Next Generation Pathogen Sequencing for Prediction of Adverse Events

• ClinicalTrials.gov Identifier: NCT03226158
• Recruitment Status: Active, not recruiting
• First Posted: July 21, 2017
• Last Update Posted: May 6, 2024
• Sponsor: St. Jude Children's Research Hospital
• Collaborator: Karius, Inc.
• Information provided by (Responsible Party): St. Jude Children's Research Hospital

Tracking Information

• First Submitted Date: July 20, 2017
• First Posted Date: July 21, 2017
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: August 9, 2017
• Actual Primary Completion Date: March 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 20, 2017)

• Proportion of NGS-positive results [ Time Frame: Once (within 72 hours of enrollment) ]
  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.
• Proportion of NGS-negative results [ Time Frame: Once (within 72 hours of enrollment) ]
  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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Next Generation Pathogen Sequencing for Prediction of Adverse Events
• Official Title: Prediction of Adverse Events in Children and Adolescents With Cancer at High Risk of Infection (PREDSEQ)

Brief Summary

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.

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
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Plasma samples collected but not required for clinical care will undergo next generation pathogen sequencing.

• 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.
• Condition: Bloodstream Infection
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• 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;:

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 29, 2023): 160
• Original Estimated Enrollment (submitted: July 20, 2017): 200
• Estimated Study Completion Date: May 1, 2025
• Actual Primary Completion Date: March 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 24 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03226158
• Other Study ID Numbers: PREDSEQ
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: St. Jude Children's Research Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: St. Jude Children's Research Hospital
• Original Study Sponsor: Same as current
• Collaborators: Karius, Inc.

Investigators

• Principal Investigator: Joshua Wolf, MBBS, BA; St. Jude Children's Research Hospital

• PRS Account: St. Jude Children's Research Hospital
• Verification Date: May 2024