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brad Spellberg, MD principal investigator
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing deferasirox and Liposomal amphotericin B in people with Mucormycosis, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of Adjunctive Deferasirox Therapy in Patients Being Treated With LAmB for Mucormycosis (time frame: 14 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00419770, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2023.