Targeted antifungal prevention for patients with acute myeloid leukemia

PTX3 Genetically Stratified Randomized Double-blinded Allocation Event-driven Clinical Trial for Antifungal Prophylaxis in Patients With Acute Myeloid Leukemia

This study is testing if a specific antifungal treatment can help patients with acute myeloid leukemia who are getting chemotherapy avoid serious infections.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 410 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre Hospitalier Universitaire Vaudois (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 9 sites (Ghent, Belgium and 8 other locations)
• Trial ID: NCT03828773 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of posaconazole-based antifungal prophylaxis strategies in patients with acute myeloid leukemia (AML) undergoing chemotherapy. It employs a genetically-stratified, randomized, double-blind design to allocate treatment based on the risk of invasive mold infections. The study aims to optimize antifungal use by identifying high-risk patients who would benefit most from broad-spectrum antifungal treatment. The trial is conducted across multiple centers to gather diverse data on patient outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older diagnosed with acute myeloid leukemia or myelodysplastic syndrome undergoing intensive chemotherapy.

Not a fit: Patients with acute promyelocytic leukemia, those already experiencing neutropenia, or individuals with a history of severe reactions to azole antifungals may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the incidence of invasive mold infections in high-risk AML patients, improving their overall survival rates.

How similar studies have performed: Previous studies have shown promise in using targeted antifungal prophylaxis in similar patient populations, indicating potential for success in this approach.

Eligibility criteria

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)

Where this trial is running

Ghent, Belgium and 8 other locations

• Ghent University Hospital — Ghent, Belgium, 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, France (Recruiting)
• Cantonal Hospital Aarau — Aarau, Aarau, Switzerland (Recruiting)
• University Hospital Basel — Basel, Basel, Switzerland (Recruiting)
• Cantonal Hospital HFR — Fribourg, Canton of Fribourg, Switzerland (Recruiting)
• University Hospital of Geneva (HUG) — Geneva, Canton of Geneva, Switzerland (Recruiting)
• University Hospital of Lausanne / Centre Hospitalier Universitaire Vaudois (CHUV) — Lausanne, Canton of Vaud, Switzerland (Recruiting)

Study contacts

• Principal investigator: Pierre-Yves Bochud, MD — Centre Hospitalier Universitaire Vaudois
• Study coordinator: Pierre-Yves Bochud, MD

Conditions Candidiasis; Fungal Infection; Acute Myeloid Leukemia; Genetic Predisposition; Aspergillosis