Clinical trial NCT05866302: Parametric Response Mapping (PRM) for the Detection of Chronic Lung Injury in Hematopoietic Cell Transplant Recipients
Official title: Parametric Response Mapping (PRM) for the Detection of Chronic Lung Injury in Hematopoietic Cell Transplant Recipients. A Multi-center, Observational Trial.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Lung Disease
Hematopoietic Cell Transplantation
Graft Versus Host Disease
Keywords: Parametric response mapping
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-05-19
Enrollment: 375
Sex: ALL
Minimum age (years): 36
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pediatric and adult HCT populations

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.


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.)

Primary outcomes:
measure: 1-year CLD free survival (Cohort 1)
timeFrame: up to 12 months from enrollment
measure: FEV1 decline (Cohort 2)
timeFrame: up to 12 months from enrollment
Secondary outcomes:
measure: PRM profiles in children at the onset of chronic GVHD (Cohort 1)
timeFrame: up to 12 months from enrollment
measure: Correlate PRM profiles at the onset of chronic GVHD with overall survival post-HCT (Cohort 1)
timeFrame: up to 12 months from enrollment
measure: To characterize a PRM profile for CLD in children post-HCT (Cohort 2)
timeFrame: up to 12 months from enrollment
measure: To determine a PRM profile for restrictive lung disease (RLD) in adults with chronic GVHD post-HCT (Cohort 2)
timeFrame: up to 12 months from enrollment
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Hospital
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Boston
country: United States
facility: Dana Farber
state: Massachusetts
city: Ann Arbor
country: United States
facility: The University of Michigan Cancer Center
state: Michigan
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: University of Michigan
name: Gregory Yanik, MD
role: PRINCIPAL_INVESTIGATOR
References: