Chronic Graft vs. Host DiseaseNCT00092235
Natural History Study of Clinical and Biological Factors Determining Outcomes in Chronic Graft-Versus-Host Disease
An observational study of Chronic Graft vs. Host Disease, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 year to 120 years
- Conditions the study is for
- Chronic Graft vs. Host Disease
- How many people
- 650 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Oct 2004to not given
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 120 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients will be selected via referrals or from patients who were on companion clinical protocols at the NIH.
Who may be able to join
- 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
- 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
Who cannot join
- 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
- 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.
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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
Read the detailed description
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
- Chronic Graft vs. Host Disease
- Keywords
- cGVHD-associated graft-versus-tumor effects (GVT), Allo-HSCT controls, Leukapheresis, Natural History
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Patients who have undergone an allogeneic stem cell transplant and are diagnosed with cGVHD | |
| Cohort 2 | Pediatric patients who have undergone an allogeneic stem cell transplant and are diagnosed with cGVHD | |
| Cohort 3 | Patients who have undergone an allogeneic stem cell transplant and choose to submit biopsy, blood and urine samples only | |
| Cohort 4 | Patients who have undergone an allogeneic stem cell transplant and are not diagnosed with cGVHD |
What is being measured
The primary outcome is the main question the study is designed to answer.
To prospectively identify candidate markers for clinical and biological prognostic factors in patients with cGVHD and develop a prognostic model
Patient evaluations resulting in collection of data via several medical specialties; data will be examined individually and against clinical outcomes.
Measured: 2 years + 3 months after protocol entry
To improve our current understanding of the biology of cGVHD-associated graft-versus-tumor effects (GVT).
Studying mechanisms of how cGVHD exerts its anti-cancer effects via laboratory analysis.
Measured: ongoing
To identify potential clinical and biological markers of cGVHD activity
Assessment of risk and outcome as related to molecular markers of pathogenesis and/or stage of disease.
Measured: ongoing
To identify novel biological characteristics of cGVHD and to describe them in the context of clinical history and presentation
Through collection of data via several medical specialties, assess the weight of specific clinical and biological characteristics and disease severity scales for predicting major clinical outcomes.
Measured: ongoing
To establish a multidisciplinary clinic infrastructure for study of pathogenesis and natural history of cGVHD
Assessment of clinical and biological characteristics of cGVHD.
Measured: ongoing
To develop clinically relevant cGVHD grading scales
Develop appropriate staging as a tool for measuring responses or outcomes in clinical studies through prospective collection and analysis of data.
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2004 (estimated)
- Study start26 Oct 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Chronic Graft vs. Host DiseaseStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 650 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Collaborators
- Emory University, Department of Pediatrics
- Responsible party
- Sponsor
- Investigators
- Najla El Jurdi, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00092235
- Sponsor's protocol ID
- 040281
- Other IDs
- 04-C-0281
- Status last verified
- 19 Oct 2026
- First submitted
- 21 Sep 2004
- Last updated
- 21 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Publications
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.
PubMed 37684526Schulz 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.
PubMed 37584292Beshensky 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.
PubMed 37474729Yang 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.
PubMed 35878742Ruben 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.
PubMed 33526918Katic 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.
PubMed 27374829Curtis 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.
PubMed 26088932Bassim 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.
PubMed 25029231Martires 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.
PubMed 21791415Clark 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.
PubMed 19687424Imanguli 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.
PubMed 19168793