Fungal InfectionPhase 3NCT01288378
Empirical Versus Preemptive Antifungal Therapy
A Phase 3 study testing caspofungin acetate in people with Fungal Infection and Leukemia, run by European Organisation for Research and Treatment of Cancer - EORTC at 16 sites in 6 countries.
Trial summary
RATIONALE: Caspofungin acetate may be effective in treating fungal infections in patients with acute myeloid leukemia or myelodysplastic syndrome who are receiving treatment for their cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fungal Infection, Leukemia, Myelodysplastic Syndromes
- What is being tested?
- caspofungin acetate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 556 participants
- Where
- 16 sitesin 6 countries
- Study dates
- Mar 2012to 4 Apr 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
- Newly diagnosed disease or disease in first relapse after hematological remission lasting for a minimum of 6 months AND meets one of the following criteria:
- Starting remission-induction chemotherapy within 3 days prior to study randomization
- Starting myeloablative conditioning regimen to prepare for a first allogeneic hematopoietic stem cell transplantation within 3 days prior to study randomization
- Planning a hospital admission for the duration of the neutropenic phase (ANC < 0.5 x 10^9 /L)
- Planning to receive oral or intravenous fluconazole for Candida prophylaxis at a dose of 400 mg/day
- Fluconazole is discontinued during caspofungin acetate administration
- No previous or current history of proven or probable invasive fungal disease (IFD)
PATIENT CHARACTERISTICS:
- See Disease Characteristics
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients muse use effective contraception during and for at least 3 months after completion of study therapy
- No current clinical diagnosis of pneumonia
- No serious, uncontrolled, concomitant disease or comorbidity that, in the opinion of the investigator, may compromise adherence to the study protocol
- No history of allergy or any adverse reaction to echinocandin drugs (i.e., caspofungin acetate, micafungin, or anidulafungin)
- No hypersensitivity to caspofungin active substance or to any of the excipients
- No inadequately treated infection
- No documented HIV infection
- No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- No history of liver cirrhosis or severe hepatic insufficiency (i.e., Child Pugh Class C, D, or E)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No concurrent participation on another clinical trial using an investigational drug for infectious diseases
- No other concurrent systemic antifungal therapy (oral or intravenous)
Trial locations and contacts
16 sites in 6 countries.
16 sites in 6 countries
France6 sites
CHU de Caen - Hopital Cote de Nacre
Caen
C.H.U. Henri Mondor AP-HP
Créteil
CHRU de Lille - Hopital Hurie
Lille
CHU de Limoges - Hopital Dupuytren
Limoges
Hopital Universitaire Hautepierre
Strasbourg
Institut Gustave Roussy
Villejuif
Belgium5 sites
A.Z. St. Jan
Bruges
Cliniques Universitaires Saint-Luc
Brussels
Hôpitaux Universitaires Bordet-Erasme - Institut Jules Bordet
Brussels
U.Z. Gasthuisberg
Leuven
C.H.U. Sart-Tilman
Liège
Germany2 sites
Universitaetsklinikum Freiburg
Freiburg im Breisgau
Universitaetsklinikum Wuerzburg - Medizinische Klinik und Poliklinik II
Würzburg
About this study
Official title: Empirical Versus Pre-emptive (Diagnostic-driven) Antifungal Therapy of Patients Treated for Haematological Malignancies or Receiving an Allogeneic Stem Cell Transplant. A Therapeutic Open Label Phase III Strategy Study of the EORTC Infectious Diseases and Leukemia Groups
RATIONALE: Caspofungin acetate may be effective in treating fungal infections in patients with acute myeloid leukemia or myelodysplastic syndrome who are receiving treatment for their cancer. It is not yet known whether caspofungin acetate is more effective when treatment starts after development of a fever or after the infection is shown in laboratory test, chest x-ray, or CT scan.
PURPOSE: This randomized phase III trial is studying the best time to start caspofungin acetate therapy in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly diagnosed or in first relapse.
