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

January 23, 2026 updated by: Nantes University Hospital

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

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Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Posaconazole
Drug: 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Effective residual concentration of posaconazole
Time Frame: On the 8th day of treatment (i.e. after 7 days of treatment)

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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Monitoring of residual plasma concentrations [C]min
Time Frame: From posaconazole baseline up to Day100
Weekly residual plasma concentrations of posaconazole
From posaconazole baseline up to Day100
Description of circumstances leading to posaconazole underdosing
Time Frame: From posaconazole baseline up to Day100
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
Time Frame: From posaconazole baseline up to Day100
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
Time Frame: From posaconazole baseline up to Day100
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)
Time Frame: From posaconazole baseline up to Day100
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
Time Frame: From posaconazole baseline up to Day100
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
Time Frame: From posaconazole baseline up to Day 100
Description of posaconazole-related toxicities according to NCI CTCAE v5 classification
From posaconazole baseline up to Day 100
Description of invasive fungal infections occurring
Time Frame: 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 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
Time Frame: Month 1 post-transplant
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)
Time Frame: 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
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)
Time Frame: 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
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)
Time Frame: 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
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)
Time Frame: 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
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
Time Frame: 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)
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
Time Frame: 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)
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)
Time Frame: 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
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
Time Frame: Up to Day100 and 1 year post-transplant
Post-transplant grade 3 and 4 adverse events (dates of occurrence) (NCI CTCAE version 5 criteria)
Up to Day100 and 1 year post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nantes University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 8, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 15, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 8, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 24, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 7, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 26, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RC23_0186

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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