Acute Myeloid Leukemia Clinical Trial
— PTX3AMLOfficial title:
PTX3 Genetically Stratified Randomized Double-blinded Allocation Event-driven Clinical Trial for Antifungal Prophylaxis in Patients With Acute Myeloid Leukemia
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.
Status | Recruiting |
Enrollment | 320 |
Est. completion date | November 30, 2025 |
Est. primary completion date | November 30, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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). |
Country | Name | City | State |
---|---|---|---|
Belgium | AZ Sint-Jan Hospital | Bruges | |
Belgium | Ghent University Hospital | Ghent | |
Belgium | University Hospital Leuven (UZ Leuven) | Leuven | |
France | Henri Mondor Hospital | Créteil | Ile De France |
Switzerland | Cantonal Hospital Aarau | Aarau | |
Switzerland | University Hospital Basel | Basel | |
Switzerland | Cantonal Hospital HFR | Fribourg | |
Switzerland | University Hospital of Geneva (HUG) | Geneva | |
Switzerland | University Hospital of Lausanne / Centre Hospitalier Universitaire Vaudois (CHUV) | Lausanne | Vaud |
Lead Sponsor | Collaborator |
---|---|
Bochud Pierre-Yves | Swiss National Science Foundation |
Belgium, France, Switzerland,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Cumulative incidence of proven and probable invasive mold infection (IMI) | 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. | Day 180 | |
Secondary | Cumulative incidence of possible invasive mold infection (IMI) | The cumulative incidence of possible 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) by day 180 in the ITT population. | Day 180 | |
Secondary | Cumulative incidence of probable and proven Invasive Fungal Infections (IFI) | The cumulative incidence of probable and proven Invasive Fungal Infections (IFI) (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), namely: (a) all IFI, (b) Invasive Aspergillosis (IA) only and (c) Invasive Candidiasis (IC) only in the ITT patient population by day 180. | Day 180 | |
Secondary | Time to probable and proven invasive mold infection (IMI) | The time to probable and proven 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) during 180 days in the ITT population | Day 180 | |
Secondary | Cumulative incidence of mortality | The cumulative incidence of mortality in the ITT population by day 180. | Day 180 | |
Secondary | Time to use of amphotericin B/echinocandin | The time to use of amphotericin B/echinocandin in the ITT population during 180 days. | Day 180 | |
Secondary | Number of patient-days of amphotericin B/echinocandin | The number of patient-days of amphotericin B/echinocandin in the ITT population during 180 days. | Day 180 | |
Secondary | Frequency/distribution of adverse events (AE) of interest | The frequency/distribution of AE of interest in posaconazole and fluconazole treated participants in the ITT population during 180 days, namely:
Hepatotoxicity, defined by elevation of at least one of the following markers above >5x upper limit of normal: transaminases, alkaline phosphatase and/or above >3x upper limit of normal total bilirubin New QTc prolongation, defined as QTc >450 msec for men and >470 msec for women |
Day 180 | |
Secondary | Cumulative incidence of probable and proven invasive fungal infections (IFI) in per protocol population | The cumulative incidence of probable and proven invasive fungal infections (IFI) (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) , namely: all Invasive Fungal Infections (IFI), all Invasive Mold Infections (IMI), Invasive Aspergillosis (IA) only and Invasive Candidiasis (IC) only in the per protocol (PP) population by day 180. | Day 180 |
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