Read the detailed description
OBJECTIVES:
Primary
- To compare empirical approach (i.e., fever driven) versus preemptive approach (i.e., diagnostic driven), for starting antifungal therapy with caspofungin acetate, in patients with acute myeloid leukemia or myelodysplastic syndrome who are starting chemotherapy (for attaining remission induction) or myeloablation (to prepare for an allogeneic hematopoietic stem cell transplantation) for newly diagnosed disease or disease in first relapse.
Secondary
- To evaluate clinical validity and utility of a standardized Aspergillus PCR assay.
- To evaluate clinical validity and utility of beta-D-glucan.
- To determine the occurrence of single nucleotide polymorphisms (SNPs) and the predictive value of SNPs for identifying patients at higher risk of developing invasive fungal infection.
OUTLINE: This is a multicenter study. Patients are stratified according to institution, prior allogeneic stem cell transplantation (yes vs no), and type of air flow (laminar air flow vs high-efficiency particulate air). Patients are randomized to 1 of 2 treatment arms.
- Arm A (Empirical approach): Patients start caspofungin acetate treatment when one of the following criteria are met:
- Presence of unexplained persistent fever refractory to 4 full days of broad-spectrum antibacterial therapy with any of the following regimens either alone or in combination with an aminoglycoside or a glycopeptide:
- Ceftazidime
- Cefepime
- Piperacillin/tazobactam
- Imipenem-cilastatin
- Meropenem
- New fever occurring > 2 days after resolution of a first fever while continuing broad-spectrum antibacterial therapy as defined above for which no obvious cause has been documented and fungal infection cannot be excluded Patients receive caspofungin acetate IV once daily. Treatment continues until neutrophil recovers.
- Arm B (Preemptive approach): Patients start caspofungin acetate treatment when at least one of the following criteria* are met:
- Single plasma or serum galactomannan ELISA with index > 0.5
- New pulmonary infiltrate on chest x-ray and IFD cannot be readily excluded
- New dense well-circumscribed lesions with or without a halo sign, on a CT scan, consistent with IFD
- Aspergillus sp. recovered by culture from sputum Patients receive caspofungin acetate IV once daily. Treatment continues until neutrophil recovers.
NOTE: *These criteria are not sufficient to warrant preemptive caspofungin acetate therapy: skin lesions evocative of IFD, sinusitis or orbititis, hepatosplenic abscesses (hypodensities on CT scan), or unexplained persistent fever for more than 7 days or recurrent fever whatever its duration.
All patients undergo blood sample collection periodically for the detection of galactomannan and beta-D-glucan and for the detection of single nucleotide polymorphisms. Some patients undergo blood sample collection for the detection of Aspergillus via PCR. An economic evaluation is performed for cost-effectiveness analysis.
After completion of study treatment, patients are followed periodically.
- Conditions
- Fungal Infection, Leukemia, Myelodysplastic Syndromes
- Being tested
- caspofungin acetate
- Keywords
- fungal infection, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, recurrent adult acute myeloid leukemia, untreated adult acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with del(5q), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), secondary acute myeloid leukemia
- Medical subject headings
- Mycoses, Leukemia, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
caspofungin acetateDrug
intravenous route, at a 70 mg loading dose on day 1 of antifungal therapy, followed by 50 mg once a day thereafter.
