Study of Posaconazole Prophylaxis in Patients Receiving Hematopoietic Stem Cell Allograft (Allo-HSC) at High Risk of Invasive Fungal Infection (IFI)
NCT Number: NCT06541067
Acronym: POSALLO
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Hematologic Malignancy
Interventions: DRUG: Posaconazole
Sponsor: Nantes University Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 30
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10-15
Completion Date: 2028-10-15
Locations: CHU Nantes, Nantes, 44000, France

Summary:
Patients receiving an allogeneic hematopoietic stem cell transplant (allo-CSH) are at high risk of infection, particularly of fungal origin. Until the 2018 recommendations of the 6th European Conference on Infections in Leukemia (ECIL6), primary prophylaxis of invasive fungal infections (IFI), in allograft patients, was based on the administration of fluconazole until D100. Due to changes in transplantation practices (alternative donor transplantation, sequential transplantation, etc.) and changes in microbiological ecology (increased incidence of IFIs caused by filamentous germs such as aspergillosis and mycormycosis), fluconazole prophylaxis is now sometimes suboptimal. It is therefore recommended that patients at high risk of developing IFIs should be given azole molecules with activity against filamentous agents as primary prophylaxis during the first 3 months after transplantation.

Posaconazole is often under-dosed (below the minimum effective concentration). It therefore seems essential to carry out a prospective study with close \[C\]min dosing in the specific situation of allograft patients, a population that appears to be at risk of underdosing in the light of initial retrospective analysis results.

Primary Outcome Measures: Effective residual concentration of posaconazole, The main objective is to study, in the early phase after allo-CSH, the percentage of patients who have an effective residual concentration of posaconazole.

The primary endpoint is plasma residual posaconazole concentration (\[C\]min), measured on day 8 of posaconazole initiation. A \[C\]min \> 0.7mg/l is considered effective., On the 8th day of treatment (i.e. after 7 days of treatment)
Secondary Outcome Measures: Monitoring of residual plasma concentrations [C]min, Weekly residual plasma concentrations of posaconazole, From posaconazole baseline up to Day100|Description of circumstances leading to posaconazole underdosing, A clinical record will be taken twice a week during hospitalization and then once a week to describe clinical symptoms leading to malabsorption: nausea, vomiting, diarrhea, mucositis, colitis. Symptom intensity will be assessed according to the NCI CTCAE v5 classification, From posaconazole baseline up to Day100|Description of circumstances leading to posaconazole underdosing, Adherence to treatment will be monitored daily during hospitalization by paramedical staff. Once home, adherence will be assessed once a week by the doctor in charge of the patient, From posaconazole baseline up to Day100|Description of circumstances leading to posaconazole underdosing, All co-medications should be recorded throughout the course of posaconazole treatment, based on data from the patient's medical record, From posaconazole baseline up to Day100|Description of the reasons for administering posaconazole intravenously (IV), The physician in charge of the patient should specify the reason(s) for IV administration of the treatment, From posaconazole baseline up to Day100|Description of situations leading to initial non-administration or early discontinuation of posaconazole, The physician in charge of the patient should specify the situation(s) that led to non-administration or early discontinuation of treatment., From posaconazole baseline up to Day100|Description of situations leading to initial non-administration or early discontinuation of posaconazole, Description of posaconazole-related toxicities according to NCI CTCAE v5 classification, From posaconazole baseline up to Day 100|Description of invasive fungal infections occurring, Description of IFI cases according to EORTC classification, From posaconazole baseline up to 1 year post-transplant and/or through study completion (end of follow-up at the last visit of the last patient included in the study)|Description of patient outcome: incidence of engraftment, Engraftment assessed on hematological reconstitution (number of days of aplasia with PNN \<0.5 G/L and platelets \< 20, number of platelet and packed cell transfusions), Month 1 post-transplant|Description of patient outcome: overall survival (OS), Survival between day 0 of transplantation and date of death or last follow-up, Up to Day100 and 1 year post-transplant and/or through study completion (end of follow-up at the last visit of the last patient included in the study) or death|Description of patient outcome: disease-free survival (DFS), Survival between day 0 of transplant and date of relapse, death or last follow-up, Up to Day100 and 1 year post-transplant and/or through study completion (end of follow-up at the last visit of the last patient included in the study) or documented relapse or death whicvever came first|Description of patient outcome: non-relapse mortality (NRM), Any death unrelated to relapse or disease progression, Up to Day100 and 1 year post-transplant and/or through study completion (end of follow-up at the last visit of the last patient included in the study) or death, whichever came first|Description of patient outcome: incidence of relapse (IR), Any documented disease recurrence, Up to Day100 and 1 year post-transplant and/or through study completion (end of follow-up at the last visit of the last patient included in the study) or any documented disease recurrence, whichever came first|Description of patient outcome: cumulative incidence of acute GVHD, Acute GVH grade 2-4 according to Mount Sinai criteria, Up to Day100 and 1 year post-transplant and/or through study completion (end of follow-up at the last visit of the last patient included in the study)|Description of patient outcome: cumulative incidence of chronic GVHD, Extensive chronic GVH according to NCI criteria, Up to Day100 and 1 year post-transplant and/or through study completion (end of follow-up at the last visit of the last patient included in the study)|Description of patient outcome: GVHD-free relapse-free survival (GRFS), Median relapse-free survival without grade 3-4 acute GVHD or chronic GVHD requiring systemic treatment, Up to Day100 and 1 year post-transplant and/or through study completion (end of follow-up at the last visit of the last patient included in the study) or death|Grade 3 and 4 post-transplant adverse events, Post-transplant grade 3 and 4 adverse events (dates of occurrence) (NCI CTCAE version 5 criteria), Up to Day100 and 1 year post-transplant