Study of posaconazole prophylaxis in patients receiving hematopoietic stem cell allograft (allo-HSC) at high risk of invasive fungal infection (IFI): POSALLO study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

8 Nov 2024 → ongoing

Decision date (initial)

2024-07-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ADELMAS 2023

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Efficacy

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 on the 8th day of treatment (i.e. after 7 days of treatment).

Secondary objectives 8

1. Monitoring of residual plasma concentrations [C]min up to Day 100
2. Description of circumstances leading to posaconazole underdosing
3. Description of the reasons for administering posaconazole intravenously (IV)
4. Description of situations leading to initial non-administration or early discontinuation of posaconazole
5. Description of invasive fungal infections occurring
6. Description of patient outcome at Day100 and at 1 year: a) incidence of engraftment, b) overall survival (OS), c) disease-free survival (DFS), d) non-relapse mortality (NRM)
7. Description of patient outcome at Day100 and at 1 year : e)IR : incidence of relapse, f) cumulative incidence of acute GVHD, g) cumulative incidence of chronic GVHD, h) GVHD-free relapse-free survival (GRFS)
8. Grade 3 and 4 post-transplant adverse events

Conditions and MedDRA coding

30 adult patients due to receive an allograft for a myeloid or lymphoid hematological malignancy with an HLA-matched donor from the family or from the international donor file will be included in the hematology departments of the Nantes University Hospital.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patient ≥ 18 years of age. There is no maximum age for inclusion.
2. Allo-HSC transplant for any type of hematological malignancy or benign disease 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
3. Written informed consent prior to protocol initiation
4. ECOG <=2
5. Female of childbearing age with negative pregnancy test and on highly effective contraception during treatment and for 12 months after posaconazole discontinuation
6. Men of childbearing age with highly effective contraception during treatment and for 6 months after stopping posaconazole.
7. Hepatitis B, C and HIV serologies negative
8. Social security affiliation

Exclusion criteria 16

1. Patients with a history of IFI, whether active or resolved at the time of allografting
2. Patient with known intolerance to posaconazole
3. 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
4. patients with congenital or acquired QTc prolongation (QTc >470ms)
5. Cardiac: systolic ejection fraction < 50% by transthoracic ultrasound or isotopic method (isotopic gamma-angiography)
6. Respiratory: DLCOc <40% of theoretical on EFR
7. Renal: creatinine clearance < 50 ml/min (assessed using MDRD method)
8. Hepatic: transaminases greater than 5 times normal or bilirubin greater than 2 times normal
9. Pregnant or breast-feeding women
10. Women or men of childbearing age without effective contraception
11. Serious, uncontrolled concomitant infections
12. Yellow fever vaccination within the last year
13. Patient protected by law (guardianship, curatorship, safeguard of justice)
14. Psychological, family, sociological or geographical conditions that may hinder compliance with the study protocol and follow-up schedule
15. Patient who does not speak or understand French
16. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 8

1. Monitoring of residual plasma concentrations [C]min up to Day 100
2. a)clinical record taken 2/week during hospitalization and then 1/week to describe clinical symptoms leading to malabsorption:nausea,vomiting,diarrhea,mucositis,colitis. Symptom intensity will be assessed (NCI CTCAE v5), b)Adherence to treatment monitored daily during hospitalization (paramedical staff). Once home, adherence assessed 1/week by the doctor in charge of the patient, c)All co-medications recorded throughout course of posaconazole treatment, based on data from patient's medical record
3. The physician in charge of the patient should specify the reason(s) for IV administration of the treatment
4. Description of situations leading to initial non-administration or early discontinuation of posaconazole
5. Description of posaconazole-related toxicities according to NCI CTCAE v5 classification
6. a)Engraftment assessed on hematological reconstitution (number of days of aplasia with PNN <0.5 G/L and platelets < 20, number of platelet and cell transfusions), b) OS : Survival between day 0 of transplantation and date of death or last follow-up, c) DFS : Survival between day 0 of transplant and date of relapse, death or last follow-up, d) NRM : Any death unrelated to relapse or disease progression
7. e) Any documented disease recurrence, f) Acute GVH grade 2-4 according to Mount Sinai criteria, g) Extensive chronic GVH according to NCI criteria, h) GRFS: Median relapse-free survival without grade 3-4 acute GVHD or chronic GVHD requiring systemic treatment
8. Post-transplant grade 3 and 4 adverse events (dates of occurrence) (NCI CTCAE version 5 criteria)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Dr Amandine Le Bourgeois

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Dr Amandine Le Bourgeois

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications