Immune Mediated Disorders After Allogeneic Hematopoietic Cell Transplantation

Longitudinal Study of Immune Mediated Disorders After Allogeneic Hematopoietic Cell Transplantation (HCT)

The purpose of this research study is to better understand the onset and course of graft versus host disease (GVHD)and other immune-mediated disorders after stem cell transplant.

Study Overview

• Status: Completed
• Conditions: Bronchiolitis Obliterans; Graft vs Host Disease; Cutaneous Sclerosis

Detailed Description

Allogeneic hematopoietic cell transplantation (HCT) is the only known curative option for many hematologic disorders. After transplantation, many patients develop immune mediated disorders that may be life-threatening such as graft versus host disease (GVHD). The morbidity and mortality associated with HCT-associated immune mediated disorders are major barriers to successful use of transplantation to cure rare hematologic malignancies such as leukemia, lymphoma, multiple myeloma, myelodysplastic/myeloproliferative syndromes amongst other diseases.

With this study, the investigators will investigate the biologic basis for immune mediated disorders after allogeneic HCT, focusing on those developing cutaneous sclerosis, bronchiolitis obliterans syndrome, late acute GVHD and chronic GVHD. The study will enroll 1118 (1018 adults and 100 children) allogeneic HCT patients over a three year period. Subjects will be followed for two years and monitored closely for development of immune mediated disorders. This study will have 5 study visits at day 1, 100, 180, 365, and 730. During these visits, a physical assessment, medication review, blood and urine collection will occur.

If a subject develops an immune mediated disordered, they will be monitored at 3 months, 6 months, 1 year and then annually from the date of diagnosis. During these study visits, a physical assessment, IMD status, and medication review as well as blood and urine collection will occur.

• Study Type: Observational
• Enrollment (Actual): 911

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University St. Louis
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients who are preparing for or have recently received an allogeneic hematopoietic cell transplant

Description

Inclusion Criteria:

• Planned or completed first allogeneic stem cell transplant (any conditioning regimen, graft source, donor type and GVHD prophylaxis regimen)
• Signed, informed consent and, if applicable, child assent

Exclusion Criteria:

• Inability to comply with study procedures
• Anticipated survival less than 6 months due to co-morbid disease
• Autoimmune disorder or inherited immunodeficiency before HCT
• Diagnosis of late acute or chronic GVHD prior to study enrollment
• Hematologic relapse or chemotherapy refractory disease at restaging within 1 month of HCT or at the time of enrollment (e.g., > 5% blasts for leukemia; poorly responsive lymphoma)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Controls; Never develop an immune mediated disorder
Immune Mediated Disorder; Develop an immune mediated disorder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The prevalence of immune mediated disorders	The prevalence of: Persistent, recurrent or late onset acute GVHD; Cutaneous Sclerosis; Bronchiolitis Obliterans Syndrome; Chronic GVHD	Diagnosis of IMD and at 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Banked blood and urine samples	Summarized as the percentage of compliance for each center and for the study as a whole	At 2 years

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stephanie Lee, MD, MPH, Fred Hutchinson Cancer Center

Publications and helpful links

General Publications

• Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: September 20, 2010
• First Submitted That Met QC Criteria: September 20, 2010
• First Posted (Estimate): September 21, 2010

Study Record Updates

• Last Update Posted (Estimate): October 7, 2016
• Last Update Submitted That Met QC Criteria: October 6, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Bone Marrow Transplantation; Allogeneic Hematopoietic Cell Transplantation; Graft vs Host Disease; Peripheral Blood Stem Cell Transplantation; Umbilical Cord Blood Stem Cell Transplantation
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis; Bronchiolitis Obliterans; Graft vs Host Disease
• Other Study ID Numbers: RDCRN 6501; U54CA163438 (U.S. NIH Grant/Contract); RDCRN-6501 (Other Identifier: DMCC); 2342.00 (Other Identifier: FHCRC)