Parametric Response Mapping (PRM) for the Detection of Chronic Lung Injury in Hematopoietic Cell Transplant Recipients

October 16, 2025 updated by: University of Michigan Rogel Cancer Center

Parametric Response Mapping (PRM) for the Detection of Chronic Lung Injury in Hematopoietic Cell Transplant Recipients. A Multi-center, Observational Trial.

The study will have two separate patient cohorts: Cohort 1 will include patients with newly diagnosed chronic graft versus host disease (GVHD), whereas cohort 2 will include patients with newly diagnosed chronic lung disease (CLD). For cohort 1, the primary objective will be to characterize PRM metrics at the onset of chronic GVHD and determine if a PRM signature is present that will predict 1-year CLD free survival. For cohort 2, the primary objective will focus on characterizing PRM at the onset of CLD and determine if PRM can predict the trajectory in lung function decline in affected patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
375

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford Hospital
        • Contact:
        • Principal Investigator:
          • Joe Hsu
    • Georgia
      • Atlanta, Georgia, United States, 30322
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • The University of Michigan Cancer Center
        • Principal Investigator:
          • Gregory A Yanik, MD
        • Contact:
          • Cancer AnswerLine
          • Phone Number: 800-865-1125
        • Contact:
          • Cancer AnswerLine
          • Phone Number: 1-800-865-1125
    • Texas
      • Houston, Texas, United States, 77030
        • Not yet recruiting
        • MD Anderson
        • Contact:
        • Principal Investigator:
          • Ajay Sheshadri
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Research Center
        • Contact:
        • Principal Investigator:
          • Guang-Shing Cheng

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

Pediatric and adult HCT populations

Description

Inclusion Criteria:

  • For both Cohorts 1 and 2:
  • Age ≥ 36 months. There is no upper age limit.
  • Receipt of an allogeneic HCT. There are no exclusions to study entry based upon primary diagnosis, hematopoietic cell source, conditioning regimen, donor type, degree of donor-recipient HLA match, or current organ function.
  • All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
  • Cohort 1 (Chronic Graft Versus Host Disease): Diagnosis of chronic GVHD in at least 1 organ system within the prior 3 months. NIH Consensus Criteria for chronic GVHD are required to establish the diagnosis. (https://pubmed.ncbi.nlm.nih.gov/25529383/)
  • Cohort 2 (Chronic Lung Disease, CLD) Diagnosis of CLD within the prior 100 days, including either Bronchiolitis Obliterans Syndrome (BOS) or Restrictive lung disease (RLD), with each defined as follows: Bronchiolitis Obliterans Syndrome (BOS): (NIH Consensus Criteria)31 a.FEV1 < 75% predicted, with a decline in absolute FEV1 > 10% compared to pretransplant baseline or within the prior 2 years, b.FEV1/VC or FEV1/FVC < 0.7 , c. Absence of an alternative diagnosis, including COPD exacerbation, asthma, and active respiratory tract infection, as determined by appropriate clinical investigations that may include chest imaging, microbiologic cultures, and/or bronchoscopy, d. One of two supportive features of BOS: i. Evidence of air trapping by PFTs: RV>120%, or elevated RV/TLC (>20% of predicted), ii. High resolution chest CT with inspiratory and expiratory cuts that show findings that are consistent with small airways disease including (but not exclusive of) air trapping, bronchial wall thickening, or bronchiectasis. Restrictive Lung Disease (RLD): a. ≥ 20% decline in FEV1 from baseline, coupled with ≥ 10% decline in total lung capacity (TLC) from baseline. If measurements of TLC are not available, then a ≥ 20% decline in FVC from baseline may be substituted for RLD.32, b.Radiographic opacities or infiltrates on chest radiograph or CT. Such changes may include, but are not limited to the presence of ground glass opacities, reticular changes, septal thickening, fibrotic changes or areas of consolidation.
  • Patients unable to perform PFT. For cohort 1, patient's too young (or physically unable) to perform PFT's remain eligible provided they meet all other eligibility criteria. For cohort 2, children too young (or physically unable) to perform PFT's are eligible provided they exhibit both clinical and radiographic features (on CT) consistent with CLD. Clinical features would include dyspnea, cough, and/or SpO2 < 93% on room air. Radiographic features may include, but are not limited to the presence of air trapping, bronchial wall thickening, or bronchiectasis.

Exclusion Criteria:

