Natural History Study of Clinical and Biological Factors Determining Outcomes in Chronic Graft-Versus-Host Disease

NCT ID: NCT00092235

Last Updated: 2025-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

650 participants

Study Classification

OBSERVATIONAL

Study Start Date

2004-10-26

Brief Summary

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Background:

* Chronic graft-versus-host disease (cGVHD) is a multi-organ alloimmune and autoimmune disorder that occurs following allogeneic hematopoietic stem cell transplantation (alloHSCT). It is characterized by immune dysregulation, immunodeficiency, impaired organ function, and decreased survival.
* Each year about 8000 patients receive allogeneic hematopoietic stem cell transplant (alloHSCT) in North America and about 50% of patients who are transplanted develop cGVHD.
* Chronic GVHD is also a disorder that simultaneously affects many organ systems in highly variable fashion and requires complex and coordinated medical management by multiple medical specialties. There is an urgent need for progress in understanding and effective treatments for cGVHD as it is one of the most serious complications of cancer therapy and hematopoietic stem cell transplantation.

Objectives:

* To establish a multidisciplinary clinic infrastructure for study of the pathogenesis and natural history of cGVHD.
* To prospectively identify clinical and biological prognostic markers in patients with cGVHD
* To develop clinically relevant cGVHD grading scales
* To identify novel biological characteristics of cGVHD and to describe them in the context of clinical history and presentation
* To identify potential clinical and biological markers of cGVHD activity
* To improve understanding of the biology of cGVHD-associated graft-versus-tumor effects
* To identify potential patients for cGVHD treatment protocols at the NCI and NIH

Eligibility:

-Patients age 1 and older referred by the primary transplant physician for the evaluation of chronic graft-versus-host disease independent of underlying diagnosis.

Design:

* Patient undergoes initial clinical and laboratory multispecialty work-up at the NCI cGVHD clinic.
* Minimally invasive biopsies and rarely, deep tissue biopsy may be obtained to confirm the diagnosis and/or rule-out other pathologic process (in adults only).
* Long tem data collection for evaluation of long-term outcomes will be conducted anually as feasible

Detailed Description

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Background:

* Chronic graft-versus-host disease (cGVHD) is a multi-organ alloimmune and autoimmune disorder that occurs following allogeneic hematopoietic stem cell transplantation (alloHSCT). It is characterized by immune dysregulation, immunodeficiency, impaired organ function, and decreased survival.
* Each year about 8000 patients receive allogeneic hematopoietic stem cell transplant (alloHSCT) in North America and about 50% of patients who are transplanted develop cGVHD.
* Chronic GVHD is also a disorder that simultaneously affects many organ systems in highly variable fashion and requires complex and coordinated medical management by multiple medical specialties. There is an urgent need for progress in understanding and effective treatments for cGVHD as it is one of most serious complications of cancer therapy and hematopoietic stem cell transplantation.

Objectives:

* To establish a multidisciplinary clinic infrastructure for study of the pathogenesis and natural history of cGVHD
* To prospectively identify clinical and biological prognostic markers in patients with cGVHD
* To develop clinically relevant cGVHD grading scales
* To identify novel biological characteristics of cGVHD and to describe them in the context of clinical history and presentation
* To identify potential clinical and biological markers of cGVHD activity
* To improve understanding of the biology of cGVHD-associated graft-versus-tumor effects
* To identify potential patients for cGVHD treatment protocols at the NCI and NIH

Eligibility:

-Patients age 1 and older referred by the primary transplant physician for the evaluation of chronic graft-versus-host disease independent of underlying diagnosis.

Design:

* Patient undergoes initial clinical and laboratory multi-specialty work-up at the NCI cGVHD clinic
* Minimally invasive biopsies and rarely, deep tissue biopsy may be obtained to confirm the diagnosis and/or rule-out other pathologic process (in adults only)
* Long term data collection for evaluation of long-term outcomes will be conducted annually as feasible.

