Next Generation Pathogen Sequencing for Prediction of Adverse Events

Prediction of Adverse Events in Children and Adolescents With Cancer at High Risk of Infection (PREDSEQ)

The majority of children and adolescents diagnosed with cancer will experience one or more episodes of fever or infection during their course of therapy. The most common microbiologically documented infection is bloodstream infection (BSI), which can be associated with severe sepsis or death. Current methods of diagnosis require a significant load of live bacteria in the blood making early detection difficult. Delayed diagnosis and delayed optimal therapy of BSIs are associated with increased morbidity and mortality.

This study seeks to identify whether next generation sequencing (NGS) of pathogens can identify patients with impending bloodstream infection. This would enable preemptive targeted therapy to replace antibacterial prophylaxis which often leads ot high-density broad-spectrum antibiotic exposure and contributes to subsequent development of antibiotic resistance.

PRIMARY OBJECTIVE:

• To estimate the sensitivity and specificity of next generation pathogen sequencing for prediction of bloodstream infection in children with cancer at high risk of infection.

Study Overview

• Status: Active, not recruiting
• Conditions: Bloodstream Infection

Detailed Description

Plasma samples collected but not required for clinical care (discarded samples) will be collected and stored. Results of NGS will be compared between patients who develop BSI immediately (within 72 hours) after sample collection, those who develop other infectious syndromes, and those who remain well. Clinical data describing baseline information about the patient and malignancy, antibiotic and chemotherapy exposure, microbiology testing, hematology results, and infection-related events will be collected prospectively from the electronic medical record.

An initial exploratory phase will examine approximately 50 participants to determine whether the effectiveness of predicting infections. The study may then enroll up to 200 participants to collection additional data for analysis.

• Study Type: Observational
• Enrollment (Actual): 160

Contacts and Locations

• Study Contact: Name: Joshua Wolf, MBBS, BA; Phone Number: 866-278-5833; Email: referralinfo@stjude.org

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 24 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants who are being treated at St. Jude Children's Research Hospital and who have a high risk of infection.

Description

Inclusion Criteria:

• Under 25 years of age at time of study enrollment
• Undergoing care for cancer at St. Jude
• In a category of patients who are considered by the investigator to be at high risk of infection
• Expected to receive care at St. Jude for at least 7 days

Exclusion Criteria:

• Any condition that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of NGS-positive results	To estimate the sensitivity of next generation pathogen sequencing for prediction of BSI, the proportion of NGS-positive results in all positive BSI cultures will be given.	Once (within 72 hours of enrollment)
Proportion of NGS-negative results	To estimate the specificity of next generation pathogen sequencing for prediction of BSI, the proportion of NGS-negative results in all negative BSI cultures will be given.	Once (within 72 hours of enrollment)

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Collaborators: Karius, Inc.
• Investigators: Principal Investigator: Joshua Wolf, MBBS, BA, St. Jude Children's Research Hospital

Publications and helpful links

General Publications

• Goggin KP, Gonzalez-Pena V, Inaba Y, Allison KJ, Hong DK, Ahmed AA, Hollemon D, Natarajan S, Mahmud O, Kuenzinger W, Youssef S, Brenner A, Maron G, Choi J, Rubnitz JE, Sun Y, Tang L, Wolf J, Gawad C. Evaluation of Plasma Microbial Cell-Free DNA Sequencing to Predict Bloodstream Infection in Pediatric Patients With Relapsed or Refractory Cancer. JAMA Oncol. 2020 Apr 1;6(4):552-556. doi: 10.1001/jamaoncol.2019.4120. Erratum In: JAMA Oncol. 2020 Feb 27;:

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2017
• Primary Completion (Actual): March 1, 2022
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: July 20, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Pediatric; Bloodstream infection (BSI); Next generation pathogen sequencing (NGPS)
• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Infections
• Other Study ID Numbers: PREDSEQ

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No