  • Relapse of a patient's primary malignancy post-HCT, or the development of any secondary "hematologic" malignancy post-HCT.
  • The presence of an active, uncontrolled infection.
  • Patients who would require intubation solely for the purposes of obtaining a CT scan for PRM imaging. (In contrast, if a clinical CT is being performed as routine medical care to evaluate a patient's lung function, the patient is eligible and PRM imaging may be performed from that CT.)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Cohort 1: Newly diagnosed chronic GVHD
All subjects will undergo a non-contrast, high resolution CT scan with inspiratory and expiratory imaging, pulmonary function testing (PFT) and serologic biomarker studies upon entry. A total of 300 subjects (200 adults, 100 pediatric) will be enrolled. Patients in cohort 1 who develop CLD prior to the 12-month period will transition to cohort 2 at that time. PFT is recommended every 3 months over a 12 month period. Plasma samples will be collected at entry and at 12 months.
Cohort 2: Newly diagnosed chronic lung disease (CLD)
All subjects will undergo a non-contrast, high resolution CT scan with inspiratory and expiratory imaging, pulmonary function testing (PFT) and serologic biomarker studies upon entry. A total of 75 subjects (50 adults, 25 pediatric) will be enrolled. PFT is recommended every 3 months over a 12 month period. Plasma samples will be collected at entry and at 12 months.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
1-year CLD free survival (Cohort 1)
Time Frame: up to 12 months from enrollment
The time to develop CLD or death over 12 months of follow-up in both pediatric and adult subjects will be determined. we will classify subjects into comparison groups of (1) high PRMfSAD (>30%), (2) high PRMPD (>40%) or (3) neither high PRMfSAD nor high PRMPD (PRMNorm group). The two primary analyses are to compare 1-year CLD-free survival between the high PRMfSAD and PRMNorm groups and separately between the high PRMPD and PRMNorm groups, using two-sided, two-sample logrank tests with an overall 5% type I error, adjusted for 2 comparisons using the Bonferroni method
up to 12 months from enrollment
FEV1 decline (Cohort 2)
Time Frame: up to 12 months from enrollment
Trajectory of FEV1 decline over a 12-month period in patients with newly diagnosed CLD. To evaluate PRM as a predictor of "lung function decline" in patients with an established diagnosis of CLD.
up to 12 months from enrollment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
PRM profiles in children at the onset of chronic GVHD (Cohort 1)
Time Frame: up to 12 months from enrollment
Pediatric subjects will be enrolled into one of 2 strata (PFT+ vs PFTnull), PRM imaging with whole lung volumetric CT scans will be performed at baseline, using low dose CT techniques in children. Strata 1 (PFT+), the occurrence of CLD will be defined using NIH Consensus Criteria for BOS, or ISHLT criteria for RLD. Stratum 2 (PFTnull), radiographic findings of obstructive or restrictive lung disease on CT, plus clinical symptoms (dyspnea, or hypoxia) will be required to establish a diagnosis of CLD, in lieu of PFTs. PRM profile will be reported as percent functional small airway disease (PRMfSAD), emphysema (PRMEmph), parenchymal lung disease (PRMPD), and normal lung parenchyma (PRMNorm), in relation to the total lung volume.
up to 12 months from enrollment
Correlate PRM profiles at the onset of chronic GVHD with overall survival post-HCT (Cohort 1)
Time Frame: up to 12 months from enrollment
Subjects will be enrolled into one of 2 strata (PFT+ vs PFTnull), PRM imaging with whole lung volumetric CT scans will be performed at baseline.. For patients in strata 1 (PFT+), the occurrence of CLD will be defined using NIH Consensus Criteria for BOS, or ISHLT criteria for RLD. For patients in stratum 2 (PFTnull), radiographic findings of obstructive or restrictive lung disease (i.e. air trapping, bronchiectactic changes, interstitial fibrosis) on CT, plus clinical symptoms (dyspnea, or hypoxia) will be required to establish a diagnosis of CLD, in lieu of PFTs. Histograms of PRMfSAD, PRMPD, PRMEmph, and PRMNorm values will be displayed by pediatric stratum and overall, with means ± standard errors superimposed on the plots. PRM profile will be reported as percent functional small airway disease (PRMfSAD), emphysema (PRMEmph), parenchymal lung disease (PRMPD), and normal lung parenchyma (PRMNorm), in relation to the total lung volume.
up to 12 months from enrollment
To characterize a PRM profile for CLD in children post-HCT (Cohort 2)
Time Frame: up to 12 months from enrollment
We will have approximately 90% power to detect correlations > 0.47 using 2-sided 1-sample correlation tests. This is a conservative estimate involving only the adult participants, with power increasing once pediatric participants are included in the analysis. In a secondary analysis we will use linear mixed effects models to study FEV1 predicted trajectories after CLD onset, as a function of PRM values. We will explore interactions between PRM values and time post-CLD when modeling FEV1 predicted values over time. PRM profile will be reported as percent functional small airway disease (PRMfSAD), emphysema (PRMEmph), parenchymal lung disease (PRMPD), and normal lung parenchyma (PRMNorm), in relation to the total lung volume.
up to 12 months from enrollment
To determine a PRM profile for restrictive lung disease (RLD) in adults with chronic GVHD post-HCT (Cohort 2)
Time Frame: up to 12 months from enrollment
We will have approximately 90% power to detect correlations > 0.47 using 2-sided 1-sample correlation tests. This is a conservative estimate involving only the adult participants, with power increasing once pediatric participants are included in the analysis. In a secondary analysis we will use linear mixed effects models to study FEV1 predicted trajectories after CLD onset, as a function of PRM values. We will explore interactions between PRM values and time post-CLD when modeling FEV1 predicted values over time. PRM profile will be reported as percent functional small airway disease (PRMfSAD), emphysema (PRMEmph), parenchymal lung disease (PRMPD), and normal lung parenchyma (PRMNorm), in relation to the total lung volume.
up to 12 months from enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Michigan Rogel Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gregory Yanik, MD, University of Michigan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 30, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 13, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 9, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 19, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 20, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 16, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UMCC 2022.052
  • HUM00225273 (Other Identifier: University of Michigan)
  • R01HL162661 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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