| Study group | Role | What they receive |
|---|---|---|
| Empirical | Active comparator | Empirical approach (fever driven) for starting antifungal therapy Receives: Drug: caspofungin acetate |
| Pre-emptive | Experimental | Pre-emptive approach (diagnostic driven) for starting antifungal therapy Receives: Drug: caspofungin acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival at 42 days after randomization
Measured: 6 weeks after randomization
Secondary outcomes (7)
Overall survival at 84 days after randomization
Measured: 12 weeks after randomization
Development of proven or probable invasive fungal disease (IFD) during the 42 and 84 days following randomization
Measured: during 84 days after randomization
Proper management according to allocated treatment arm (i.e., appropriate administration of caspofungin acetate in compliance to protocol, and compliance to the treatment strategy) during the 42 and 84 days after randomization
Measured: during 84 days after randomization
Survival-free of fungal infection during the 42 and 84 days following randomization
Measured: during 84 days after randomization
Safety (adverse event [AE] and serious adverse event [SAE]) as assessed by CTCAE criteria v4.0
Measured: during 84 days after randomization
Number of days under caspofungin treatment or under another antifungal treatment administered after caspofungin (evaluation will be done at day 42 and day 84 after randomization)
Measured: at day 42 and day 84 after randomization
Costs related to the strategy for initiating and monitoring antifungal treatment during the 42 and 84 days following randomization
Measured: during 84 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2011 (estimated)
- Study startMar 2012
- Primary completion4 Apr 2019
- Study completion4 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fungal InfectionStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 556 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01288378
- Sponsor's protocol ID
- EORTC-65091-06093
- Other IDs
- 2010-020814-27, MK-0991-070
- Status last verified
- Dec 2023
- First submitted
- 1 Feb 2011
- Last updated
- 11 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Maertens J, Lodewyck T, Donnelly JP, Chantepie S, Robin C, Blijlevens N, Turlure P, Selleslag D, Baron F, Aoun M, Heinz WJ, Bertz H, Racil Z, Vandercam B, Drgona L, Coiteux V, Llorente CC, Schaefer-Prokop C, Paesmans M, Ameye L, Meert L, Cheung KJ, Hepler DA, Loeffler J, Barnes R, Marchetti O, Verweij P, Lamoth F, Bochud PY, Schwarzinger M, Cordonnier C; Infectious Diseases Group and the Acute Leukemia Group of the European Organization for Research and Treatment of Cancer. Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer. Clin Infect Dis. 2023 Feb 18;76(4):674-682. doi: 10.1093/cid/ciac623.
PubMed 35906831
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Empirical Versus Pre-emptive (Diagnostic-driven) Antifungal Therapy of Patients Treated for Haematological Malignancies or Receiving an Allogeneic Stem Cell Transplant. A Therapeutic Open Label Phase III Strategy Study of the EORTC Infectious Diseases and Leukemia Groups
- ClinicalTrials.gov ID
- NCT01288378
- Acronym / sponsor ID
- EORTC-65091-06093
- Conditions
- Fungal Infection, Leukemia, Myelodysplastic Syndromes
- Keywords
- fungal infection, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, recurrent adult acute myeloid leukemia, untreated adult acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with del(5q)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 556 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Study start
- Mar 2012
- Primary completion
- 4 Apr 2019 (actual)
- Study completion
- 4 Apr 2019 (actual)
- First posted
- 2 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Caspofungin acetate may be effective in treating fungal infections in patients with acute myeloid leukemia or myelodysplastic syndrome who are receiving treatment for their cancer. It is not yet known whether caspofungin acetate is more effective when treatment starts after development of a fever or after the infection is shown in laboratory test, chest x-ray, or CT scan.
PURPOSE: This randomized phase III trial is studying the best time to start caspofungin acetate therapy in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly diagnosed or in first relapse.
Detailed description
OBJECTIVES:
Primary
- To compare empirical approach (i.e., fever driven) versus preemptive approach (i.e., diagnostic driven), for starting antifungal therapy with caspofungin acetate, in patients with acute myeloid leukemia or myelodysplastic syndrome who are starting chemotherapy (for attaining remission induction) or myeloablation (to prepare for an allogeneic hematopoietic stem cell transplantation) for newly diagnosed disease or disease in first relapse.
Secondary
- To evaluate clinical validity and utility of a standardized Aspergillus PCR assay.
- To evaluate clinical validity and utility of beta-D-glucan.
- To determine the occurrence of single nucleotide polymorphisms (SNPs) and the predictive value of SNPs for identifying patients at higher risk of developing invasive fungal infection.
OUTLINE: This is a multicenter study. Patients are stratified according to institution, prior allogeneic stem cell transplantation (yes vs no), and type of air flow (laminar air flow vs high-efficiency particulate air). Patients are randomized to 1 of 2 treatment arms.
- Arm A (Empirical approach): Patients start caspofungin acetate treatment when one of the following criteria are met:
- Presence of unexplained persistent fever refractory to 4 full days of broad-spectrum antibacterial therapy with any of the following regimens either alone or in combination with an aminoglycoside or a glycopeptide:
- Ceftazidime
- Cefepime
- Piperacillin/tazobactam
- Imipenem-cilastatin
- Meropenem
- New fever occurring > 2 days after resolution of a first fever while continuing broad-spectrum antibacterial therapy as defined above for which no obvious cause has been documented and fungal infection cannot be excluded Patients receive caspofungin acetate IV once daily. Treatment continues until neutrophil recovers.
