Non-Invasive Diagnosis of Pediatric Pulmonary Invasive Mold Infections

Study Overview
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Brief Summary
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This study will establish a non-invasive diagnostic approach and evaluate clinical outcomes for children at high-risk for pulmonary invasive fungal infection (PIFI).

Official Title
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Non-Invasive Diagnosis of Pediatric Pulmonary Invasive Mold Infections

Conditions
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Pulmonary Invasive Fungal Infections, Pulmonary Invasive Aspergillosis

Intervention / Treatment
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* Diagnostic Test: Non-Invasive Testing for PIFI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females age > 120 days and < 22 years at any participating site Have at least one of the following conditions associated with a known high incidence of IFI: hematopoietic stem cell transplantation (HSCT), aplastic anemia, or hematologic malignancy New (last 96 hours) radiographic evidence of at least one of the following: at least one nodular lesion greater than or equal to 5 mm in size, a cavitary lesion, a lesion with a halo sign, a lesion with a reverse halo sign, or a lesion with an air crescent sign Prolonged neutropenia (absolute neutrophil count < 500 cells/µl for a period of ≥ 5 consecutive days) in 30 days prior to qualifying chest MRI or CT scan date OR currently receiving systemic therapy for acute or chronic graft-versus-host disease (GVHD) on the date of the qualifying chest MRI or CT scan Subject consent or parental/guardian permission (informed consent) and if appropriate, child assent Exclusion Criteria: Weight <3 kg, so as to not exceed 3 ml/kg in a single blood draw Previous inclusion in this study

Ages Eligible for Study
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Minimum Age: 120 Days
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with possible PIFI<br> | Diagnostic Test: Non-Invasive Testing for PIFI<br>* galactomannan assay, fungal PCRs, cell-free next-generation DNA/RNA sequencing, RNAseq<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Likelihood ratio of the galactomannan assay to return a positive result among subjects determined to have PIFI |  | Baseline | 
| Likelihood ratio of galactomannan assay to return a negative result among subjects determined not to have PIFI |  | Baseline | 
| Likelihood ratio of fungal PCRs (Aspergillus PCR, Mucorales PCR) to return a positive result among subjects determined to have PIFI |  | Baseline | 
| Likelihood ratio of fungal PCRs (Aspergillus PCR, Mucorales PCR) to return a negative result among subjects determined not to have PIFI |  | Baseline | 
| Likelihood ratio of cell-free next generation DNA/RNA sequencing identifying a fungal pathogen to return a positive result among subjects determined to have PIFI |  | Baseline | 
| Likelihood ratio of cell-free next generation DNA/RNA sequencing identifying a fungal pathogen to return a negative result among subjects determined not to have PIFI |  | Baseline | 
| Likelihood ratio of molecular RNAseq platform assessing host immune response to return a positive result among subjects determined to have PIFI |  | Baseline | 
| Likelihood ratio of molecular RNAseq platform assessing host immune response to return a negative result among subjects determined not to have PIFI |  | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome score between patients with possible pulmonary invasive fungal infection managed with empirical antifungal therapy versus an invasive diagnostic procedure | Outcome score inclusive of outcomes and adverse events. Comprehensive clinical outcome score from most to least desirable are score of 1 (survival, improvement in pulmonary nodules, no adverse events related to anti-fungal therapy or invasive diagnostic intervention) to score of 7 (death) | 49 days |