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

NCT06541067 | Recruiting Phase 2

• 1 other identifier: RC23_0186
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematologic Malignancy

Keywords

Hematopoietic stem cell allograft (Allo-CSH); Posaconazole; Pharmacology

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (17)

• Monitoring of residual plasma concentrations [C]min

  From posaconazole baseline up to Day100

• Description of circumstances leading to posaconazole underdosing

  From posaconazole baseline up to Day100

• Description of circumstances leading to posaconazole underdosing

  From posaconazole baseline up to Day100

• Description of circumstances leading to posaconazole underdosing

  From posaconazole baseline up to Day100

• Description of the reasons for administering posaconazole intravenously (IV)

  From posaconazole baseline up to Day100

Study Arms (1)

Posaconazole

EXPERIMENTAL

Drug: Posaconazole

Interventions

Posaconazole 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

Posaconazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

CHU Nantes

Nantes, France, 44000, France

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

posaconazole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Amandine LE BOURGEOIS, MD

CONTACT

02 40 08 32 71; amandine.lebourgeois@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2024
• First Posted: August 7, 2024
• Study Start: November 8, 2024
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): November 8, 2028
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)