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

NCT ID: NCT05866302

Last Updated: 2025-10-17

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 375 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-05-30
• Study Completion Date: 2028-05-31

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

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.

No interventions assigned to this group

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.)

• Minimum Eligible Age: 36 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gregory Yanik, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

Stanford Hospital

Stanford, California, United States

Site Status: RECRUITING

Emory University

Atlanta, Georgia, United States

Site Status: NOT_YET_RECRUITING

Dana Farber

Boston, Massachusetts, United States

Site Status: NOT_YET_RECRUITING

The University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Site Status: RECRUITING

MD Anderson

Houston, Texas, United States

Site Status: NOT_YET_RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Cancer Answerline

Role: CONTACT

CancerAnswerLine@med.umich.edu

1-800-865-1125

Facility Contacts

Joe Hsu

Role: primary

joehsu@stanford.edu

Kirsten Williams

Role: primary

kirsten.marie.williams@emory.edu

Christine Duncan

Role: primary

chrisin_Duncan@dfci.harvard.edu

Cancer AnswerLine

Role: primary

800-865-1125

Cancer AnswerLine

Role: backup

1-800-865-1125

Ajay Sheshadri

Role: primary

Asheshadri@mdanderson.org

Guan-Shing Cheng

Role: primary

gcheng2@fredhutch.org

Other Identifiers

HUM00225273

Identifier Type: OTHER

Identifier Source: secondary_id

R01HL162661

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UMCC 2022.052

Identifier Type: -

Identifier Source: org_study_id