Conditions

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Chronic Graft vs. Host Disease

Keywords

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cGVHD-associated graft-versus-tumor effects (GVT) Allo-HSCT controls Leukapheresis Natural History

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort 1

Patients who have undergone an allogeneic stem cell transplant and are diagnosed with cGVHD

No interventions assigned to this group

Cohort 2

Pediatric patients who have undergone an allogeneic stem cell transplant and are diagnosed with cGVHD

No interventions assigned to this group

Cohort 3

Patients who have undergone an allogeneic stem cell transplant and choose to submit biopsy, blood and urine samples only

No interventions assigned to this group

Cohort 4

Patients who have undergone an allogeneic stem cell transplant and are not diagnosed with cGVHD

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Any patient age 1 and older referred by the primary transplant physician for the evaluation of chronic graft-versus-host disease independently of age or underlying diagnosis
2. Patient or the patient's legal representative is able and willing to provide consent.


* Age 1 and older
* Patient has undergone Allo-HSCT
* Patient or the patient's parent/guardian is able and willing to provide consent

Exclusion Criteria

1. Significant medical condition or any other significant circumstance that could in the PIs assessment affect the patient's ability to tolerate, comply, or complete the study
2. Patients who in the PIs assessment have a life expectancy \<3 months.

Note: Because it is not always possible to make a clear clinical distinction between acute and chronic GVHD, patients with acute GVHD are not a-priori excluded until the possibility of chronic GVHD is reliably excluded on the basis of the clinical assessments in the cGVHD clinic.
3. Pregnant women are excluded from this study because multiple tests would need to be excluded for safety of the patient and the fetus.


* Active GVHD
* In the previous three months have received systemic immunosuppressant therapy for the treatment of GVHD
* In the previous three months have received therapy for malignancy
Minimum Eligible Age

1 Year

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Emory University, Department of Pediatrics

UNKNOWN

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Najla El Jurdi, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Najla El Jurdi, M.D.

Role: CONTACT

Phone: (240) 992-4033

Email: [email protected]

References

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Zhao AT, Pirsl F, Steinberg SM, Holtzman NG, Schulz E, Mina A, Mays JW, Cowen EW, Comis LE, Joe GO, Yanovski JA, Pavletic SZ. Metabolic syndrome prevalence and impact on outcomes in patients with chronic graft-versus-host disease. Bone Marrow Transplant. 2023 Dec;58(12):1377-1383. doi: 10.1038/s41409-023-02097-y. Epub 2023 Sep 8.

Reference Type DERIVED
PMID: 37684526 (View on PubMed)

Schulz E, Pirsl F, Holtzman NG, Beshensky D, Cowen EW, Mitchell SA, Steinberg SM, Pavletic SZ. Red cell distribution width as a new prognostic biomarker in refractory chronic graft-versus-host disease. Haematologica. 2024 Jan 1;109(1):298-302. doi: 10.3324/haematol.2023.283646. No abstract available.

Reference Type DERIVED
PMID: 37584292 (View on PubMed)

Beshensky D, Pirsl F, Holtzman NG, Steinberg SM, Mays JW, Cowen EW, Comis LE, Joe GO, Magone MT, Schulz E, Waldman MA, Pavletic SZ. Predictors and significance of kidney dysfunction in patients with chronic graft-versus-host disease. Bone Marrow Transplant. 2023 Oct;58(10):1112-1120. doi: 10.1038/s41409-023-02032-1. Epub 2023 Jul 20.

Reference Type DERIVED
PMID: 37474729 (View on PubMed)

Yang AH, Han MAT, Samala N, Rizvi BS, Marchalik R, Etzion O, Wright EC, Cao L, Hakim FT, Jones E, Kapuria D, Hickstein DD, Fowler D, Kanakry JA, Kanakry CG, Kleiner DE, Koh C, Pavletic SZ, Heller T. Characterization of Hepatic Dysfunction in Subjects Diagnosed With Chronic GVHD by NIH Consensus Criteria. Transplant Cell Ther. 2022 Nov;28(11):747.e1-747.e10. doi: 10.1016/j.jtct.2022.07.017. Epub 2022 Jul 22.

