Posaconazole for Acute myeloid leukemia | Myelodysplastic syndromes

Stratification factors

• Genetic risk strata based on PTX3 genotype (high-risk vs low-risk)

Inclusion criteria

• {"criterion_text":"- Signed informed consent according to national/local regulations\n- Age ≥18 years\n- Diagnosis of AML or MDSit (de novo or secondary) treated with an intensive chemotherapy regimen, including induction / consolidation / salvage chemotherapy\n- Planned hospital admission for the duration of the neutropenic phase (ANC<500 cells/mm3)"}

Exclusion criteria

• {"criterion_text":"- Patients with neutropenia (ANC<500 cells/mm3) at hospital admission (first inpatient blood analysis)\n- Receipt of a prior allogeneic HCT\n- Previous exposure to mold-active prophylaxis (>48 hours within 7 days of inclusion).\n- Patients with relapsed leukemia already included in the trial\n- Patients with a diagnosis of acute promyelocytic leukemia (APL) or AML-M3\n- Patients with known history of allergy, hypersensitivity or serious reaction to azole antifungals\n- Women who are pregnant (positive blood/urine pregnancy test within 10 days before randomization) or breast feeding\n- Diagnosis and treatment for an IFI within 3 months prior to study enrolment and an IMI at any point prior to or at the time of enrolment\n- Severe liver dysfunction, defined as at least one of the following markers: AST, ALT, alkaline phosphatase, and/or total bilirubin above >5x upper limit of normality documented on the first inpatient analysis if still present at inclusion and considered contra-indicated by the clinical team\n- Patients with a prolonged QTc interval on at least 2 electrocardiograms (ECG): QTc greater than 450 msec for men and greater than 470 msec for women, and if considered contra-indicated by the clinical team\n- 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)\n- Serious uncontrolled concomitant disease or comorbidity that, in the opinion of the investigator, may compromise adherence to the study protocol"}

Primary endpoints

• {"endpoint_text":"- The cumulative incidence of proven and probable invasive fungal infections, invasive mold infections and invasive aspergillosis (IMI) at 180 days is defined as the proportion of patients who experienced proven and probable IMI within 180 days from the first dose of antifungal prophylaxis treatment after randomization.","definition_or_measurement_approach":"Defined as the proportion of patients who experienced proven and probable IMI within 180 days from the first dose of antifungal prophylaxis after randomization; time window days 0-180."}

Secondary endpoints

• {"endpoint_text":"- The cumulative incidence of possible IMI by day 180 in the ITT population.","definition_or_measurement_approach":"Cumulative incidence of possible invasive mold infection by day 180 in the intent-to-treat population."}
• {"endpoint_text":"- The cumulative incidence of probable and proven IFI, namely: (a) all IFI, (b) IA only and (c) IC only in the ITT patient population by day 180","definition_or_measurement_approach":"Cumulative incidence by day 180 in the ITT population for (a) all invasive fungal infections, (b) invasive aspergillosis only, (c) invasive candidiasis only."}
• {"endpoint_text":"- The time to probable and proven IMI during 180 days in the ITT population.","definition_or_measurement_approach":"Time-to-event (time to probable/proven IMI) within 180 days in ITT population."}
• {"endpoint_text":"- The overall survival in the ITT population by day 180.","definition_or_measurement_approach":"Overall survival status assessed by day 180 in the ITT population."}
• {"endpoint_text":"- The time to first use and the number of patient-days of amphotericin B or an echinocandin in the ITT population during 180 days.","definition_or_measurement_approach":"Time to first administration and aggregate patient-days of amphotericin B or an echinocandin within 180 days in ITT population."}
• {"endpoint_text":"- The frequency and distribution of adverse events (AE) of interest in posaconazole and fluconazole treated participants in the ITT population during 180 days, namely (a) elevation of liver tests and (b) prolongation of QTc interval on ECG.","definition_or_measurement_approach":"AE frequency and distribution over 180 days in ITT for specified AEs: liver test elevations and QTc prolongation on ECG."}
• {"endpoint_text":"- The cumulative incidence of probable and proven IFI, namely: all IFI, all IMI, IA only and IC only in the per protocol (PP) population by day 180.","definition_or_measurement_approach":"Cumulative incidence by day 180 in the per-protocol population for listed IFI categories."}

Belgium

Earliest CTIS Part Ii Submission Date

14-10-2024

Latest Decision Or Authorization Date

16-10-2024

Processing Time Days

2

Number Of Sites

3

Number Of Participants

105

France

Earliest CTIS Part Ii Submission Date

14-10-2024

Latest Decision Or Authorization Date

17-10-2024

Processing Time Days

3

Number Of Sites

1

Number Of Participants

48

Primary sponsor

Full Name

Centre Hospitalier Universitaire Vaudois

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Switzerland