Posaconazole for Allogeneic hematopoietic stem cell transplantation | Myeloid hematological malignancy | Lymphoid hematological malignancy | High risk of invasive fungal infection

Inclusion criteria

• {"criterion_text":"- Patient ≥ 18 years of age. There is no maximum age for inclusion.\n- 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\n- Written informed consent prior to protocol initiation\n- ECOG <=2\n- Female of childbearing age with negative pregnancy test and on highly effective contraception during treatment and for 12 months after posaconazole discontinuation\n- Men of childbearing age with highly effective contraception during treatment and for 6 months after stopping posaconazole.\n- Hepatitis B, C and HIV serologies negative\n- Social security affiliation"}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measurement of plasma residual posaconazole concentration ([C]min) on Day 8 (after 7 days of treatment). A [C]min > 0.7 mg/L is considered effective."}

Secondary endpoints

• {"endpoint_text":"- Monitoring of residual plasma concentrations [C]min up to Day 100","definition_or_measurement_approach":"Serial measurement of plasma residual posaconazole concentration ([C]min) up to Day 100 (weekly assessments described elsewhere)."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"a) Clinical symptom collection twice weekly during hospitalization then weekly (nausea, vomiting, diarrhea, mucositis, colitis) with intensity graded by NCI CTCAE v5. b) Adherence monitoring daily during hospitalization and weekly after discharge (physician report). c) Recording of all concomitant medications from medical records."}
• {"endpoint_text":"- The physician in charge of the patient should specify the reason(s) for IV administration of the treatment","definition_or_measurement_approach":"Physician documentation of reasons for IV administration (e.g., oral intake difficulties, malabsorption, underdosing)."}
• {"endpoint_text":"- Description of situations leading to initial non-administration or early discontinuation of posaconazole","definition_or_measurement_approach":"Collection and description of circumstances causing initial non-administration or early discontinuation of posaconazole from clinical records."}
• {"endpoint_text":"- Description of posaconazole-related toxicities according to NCI CTCAE v5 classification","definition_or_measurement_approach":"Adverse events graded and described according to NCI CTCAE v5 criteria; attribution to posaconazole recorded."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"a) Engraftment measured by hematologic parameters (days of aplasia with PNN<0.5 G/L and platelets<20 G/L, transfusion counts). b) Overall survival measured from day 0 to death/last follow-up. c) Disease-free survival measured from day 0 to relapse/death/last follow-up. d) Non-relapse mortality: deaths not related to relapse/progression."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Documentation of disease recurrence; acute GVHD graded per Mount Sinai criteria; chronic GVHD per NCI criteria; GRFS defined as relapse-free survival without grade 3-4 acute GVHD or chronic GVHD requiring systemic treatment."}
• {"endpoint_text":"- Post-transplant grade 3 and 4 adverse events (dates of occurrence) (NCI CTCAE version 5 criteria)","definition_or_measurement_approach":"Recording of post-transplant grade 3 and 4 adverse events with dates, classified per NCI CTCAE v5, up to 1 year."}

France

Earliest CTIS Part Ii Submission Date

08-07-2024

Latest Decision Or Authorization Date

23-07-2024

Processing Time Days

15

Number Of Sites

1

Number Of Participants

30

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Nantes

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"ADELMAS 2023","duties_or_roles":"Funding/monetary support","organisation_type":""}