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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT00092235

Collaborator

(none)

650

Enrollment

Location

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Graft vs Host Disease

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 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

Study Design

Study Type:

Observational

Anticipated Enrollment :

650 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Oct 26, 2004

Arms and Interventions

Arm	Intervention/Treatment
Cohort 1 Patients who have undergone an allogeneic stem cell transplant and are diagnosed withcGVHD
Cohort 2 Pediatric patients who have undergone an allogeneic stem cell transplant and arediagnosed with cGVHD
Cohort 3 Patients who have undergone an allogeneic stem cell transplant and choose to submitbiopsy, blood and urine samples only
Cohort 4 Patients who have undergone an allogeneic stem cell transplant and are not diagnosed withcGVHD

Outcome Measures

Primary Outcome Measures

To establish a multidisciplinary clinic infrastructure for study of pathogenesis and natural history of cGVHD [Ongoing]
Assessment of clinical and biological characteristics of cGVHD.
To prospectively identify candidate markers for clinical and biological prognostic factors in patients with cGVHD and develop a prognostic model [2 years + 3 months after protocol entry]
Patient evaluations resulting in collection of data via several medical specialties; data will be examined individually and against clinical outcomes
To develop clinically relevant cGVHD grading scales [Ongoing]
Develop appropriate staging as a tool for measuring responses or outcomes in clinical studies through prospective collection andanalysis of data.
To identify novel biological characteristics of cGVHD and to describe them in the context of clinical history and presentation [Ongoing]
Through collection of data via several medical specialties, assess the weight of specific clinical and biological characteristics and diseaseseverity scales for predicting major clinical outcomes.
To identify potential clinical and biological markers of cGVHD activity [Ongoing]
Assessment of risk and outcome as related to molecular markers ofpathogenesis and/or stage of disease.
To improve our current understanding of the biology of cGVHD associated graft-versus-tumor effects (GVT). [Ongoing]
Studying mechanisms of how cGVHD exerts its anti-cancereffects via laboratory analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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 less than 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.