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

Graft Versus Host Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05866302
• Other study ID #: UMCC 2022.052
• Secondary ID: HUM00225273R01HL
• Status: Recruiting
• Start date: May 30, 2023
• Est. completion date: May 2028

Study information

• Verified date: October 2023
• Source: University of Michigan Rogel Cancer Center
• Contact: Cancer Answerline
• Phone: 1-800-865-1125
• Email: CancerAnswerLine[@]med.umich.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 375
• Est. completion date: May 2028
• Est. primary completion date: May 2028
• Gender: All
• Age group: 36 Months and older

Eligibility

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.)

Related Conditions & MeSH terms

• Chronic Lung Disease
• Graft Versus Host Disease
• Graft vs Host Disease
• Hematopoietic Cell Transplantation
• Lung Diseases
• Lung Injury

Locations

Country	Name	City	State
United States	The University of Michigan Cancer Center	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Dana Farber	Boston	Massachusetts
United States	MD Anderson	Houston	Texas
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stanford Hospital	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan Rogel Cancer Center	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	PRM profiles in children at the onset of chronic GVHD (Cohort 1)	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
Secondary	Correlate PRM profiles at the onset of chronic GVHD with overall survival post-HCT (Cohort 1)	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
Secondary	To characterize a PRM profile for CLD in children post-HCT (Cohort 2)	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
Secondary	To determine a PRM profile for restrictive lung disease (RLD) in adults with chronic GVHD post-HCT (Cohort 2)	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