- Arm B (Preemptive approach): Patients start caspofungin acetate treatment when at least one of the following criteria* are met:
- Single plasma or serum galactomannan ELISA with index > 0.5
- New pulmonary infiltrate on chest x-ray and IFD cannot be readily excluded
- New dense well-circumscribed lesions with or without a halo sign, on a CT scan, consistent with IFD
- Aspergillus sp. recovered by culture from sputum Patients receive caspofungin acetate IV once daily. Treatment continues until neutrophil recovers.
NOTE: *These criteria are not sufficient to warrant preemptive caspofungin acetate therapy: skin lesions evocative of IFD, sinusitis or orbititis, hepatosplenic abscesses (hypodensities on CT scan), or unexplained persistent fever for more than 7 days or recurrent fever whatever its duration.
All patients undergo blood sample collection periodically for the detection of galactomannan and beta-D-glucan and for the detection of single nucleotide polymorphisms. Some patients undergo blood sample collection for the detection of Aspergillus via PCR. An economic evaluation is performed for cost-effectiveness analysis.
After completion of study treatment, patients are followed periodically.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empirical | Active comparator | Drug: caspofungin acetateEmpirical approach (fever driven) for starting antifungal therapy |
| Pre-emptive | Experimental | Drug: caspofungin acetatePre-emptive approach (diagnostic driven) for starting antifungal therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| caspofungin acetateintravenous route, at a 70 mg loading dose on day 1 of antifungal therapy, followed by 50 mg once a day thereafter. | Drug | Empirical, Pre-emptive |
Primary outcome
Overall survival at 42 days after randomization
Time frame: 6 weeks after randomization
7 secondary outcomes
Overall survival at 84 days after randomization
Time frame: 12 weeks after randomization
Development of proven or probable invasive fungal disease (IFD) during the 42 and 84 days following randomization
Time frame: during 84 days after randomization
Proper management according to allocated treatment arm (i.e., appropriate administration of caspofungin acetate in compliance to protocol, and compliance to the treatment strategy) during the 42 and 84 days after randomization
Time frame: during 84 days after randomization
Survival-free of fungal infection during the 42 and 84 days following randomization
Time frame: during 84 days after randomization
Safety (adverse event [AE] and serious adverse event [SAE]) as assessed by CTCAE criteria v4.0
Time frame: during 84 days after randomization
Number of days under caspofungin treatment or under another antifungal treatment administered after caspofungin (evaluation will be done at day 42 and day 84 after randomization)
Time frame: at day 42 and day 84 after randomization
Costs related to the strategy for initiating and monitoring antifungal treatment during the 42 and 84 days following randomization
Time frame: during 84 days after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2023.
- Derived from this study: PubMed 35906831Maertens J, Lodewyck T, Donnelly JP, Chantepie S, Robin C, Blijlevens N, Turlure P, Selleslag D, Baron F, Aoun M, Heinz WJ, Bertz H, Racil Z, Vandercam B, Drgona L, Coiteux V, Llorente CC, Schaefer-Prokop C, Paesmans M, Ameye L, Meert L, Cheung KJ, Hepler DA, Loeffler J, Barnes R, Marchetti O, Verweij P, Lamoth F, Bochud PY, Schwarzinger M, Cordonnier C; Infectious Diseases Group and the Acute Leukemia Group of the European Organization for Research and Treatment of Cancer. Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer. Clin Infect Dis. 2023 Feb 18;76(4):674-682. doi: 10.1093/cid/ciac623.
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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.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing caspofungin acetate in people with Fungal Infection and Leukemia, run by European Organisation for Research and Treatment of Cancer - EORTC at 16 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 11 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in France, Belgium, Germany, Czechia, Netherlands and 1 more country. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Overall survival at 42 days after randomization (time frame: 6 weeks after randomization). 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 NCT01288378, which also lists 1 linked publication.
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 11 Dec 2023.