SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03828773

Developed by Shray Alag, 2019.
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: Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Candidiasis Mycoses Aspergillosis Disease Susceptibility 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

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

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:
Acute megakaryocytic leukemia
Genes 1
GATA1
Acute myeloid leukemia
Genes 29
MPL MLF1 NSD1 JAK2 KRAS NPM1 ELANE DKC1 ETV6 TCIRG1 DNAJC21 SRP54 EFL1 FLT3 NUP214 CEBPA THPO MLLT10 RUNX1 PIGA CBFB BRCA2 KIT PICALM SBDS GFI1 SH3GL1 LPP DNMT3A
Leukemia
Genes 125
MPL RNASEH2B KRAS NPM1 TET2 MYD88 TSR2 RPL26 RPL27 TREX1 EFL1 PIGL SCN11A FLT3 PMS2 RPL35A EVC2 ABL1 CEBPA RARA NRAS WAS WIPF1 ATRX SH2B3 PDGFRA RB1 RNASEH2A PDGFRB CALR ARHGAP26 SH3GL1 RPS7 RPS10 NUMA1 GATA1 GATA2 RPS15A APC NSD1 ETV6 TCIRG1 DNAJC21 EVC SRP54 RPS17 NBN RPS19 SAMHD1 MSH2 RPS24 NUP214 RPS26 RPS27 RPS28 RPS29 MLLT10 RUNX1 XRCC4 CBFB CBL BCR ADAR TRIP13 ADA2 NSUN2 CREBBP PICALM GFI1 F13A1 F13B FANCA FANCC BLM FANCD2 FANCE NUTM1 JAK2 IFIH1 TYROBP MSH6 FANCG LIG4 PTPN11 SAMD9L THPO NF1 STS PIGA BRCA2 DYNC2LI1 PIK3CA SBDS GLI1 PIK3R1 BRD4 SETBP1 RNASEH2C LPP BUB1 BUB1B SCN9A SCN10A TREM2 MLF1 MLH1 ELANE DKC1 ATM HAX1 RPL35 GNB1 BUB3 CEP57 TAL1 KIT TAL2 RPL5 EP300 TP53 RPL11 KIF11 RPL15 DNMT3A RPL18
Myeloid leukemia
Genes 12
GATA2 F13A1 CBL ARHGAP26 F13B KRAS PTPN11 SAMD9L KIT SETBP1 NF1 NRAS