Study of Posaconazole Prophylaxis in Patients Receiving Hematopoietic Stem Cell Allograft (Allo-HSC) at High Risk of Invasive Fungal Infection (IFI)

NCT ID: NCT06541067

Last Updated: 2026-01-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-08
• Study Completion Date: 2028-11-08

Brief 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.

Detailed Description

There are several treatments based on azole molecules: voriconazole, posaconazole, isavuconazole... To date, none of these treatments has been approved for primary post-allograft prophylaxis. Posaconazole is indicated in cases of graft-versus-host disease (GVHD) (requiring systemic corticosteroid therapy after allo-CSH), and as primary prophylaxis during aplasia in patients with acute myeloblastic leukemia/myelodysplasia (AML/MDS). Other azole molecules are not approved for primary prophylaxis, and may give rise to drug interactions with certain treatments prescribed for allograft patients (e.g. ciclosporin, letermovir).

Although recommendations for the administration of posaconazole as primary prophylaxis post allo-CSH have been in place for 4 years, few studies are available to date. The adult hematology department of Nantes University Hospital conducted a retrospective study of 70 allograft patients at high risk of IFI between 04/2020 and 12/2021. Posaconazole treatment was administered from D0 (or the day after the 2nd dose of post-transplant cyclophosphamide) to D100. Treatment was generally well tolerated, with discontinuation due to possible treatment toxicity in 12.6% of cases, mainly of hepatic origin (n=7). Posaconazole was resumed in 2 cases without recurrence of toxicity. In 84.2% of patients, no IFI was observed. One of the limitations of this study was the low number of determinations of residual posaconazole concentration ([C]min). In fact, [C]min was carried out in only 59 patients/70, with a median delay of 9 days. In 43% of cases, the [C]min was insufficient (< 0.5 mg/L), which is significantly lower than the [C]min obtained in patients with AML/MDS undergoing induction ([C]min< 0.5 mg/L: 5% of patients). It therefore seems essential to carry out a prospective study with close [C]min measurement in the specific situation of allograft patients, a population that appears to be at risk of underdosing in the light of the initial retrospective results of analyses.

Conditions

Hematologic Malignancy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Posaconazole

Group Type: EXPERIMENTAL

Posaconazole

Intervention Type: DRUG

Per Os, on Day 0 of allo-CSH if the patient's condition permits, or after the last dose of immunosuppressor (post-transplant cyclophosphamide) (Day+5 or Day+6 depending on protocols).

On the first day of treatment: 300 mg in the morning (= 3 x 100 mg tablets) and 300 mg in the evening (= 3 x 100 mg tablets), then from day 2 of treatment: 300 mg per day (= 3 x 100 mg tablets) in a single dose

Interventions

Posaconazole

Per Os, on Day 0 of allo-CSH if the patient's condition permits, or after the last dose of immunosuppressor (post-transplant cyclophosphamide) (Day+5 or Day+6 depending on protocols).

On the first day of treatment: 300 mg in the morning (= 3 x 100 mg tablets) and 300 mg in the evening (= 3 x 100 mg tablets), then from day 2 of treatment: 300 mg per day (= 3 x 100 mg tablets) in a single dose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient ≥ 18 years of age. There is no maximum age for inclusion
• Allo-CSH transplant for hematologic malignancy or benign hemopathy of any type with one or more high risk IFI criteria:

• alternative donor (haploidentical intra-family donor, mismatch file donor, placental blood)
• sequential conditioning for disease not in remission at the time of transplantation
• use of post-transplant cyclophosphamide (PTCY) for GVH prophylaxis
• patient who has previously received a HSC allograft
• Written informed consent prior to protocol initiation
• ECOG <=2
• Female of childbearing age with negative pregnancy test and on highly effective contraception during treatment and for 12 months after posaconazole discontinuation
• Men of childbearing age with effective contraception during treatment and for 6 months after stopping posaconazole.
• Hepatitis B, C and HIV serologies negative.
• Social security affiliation

Exclusion Criteria

• Patients with a history of IFI, whether active or resolved at the time of allografting
• Patient with known intolerance to posaconazole
• Patients with concomitant treatments FORBIDDING association with posaconazole: ergot alkaloids, CYP3A4 substrates (terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine), HMG-CoA reductase inhibitors (simvastatin, lovastatin and atorvastatin) or any other contraindicated treatment listed in VIDAL
• patients with congenital or acquired QTc prolongation (QTc >470ms)
• Cardiac: systolic ejection fraction < 50% by transthoracic ultrasound or isotopic method (isotopic gamma-angiography)
• Respiratory: DLCOc <40% of theoretical on EFR
• Renal: creatinine clearance < 50 ml/min (assessed using MDRD method)
• Hepatic: transaminases greater than 5 times normal or bilirubin greater than 2 times normal
• Pregnant or breast-feeding women,
• Women or men of childbearing age without effective contraception
• Serious, uncontrolled concomitant infections
• Yellow fever vaccination within the last year
• Patient protected by law (guardianship, curatorship, safeguard of justice)
• Psychological, family, sociological or geographical conditions that may hinder compliance with the study protocol and follow-up schedule
• Patient who does not speak or understand French
• Participation in any other therapeutic study with an exclusion period still in effect at the time of inclusion or planned participation in another therapeutic study while taking posaconazole

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU Nantes

Nantes, France, France

Site Status: RECRUITING

Countries

France

Central Contacts

Amandine LE BOURGEOIS, MD

Role: CONTACT

amandine.lebourgeois@chu-nantes.fr

02 40 08 32 71 ext. +33

Facility Contacts

Amandine LE BOURGEOIS, MD

Role: primary

amandine.lebourgeois@chu-nantes.fr

02 40 08 32 71 ext. +33

Other Identifiers

RC23_0186

Identifier Type: -

Identifier Source: org_study_id