Using parametric response mapping to detect lung injury in transplant patients

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

This study is testing if a new imaging method can help predict lung problems in transplant patients who have chronic graft versus host disease or chronic lung disease.

Quick facts

• Study type: Observational
• Enrollment: 375 (estimated)
• Ages: 36 Months and up
• Sex: All
• Sponsor: University of Michigan Rogel Cancer Center (Academic / other)
• Locations: 6 sites (Stanford, California and 5 other locations)
• Trial ID: NCT05866302 on ClinicalTrials.gov

What this trial studies

This observational study involves two patient cohorts: one with newly diagnosed chronic graft versus host disease (GVHD) and another with newly diagnosed chronic lung disease (CLD). The first cohort aims to characterize parametric response mapping (PRM) metrics at the onset of chronic GVHD to predict one-year CLD-free survival. The second cohort focuses on characterizing PRM at the onset of CLD to determine its ability to predict lung function decline. The study will include patients aged 36 months and older who have received an allogeneic hematopoietic cell transplant.

Who should consider this trial

Good fit: Ideal candidates include patients aged 36 months and older who have recently been diagnosed with chronic GVHD or chronic lung disease following an allogeneic hematopoietic cell transplant.

Not a fit: Patients who do not have chronic GVHD or chronic lung disease, or those who have not undergone an allogeneic hematopoietic cell transplant, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved early detection and management of chronic lung injuries in hematopoietic cell transplant recipients.

How similar studies have performed: Other studies utilizing parametric response mapping have shown promise in similar contexts, suggesting potential for success in this approach.

Eligibility criteria

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.)

Where this trial is running

Stanford, California and 5 other locations

• Stanford Hospital — Stanford, California, United States (Recruiting)
• Emory University — Atlanta, Georgia, United States (Not_yet_recruiting)
• Dana Farber — Boston, Massachusetts, United States (Not_yet_recruiting)
• The University of Michigan Cancer Center — Ann Arbor, Michigan, United States (Recruiting)
• MD Anderson — Houston, Texas, United States (Not_yet_recruiting)
• Fred Hutchinson Cancer Research Center — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Gregory Yanik, MD — University of Michigan
• Study coordinator: Cancer Answerline

Conditions Chronic Lung Disease; Hematopoietic Cell Transplantation; Graft Versus Host Disease; Parametric response mapping