Clinical trial NCT00092235: Natural History Study of Clinical and Biological Factors Determining Outcomes in Chronic Graft-Versus-Host Disease
Official title: Natural History Study of Clinical and Biological Factors Determining Outcomes in Chronic Graft-Versus-Host Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Graft vs. Host Disease
Keywords: cGVHD-associated graft-versus-tumor effects (GVT)
Allo-HSCT controls
Leukapheresis
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: Emory University, Department of Pediatrics
First posted: 2004-09-22
Enrollment: 650
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be selected via referrals or from patients who were on companion clinical protocols at the NIH.

Brief 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.
* 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: 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.

Eligibility criteria: * 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.

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.

Inclusion Criteria for control subjects without cGVHD:

* 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 for control subjects without cGVHD:

* 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

Primary outcomes:
measure: To prospectively identify candidate markers for clinical and biological prognostic factors in patients with cGVHD and develop a prognostic model
timeFrame: 2 years + 3 months after protocol entry
measure: To improve our current understanding of the biology of cGVHD-associated graft-versus-tumor effects (GVT).
timeFrame: ongoing
measure: To identify potential clinical and biological markers of cGVHD activity
timeFrame: ongoing
measure: To identify novel biological characteristics of cGVHD and to describe them in the context of clinical history and presentation
timeFrame: ongoing
measure: To establish a multidisciplinary clinic infrastructure for study of pathogenesis and natural history of cGVHD
timeFrame: ongoing
measure: To develop clinically relevant cGVHD grading scales
timeFrame: ongoing
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Najla El Jurdi, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.