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Report for Clinical Trial NCT03828773

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

PTX3 Genetically Stratified Randomized Double-blinded Allocation Event-driven Clinical Trial for Antifungal Prophylaxis in Patients With Acute Myeloid Leukemia

This is a prospective genetically-stratified randomized double-blind event-driven multicentre clinical trial to assess the efficacy of posaconazole-based antifungal prophylaxis allocation strategies for patients with acute myeloid leukemia who receive induction chemotherapy. Allocation strategy based on an invasive mold infection genetic risk will be double-blinded.

NCT03828773 Candidiasis Fungal Infection Acute Myeloid Leukemia Genetic Predisposition Aspergillosis
MeSH:Candidiasis Mycoses Aspergillosis Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Genetic Predisposition to Disease
HPO:Acute megakaryocytic leukemia Acute myeloid leukemia Leukemia Myeloid leukemia

2 Interventions

Name: Posaconazole

Description: Posaconazole is a triazole with broad-spectrum activity, to include Candida species, Aspergillus species, and other fungal pathogens, including the Zygomycetes. Posaconazole is available as slow release tablets (300mg/day) and as intravenous (IV) formulation (300mg/day) and is licensed and approved in Switzerland for the prevention of IFI, including mold and yeast infections, in patients >18 years who are at high risk of developing these types of infection (patients with long-term neutropenia or HCT recipients). Furthermore, international guidelines recommend posaconazole for primary antifungal prophylaxis in high-risk patients, such as AML patients with prolonged neutropenia. Posaconazole is available in Switzerland under the name of Noxafil® in capsules of 100mg, suspension of 40mg/mL and intravenous formulation of 300mg/16.7 mL.
Type: Drug
Group Labels: 2

high-risk PTX3 SNPs low-risk PTX3 SNPs

Name: Fluconazole

Description: Fluconazole is an antifungal with activity against most Candida species. Fluconazole is licensed and approved in Switzerland for prophylaxis of IC in patients with neutropenia induced by chemotherapy or radiotherapy at a daily dose of 200 to 400 mg once daily. Fluconazole (200 mg or 400 mg once daily) is still currently used as primary antifungal prophylaxis (standard of care) in all 7 centers participating in this trial. Fluconazole is available in Switzerland under the name of Diflucan® in capsules of 50 mg, 150 mg and 200 mg and in powder for preparation of suspension (50 mg/5 ml and 200 mg/5 ml (forte)) or perfusion (2 mg/1 ml). Several generics of Diflucan® are authorized in Switzerland. Prescribing Diflucan® or any of its generics will remain at the discretion of and based on the standard operating procedures (SOP) at each institution.
Type: Drug
Group Labels: 2

high-risk PTX3 SNPs low-risk PTX3 SNPs


Primary Outcomes

Description: The cumulative incidence of proven and probable invasive mold infection (IMI) (based on published consensus guidelines by the EORTC/MSG groups and after validation by an independent adjudication committee of infectious disease experts blinded to treatment arms) in the intention-to-treat (ITT) population by day 180.

Measure: Cumulative incidence of proven and probable invasive mold infection (IMI)

Time: Day 180

Secondary Outcomes

Description: The cumulative incidence of possible invasive mold infection (IMI) (based on published consensus guidelines by the EORTC/MSG groups and after validation by an independent adjudication committee of infectious disease experts blinded to treatment arms) by day 180 in the ITT population.

Measure: Cumulative incidence of possible invasive mold infection (IMI)

Time: Day 180

Description: The cumulative incidence of probable and proven Invasive Fungal Infections (IFI) (based on published consensus guidelines by the EORTC/MSG groups and after validation by an independent adjudication committee of infectious disease experts blinded to treatment arms), namely: (a) all IFI, (b) Invasive Aspergillosis (IA) only and (c) Invasive Candidiasis (IC) only in the ITT patient population by day 180.

Measure: Cumulative incidence of probable and proven Invasive Fungal Infections (IFI)

Time: Day 180

Description: The time to probable and proven invasive mold infection (IMI) (based on published consensus guidelines by the EORTC/MSG groups and after validation by an independent adjudication committee of infectious disease experts blinded to treatment arms) during 180 days in the ITT population

Measure: Time to probable and proven invasive mold infection (IMI)

Time: Day 180

Description: The overall survival in the ITT population by day 180.

Measure: Overall survival in the ITT population

Time: Day 180

Description: The time to use of amphotericin B/echinocandin in the ITT population during 180 days.

Measure: Time to use of amphotericin B/echinocandin

Time: Day 180

Description: The number of patient-days of amphotericin B/echinocandin in the ITT population during 180 days.

Measure: Number of patient-days of amphotericin B/echinocandin

Time: Day 180

Description: The frequency/distribution of AE of interest in posaconazole and fluconazole treated participants in the ITT population during 180 days, namely: Hepatotoxicity, defined by elevation of at least one of the following markers above >5x upper limit of normal: transaminases, alkaline phosphatase and/or above >3x upper limit of normal total bilirubin New QTc prolongation, defined as QTc >450 msec for men and >470 msec for women

Measure: Frequency/distribution of adverse events (AE) of interest

Time: Day 180

Description: The cumulative incidence of probable and proven invasive fungal infections (IFI) (based on published consensus guidelines by the EORTC/MSG groups and after validation by an independent adjudication committee of infectious disease experts blinded to treatment arms) , namely: all Invasive Fungal Infections (IFI), all Invasive Mold Infections (IMI), Invasive Aspergillosis (IA) only and Invasive Candidiasis (IC) only in the per protocol (PP) population by day 180.

Measure: Cumulative incidence of probable and proven invasive fungal infections (IFI) in per protocol population

Time: Day 180

Purpose: Prevention

Allocation: Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 rs230561

Methods: Eligible patients will be tested by competitive allele-specific Polymerase Chain Reaction (PCR) from blood-extracted DNA samples for the presence of PTX3 SNPs rs230561 and rs3816527.


2 rs3816527

Methods: Eligible patients will be tested by competitive allele-specific Polymerase Chain Reaction (PCR) from blood-extracted DNA samples for the presence of PTX3 SNPs rs230561 and rs3816527.



HPO Nodes


HPO:
Protein Mutations 0
SNP 0