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Clinical Trial Results:
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

Summary
EudraCT number	2010-020814-27
Trial protocol	DE NL BE CZ SK
Global end of trial date	04 Apr 2019

Results information
Results version number	v1(current)
This version publication date	12 Feb 2021
First version publication date	12 Feb 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
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Trial information

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Sponsor protocol code

65091-06093

ISRCTN number

US NCT number

NCT01288378

WHO universal trial number (UTN)

Sponsor organisation name

European Organisation for Research and Treatment of Cancer

Sponsor organisation address

Avenue E Mounier 83/11, Brussels, Belgium, 1200

Public contact

Regulatory Affairs Department, European Organisation for Research and Treatment of Cancer, 32 27741611, regulatory@eortc.org

Scientific contact

Regulatory Affairs Department, European Organisation for Research and Treatment of Cancer, 32 27741611, regulatory@eortc.org

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

23 Dec 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

23 Dec 2015

Global end of trial reached?

Yes

Global end of trial date

04 Apr 2019

Was the trial ended prematurely?

Main objective of the trial

The main objective of the trial is to compare two strategies, namely an empirical approach (fever driven) (EAT, arm A) versus pre-emptive (diagnostic driven) (PAT, Arm B) approach, for starting antifungal therapy (with caspofungin) for managing patients treated with chemotherapy for attaining remission induction of acute myeloid leukemia or myelodysplastic syndrome or myeloablation to prepare for an allogeneic HSCT, by assessing the survival rates 42 days (6 weeks) after initial randomization. The intent is to show the non-inferiority of the pre-emptive approach.

Protection of trial subjects

The responsible investigator ensures that this study is conducted in agreement with either the Declaration of Helsinki (available on the World Medical Association web site (http://www.wma.net)) and/or the laws and regulations of the country, whichever provides the greatest protection of the patient. The protocol has been written, and the study conducted according to the ICH Harmonized Tripartite Guideline on Good Clinical Practice (ICH-GCP, available online at http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002874. pdf). The protocol was approved by the competent ethics committee(s) as required by the applicable national legislation.

Background therapy

Patients in this study are treated with chemotherapy for attaining remission induction of acute myeloid leukemia or myelodysplastic syndrome or myeloablation to prepare for an allogeneic HSCT

Evidence for comparator

Early antifungal therapy and clinical awareness of the possibility of an invasive fungal infection remain crucial prerequisites to avoid the confrontation with a stage of infection beyond a reasonable chance of cure. By consequence, treatment is often commenced on an empirical basis, i.e. for fever not responding to adequate antibacterial therapy. The perceived need for systematically active antifungal therapy may vary between 10% and 80% in different centers. This strategy is based on few studies, that are now cited as gold standards but which comprised only a limited number of patients. Nevertheless, after publication of these studies, the empirical use of broad-spectrum antifungals in persistently febrile neutropenic cancer patients has become a more or less generally accepted strategy. Consequently, an increasing number of investigators institute broad-spectrum antifungal for neutropenic patients whose fever persists for 3 or more days. This probably reflects a common attitude particularly in North-America, where two-thirds of the patients in prophylactic studies on fluconazole for acute leukemia and bone marrow transplants received empirical broad-spectrum antifungals to, whereas in a large European study in a similar population only 20% of the patients received empirical intravenous antifungal drugs. Indeed, in Europe, most centers will commence systemic empirical antifungal therapy after 5 days of fever not responding to antibiotics, while others are even more selective being guided by clinical, radiological and microbiological parameters suggestive of an invasive fungal infection. Therefore, the question of the optimal time point to start antifungal treatment remains. It seems warranted to try to establish more rational grounds to initiate antifungal therapy in persistently febrile neutropenic patients. The drug of choice for such a pre-emptive approach remains to be determined, but caspofungin may prove to be a good candidate.

Actual start date of recruitment

09 Mar 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country