Empirical Versus Preemptive Antifungal Therapy
- Conditions
- Fungal InfectionLeukemiaMyelodysplastic Syndromes
- Interventions
- Registration Number
- NCT01288378
- Brief 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. 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 556
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Empirical caspofungin acetate Empirical approach (fever driven) for starting antifungal therapy Pre-emptive caspofungin acetate Pre-emptive approach (diagnostic driven) for starting antifungal therapy
- Primary Outcome Measures
Name Time Method Overall survival at 42 days after randomization 6 weeks after randomization
- Secondary Outcome Measures
Name Time Method Safety (adverse event [AE] and serious adverse event [SAE]) as assessed by CTCAE criteria v4.0 during 84 days after randomization Costs related to the strategy for initiating and monitoring antifungal treatment during the 42 and 84 days following randomization during 84 days after randomization Development of proven or probable invasive fungal disease (IFD) during the 42 and 84 days following randomization during 84 days after randomization Overall survival at 84 days after randomization 12 weeks after randomization Survival-free of fungal infection during the 42 and 84 days following randomization 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) at day 42 and day 84 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 during 84 days after randomization
Trial Locations
- Locations (16)
U.Z. Gasthuisberg
🇧🇪Leuven, Belgium
C.H.U. Sart-Tilman
🇧🇪Liège, Belgium
Hopital Universitaire Hautepierre
🇫🇷Strasbourg, France
Institut Gustave Roussy
🇫🇷Villejuif, France
CHU de Caen - Hopital Cote de Nacre
🇫🇷Caen, France
C.H.U. Henri Mondor AP-HP
🇫🇷Créteil, France
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Universitaetsklinikum Wuerzburg - Medizinische Klinik und Poliklinik II
🇩🇪Wuerzburg, Germany
Masaryk University
🇨🇿Brno, Czechia
CHU de Limoges - Hopital Dupuytren
🇫🇷Limoges, France
CHRU de Lille - Hopital Hurie
🇫🇷Lille, France
Radboud University Nijmegen Medical Centre
🇳🇱Nijmegen, Netherlands
National Cancer Institute
🇸🇰Bratislava, Slovakia
A.Z. St. Jan
🇧🇪Brugge, Belgium
Hôpitaux Universitaires Bordet-Erasme - Institut Jules Bordet
🇧🇪Brussels, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium