Immunologic Features of Respiratory Failure in Pediatric Hematopoietic Cell Transplantation (HCT) Recipients and Pediatric Oncology Patients

This study is being done because researchers want to learn more about genes that control the immune response in the participant's lungs and blood when the participant have lung disease leading to respiratory failure.

Primary Objective

To evaluate the feasibility of performing single cell gene expression analyses on tracheal aspirates from immunocompromised pediatric patients with immune compromising conditions, including HCT recipients.

Secondary Objectives

• To assess whether cell composition and activation states in longitudinally obtained tracheal aspirate and blood samples are able to distinguish unique immunopathology for each of the early post-HCT lung diseases.
• To assess whether cell composition and activation states in longitudinally obtained tracheal aspirate and blood samples are different between two immunodeficient patient populations (alloHCT vs non alloHCT) with lung disease and respiratory failure.
• To test the hypothesis that allogeneic T cell responses are implicated in the pathogenesis of early post-HCT lung diseases.

Exploratory Objectives

To correlate immune cell signaling in the lower respiratory tract and blood of patients with early post-HCT lung diseases with the presence or absence of pathogenic microbes at each site.

To explore HLA testing in Tracheal Aspirates in samples where enough cells are present.

Study Overview

• Status: Completed
• Conditions: Respiratory Failure; Respiratory Disease

Detailed Description

This study involves a Tracheal aspirate, Bronchoalveolar lavage (BAL), and blood samples. The tracheal aspirates and blood samples will be obtained within 24 hours of intubation, then twice more every 3 -4 days, and then once a week until the patient is extubated. If the primary treatment team performs bronchoscopy with BAL, then an aliquot of residual BAL fluid will be obtained.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

• Study Contact: Name: Tim Flerlage, MD; 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 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All participants who meet eligibility criteria and consent to enrollment on the study.

Description

Inclusion Criteria:

• Participant is age 0 to 21 years old
• Participant has acute respiratory failure due to primary pulmonary disease and is expected to receive invasive mechanical ventilation for more than 48 hours

Exclusion Criteria:

• The primary etiology of respiratory failure is not related to primary pulmonary disease
• Aspiration is present
• The participant has a tracheostomy
• If the patient has undergone HCT, they are more than 100 days removed from HCT
• Has a diagnosis of severe combined immunodeficiency syndrome (SCIDS)
• The primary on-service team feels obtaining a study sample would be unsafe for any reason.
• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Subgroup 1; Composed of HCT patients with respiratory failure requiring intubation and mechanical ventilation.
Subgroup 2; Composed of oncology patients (solid tumor or leukemia patients) who have not undergone HCT and who have respiratory failure requiring intubation and mechanical ventilation.
Subgroup 3; Composed of chimeric antigen T-cell receptor infusion recipients who have respiratory failure requiring intubation and mechanical ventilation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of performing single cell gene expression analyses on tracheal aspirates	Feasibility is a qualitative binary outcome (Yes and No), based on the success of recovery of more than 100,000 live cells from a tracheal aspirate and blood sample from five of the first ten allo HCT patients enrolled on the study protocol.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success of distinguishing unique immunopathology for each of the early post-HCT lung diseases	This is a qualitative binary outcome (Yes/No) by applying single cell gene expression analyses to cells from tracheal aspirates and blood of patients with post-HCT lung diseases. With visualization techniques, a call of success (Yes/No) will be made.	4 years
: Difference of cell composition and activation states between two immunodeficient patient populations (alloHCT vs non alloHCT) with lung disease and respiratory failure.	This is a qualitative binary outcome (different vs not different) obtained from visualization.	4 years
Whether allogeneic T cell responses are implicated in the pathogenesis of early post-HCT lung diseases.	This is a qualitative binary endpoint assessed by visualization.	4 years

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Tim Flerlage, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2021
• Primary Completion (Actual): August 30, 2023
• Study Completion (Actual): August 30, 2023

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: April 17, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Insufficiency; Respiration Disorders; Respiratory Tract Diseases
• Other Study ID Numbers: HCTALI

Drug and device information, study documents

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