Reference Type DERIVED
PMID: 35878742 (View on PubMed)

Ruben CL, Pirsl F, Steinberg SM, Holtzman NG, Parsons-Wandell L, Baruffaldi J, Curtis LM, Mitchell SA, Kerep AZ, Cowen EW, Berger A, Joe GO, Datiles MB 3rd, Mays JW, Pavletic SZ. Predictors of hematologic malignancy relapse in patients with advanced chronic graft-versus-host disease. Bone Marrow Transplant. 2021 Jul;56(7):1584-1592. doi: 10.1038/s41409-021-01211-2. Epub 2021 Feb 1.

Reference Type DERIVED
PMID: 33526918 (View on PubMed)

Katic M, Pirsl F, Steinberg SM, Dobbin M, Curtis LM, Pulanic D, Desnica L, Titarenko I, Pavletic SZ. Vitamin D levels and their associations with survival and major disease outcomes in a large cohort of patients with chronic graft-vs-host disease. Croat Med J. 2016 Jun 30;57(3):276-86. doi: 10.3325/cmj.2016.57.276.

Reference Type DERIVED
PMID: 27374829 (View on PubMed)

Curtis LM, Datiles MB 3rd, Steinberg SM, Mitchell SA, Bishop RJ, Cowen EW, Mays J, McCarty JM, Kuzmina Z, Pirsl F, Fowler DH, Gress RE, Pavletic SZ. Predictive models for ocular chronic graft-versus-host disease diagnosis and disease activity in transplant clinical practice. Haematologica. 2015 Sep;100(9):1228-36. doi: 10.3324/haematol.2015.124131. Epub 2015 Jun 18.

Reference Type DERIVED
PMID: 26088932 (View on PubMed)

Bassim CW, Fassil H, Dobbin M, Steinberg SM, Baird K, Cole K, Joe G, Comis LE, Mitchell SA, Grkovic L, Edwards D, Mays JW, Cowen EW, Pulanic D, Williams KM, Gress RE, Pavletic SZ. Malnutrition in patients with chronic GVHD. Bone Marrow Transplant. 2014 Oct;49(10):1300-6. doi: 10.1038/bmt.2014.145. Epub 2014 Jul 14.

Reference Type DERIVED
PMID: 25029231 (View on PubMed)

Martires KJ, Baird K, Steinberg SM, Grkovic L, Joe GO, Williams KM, Mitchell SA, Datiles M, Hakim FT, Pavletic SZ, Cowen EW. Sclerotic-type chronic GVHD of the skin: clinical risk factors, laboratory markers, and burden of disease. Blood. 2011 Oct 13;118(15):4250-7. doi: 10.1182/blood-2011-04-350249. Epub 2011 Jul 26.

Reference Type DERIVED
PMID: 21791415 (View on PubMed)

Clark J, Yao L, Pavletic SZ, Krumlauf M, Mitchell S, Turner ML, Cowen EW. Magnetic resonance imaging in sclerotic-type chronic graft-vs-host disease. Arch Dermatol. 2009 Aug;145(8):918-22. doi: 10.1001/archdermatol.2009.78.

Reference Type DERIVED
PMID: 19687424 (View on PubMed)

Imanguli MM, Swaim WD, League SC, Gress RE, Pavletic SZ, Hakim FT. Increased T-bet+ cytotoxic effectors and type I interferon-mediated processes in chronic graft-versus-host disease of the oral mucosa. Blood. 2009 Apr 9;113(15):3620-30. doi: 10.1182/blood-2008-07-168351. Epub 2009 Jan 23.

Reference Type DERIVED
PMID: 19168793 (View on PubMed)

Related Links

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Other Identifiers

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NCT00331968

Identifier Type: -

Identifier Source: nct_alias

04-C-0281

Identifier Type: -

Identifier Source: secondary_id

040281

Identifier Type: -

Identifier Source: org_study_id