Posaconazole: Posaconazole is a triazole with broad-spectrum activity, to include Candida species, Aspergillus species, and other fungal pathogens, including the Zygomycetes. Posaconazole is available as slow release tablets (300mg/day) and as intravenous (IV) formulation (300mg/day) and is licensed and approved in Switzerland for the prevention of IFI, including mold and yeast infections, in patients \>18 years who are at high risk of developing these types of infection (patients with long-term neutropenia or HCT recipients). Furthermore, international guidelines recommend posaconazole for primary antifungal prophylaxis in high-risk patients, such as AML patients with prolonged neutropenia. Posaconazole is available in Switzerland under the name of Noxafil® in capsules of 100mg, suspension of 40mg/mL and intravenous formulation of 300mg/16.7 mL.
Fluconazole: Fluconazole is an antifungal with activity against most Candida species. Fluconazole is licensed and approved in Switzerland for prophylaxis of IC in patients with neutropenia induced by chemotherapy or radiotherapy at a daily dose of 200 to 400 mg once daily. Fluconazole (200 mg or 400 mg once daily) is still currently used as primary antifungal prophylaxis (standard of care) in all 7 centers participating in this trial. Fluconazole is available in Switzerland under the name of Diflucan® in capsules of 50 mg, 150 mg and 200 mg and in powder for preparation of suspension (50 mg/5 ml and 200 mg/5 ml (forte)) or perfusion (2 mg/1 ml). Several generics of Diflucan® are authorized in Switzerland. Prescribing Diflucan® or any of its generics will remain at the discretion of and based on the standard operating procedures (SOP) at each institution.
Study summary
This is a prospective genetically-stratified randomized double-blind event-driven multicentre clinical trial to assess the efficacy of posaconazole-based antifungal prophylaxis allocation strategies for patients with acute myeloid leukemia who receive induction chemotherapy. Allocation strategy based on an invasive mold infection genetic risk will be double-blinded.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Signed Informed Consent according to national/local regulations.
2. Age ≥18 years.
3. Diagnosis of Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome in transformation (MDSit) treated with an intensive chemotherapy regimen, including induction / consolidation / salvage remission chemotherapy.
4. Planned hospital admission for the duration of the neutropenic phase (absolute neutrophils count \<500 cells/mm3).
Exclusion Criteria:
1. Patients with neutropenia (absolute neutrophils count\<500 cells/mm3) upon presentation and prior to chemotherapy initiation.
2. Patients with a diagnosis of acute promyelocytic leukemia (APL) or AML-M3.
3. Patients with known history of allergy, hypersensitivity or serious reaction to azole antifungals
4. Women who are pregnant (positive blood/urine pregnancy test within 10 days before randomization) or breast-feeding.
5. Diagnosis and treatment for an Invasive Fungal Infection (IFI) within 3 months prior to study enrolment and an Invasive Mold Infection (IMI) at any point prior to or at the time of enrolment.
6. Severe liver dysfunction, defined as at least one of the following markers: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) or alkaline phosphatase above \>5x upper limit of normality: and/or total bilirubin above \>3x upper limit of normality.
7. Patients with an ECG with a prolonged QTc interval: QTc greater than 450 msec for men and greater than 470 msec for women.
8. Patients who are receiving and cannot discontinue the following drugs at least 24 hours prior to randomization: terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine (because of the possibility of QT prolongation), sirolimus, rifampin, rifabutin, carbamazepine, long-acting barbiturates (e.g., phenobarbital, mephobarbital), ritonavir, efavirenz, or ergot alkaloids (e.g., ergotamine, dihydroergotamine).
9. Serious uncontrolled concomitant disease or comorbidity that, in the opinion of the investigator, may compromise adherence to the study protocol.
10. Receipt of a prior allogeneic Hematopoietic Cell Transplantation (HCT).
11. Previous exposure to mold-active prophylaxis (\>48 hours within 7 days of inclusion).
12. Patients with relapsed leukemia already included in the trial.
13. Patient not affiliated to the French social security system
14. Patient under legal protection (guardianship, curatorship)
Primary outcome measure(s)
Cumulative incidence of proven and probable invasive mold infection (IMI) — Day 180 The cumulative incidence of proven and probable invasive mold infection (IMI) (based on published consensus guidelines by the EORTC/MSG groups and after validation by an independent adjudication committee of infectious disease experts blinded to treatment arms) in the intention-to-treat (ITT) population by day 180.
Trial sites (9)
Facility
City
Region
Status
Ghent University Hospital
Ghent
Belgium
Terminated
AZ Sint-Jan Hospital
Bruges
Belgium
Recruiting
University Hospital Leuven (UZ Leuven)
Leuven
Belgium
Recruiting
Henri Mondor Hospital
Créteil
Île-de-France Region
Recruiting
Cantonal Hospital Aarau
Aarau
Aarau
Recruiting
University Hospital Basel
Basel
Basel
Recruiting
Cantonal Hospital HFR
Fribourg
Canton of Fribourg
Recruiting
University Hospital of Geneva (HUG)
Geneva
Canton of Geneva
Recruiting
University Hospital of Lausanne / Centre Hospitalier Universitaire Vaudois (CHUV)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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