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

NCT05866302 | Recruiting

• 3 other identifiers: UMCC 2022.052HUM00225273R01HL162661
• Study Type: observational
• Target: 375
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Chronic Lung Disease; Hematopoietic Cell Transplantation; Graft Versus Host Disease

Keywords

Parametric response mapping

Outcome Measures

Primary Outcomes (2)

• 1-year CLD free survival (Cohort 1)

  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)

  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 Outcomes (4)

• PRM profiles in children at the onset of chronic GVHD (Cohort 1)

  up to 12 months from enrollment

• Correlate PRM profiles at the onset of chronic GVHD with overall survival post-HCT (Cohort 1)

  up to 12 months from enrollment

• To characterize a PRM profile for CLD in children post-HCT (Cohort 2)

  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)

  up to 12 months from enrollment

Study Arms (2)

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.

Eligibility Criteria

• Age: 36 Months+
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pediatric and adult HCT populations

You may qualify if:

• For both Cohorts 1 and 2:
• Age ≥ 36 months. There is no upper age limit.
• 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.

You may not qualify if:

• 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.)

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (6)

Stanford Hospital

Stanford, California, 94305, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

NOT YET RECRUITING

Dana Farber

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

The University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

MD Anderson

Houston, Texas, 77030, United States

NOT YET RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Samples will be processed and shipped to an outside lab.

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Gregory Yanik, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Answerline

CONTACT

1-800-865-1125; CancerAnswerLine@med.umich.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2023
• First Posted: May 19, 2023
• Study Start: May 30, 2023
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)