Patients Treated for Chronic Granulomatous Disease (CGD) Since 1995

NCT02082353 | Unknown

• 2 other identifiers: DAIT RDCRN PIDTC-6903U54AI082973
• Study Type: observational
• Target: 1,480
• Locations: 2 countries
• Sites: 44

Brief Summary

Chronic granulomatous disease (CGD) is an inherited immune system abnormality in which bone marrow transplantation (BMT) has been shown to be curative. However the risks of transplantation are high and not all patients with CGD may need to undergo this high risk procedure. This study will determine the long term medical condition and daily functioning of participants with CGD after a transplant and if possible, compare these results to participants who do not undergo a transplant.

Conditions

Granulomatous Disease, Chronic

Keywords

Granulomatous Disease, Chronic; Hematopoietic Stem Cell Transplantation (HSCT); bone marrow transplant (BMT); non-transplant; factors associated with best outcomes of transplant in CGD

Outcome Measures

Primary Outcomes (1)

• Death

  The event analyzed is death from any cause. The time from HCT to death or last follow up will be analyzed. Cause of death will also be collected. Surviving patients will be censored at the time of last observation.

  HCT to date of death, up to an expected average of 3 years

Secondary Outcomes (4)

• Engraftment

  an expected average of 3 years

• Quality of Life Measures

  an expected average of 3 years

• Infections

  an expected average of 3 years

• Autoimmune or inflammatory complications

  an expected average of 3 years

Study Arms (4)

Retrospective CGD Cohort

Longitudinal analysis

Prospective CGD Cohort

Longitudinal analysis

HCT CGD Cohort

Cross-sectional analysis

Conventional Non-Transplant CGD Cohort

Longitudinal analysis

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Institutions participating in Rare Diseases Clinical Research Network (RDCRN)

You may qualify if:

• CGD Patients Undergoing Transplant 1995 to Present with Birth Year In or After 1988
• CGD Patients will be Defined by both Defective Neutrophil NADPH Oxidase Function and by Clinical History Consistent with CGD
• Patients must have both of:
• A functional assay demonstrating abnormal NADPH oxidase function (see A below); AND Clinical history consistent with CGD (see B below).
• \*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*
• Patients must have both "A" and "B":
• A. Function: Assays of NADPH Oxidase Function
• I. Dihydrorhodamine (DHR) Assay:
• Blood sample was obtained at a time when patient was clinically stable and not critically ill, with control samples performed simultaneously indicating a qualified assay; and
• Assay unequivocally demonstrates CGD with an stimulation index (SI) SI \< 35 or equivalent. Assay report, including mean fluorescence intensity (MFI) from unstimulated and stimulated samples and gating strategy, must be de-identified and provided. OR
• II. Nitroblue Tetrazolium Oxidation Test (NBT):
• o Diagnostic of CGD (reported as reduced granulocyte oxidative response). Report must be de-identified and provided. AND
• B. Clinical History: One or More of the Following:
• Severe and/or recurrent infection (liver, perirectal or lung abscess; pneumonia; adenitis; or osteomyelitis) due to, for example, Staphylococcus aureus, Burkholderia sp, Serratia marcescens, non-albicans Candida sp, Aspergillus sp or other mold; or Nocardia sp or other deep tissue infection characteristic of CGD
• Sterile granulomatous disease in respiratory, gastrointestinal or urogenital tracts; or Crohn's disease-like colitis

You may not qualify if:

• Presence of other primary immunodeficiency syndromes that do not meet the clinical and laboratory criteria for CGD.
• Rac2 Deficiency
• Myeloperoxidase Deficiency (MPO Deficiency)
• Glutathione deficiency
• Leukocyte adhesion deficiency syndrome
• Non-transplant subjects:
• In addition, non-transplant subjects will be excluded if the only assessment of oxidase function available is the nitroblue tetrazolium (NBT) test (a non-quantitative test).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Rare Diseases Clinical Research Network: collaborator
• Primary Immune Deficiency Treatment Consortium (PIDTC): collaborator

Study Sites (44)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

UCLA

Los Angeles, California, 90095-1752, United States

Location

Lucile Salter Packard Children's Hospital at Stanford

Palo Alto, California, 94304, United States

Location

University of California (UCSF) Benioff Children's Hospital

San Francisco, California, 94143-1278, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Alfred I. duPont Hospital for Children/Nemours

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center, Washington DC

Washington D.C., District of Columbia, 20010-2970, United States

Location

Johns Hopkins All Children's Hospital - St. Petersburg, FL

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta, Emory University

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Children's Hospital of New Orleans at LSUHSC

New Orleans, Louisiana, 70118, United States

Location

NIH Clinical Center Genetic Immunotherapy Section

Bethesda, Maryland, 20892, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Hospital

Rochester, Minnesota, 55902, United States

Location

Cardinal Glennon Children's Hospital/ St. Louis University

St Louis, Missouri, 63104, United States

Location

Washington University/ St.Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan-kettering Cancer Center

New York, New York, 10065, United States

Location

University of Rochester Medical Center/ Golisano Children's Hospital

Rochester, New York, 14642, United States

Location

New York Medical College, Maria Fareri Children's Hospital

Valhalla, New York, 10595, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies/ University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

Texas Children's Hospital, Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Methodist Children's Hospital of South Texas/Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Primary Children's Medical Center/ University of Utah

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Research Institute

Seattle, Washington, 98101, United States

Location

University of Wisconsin/ American Family Children's Hospital

Madison, Wisconsin, 53705-2275, United States

Location

Children's Hospital of Wisconsin-Milwaukee

Milwaukee, Wisconsin, 53226, United States

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Cancer Care Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1XB, Canada

Location

CHU St. Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (11)

• Griffith LM, Cowan MJ, Kohn DB, Notarangelo LD, Puck JM, Schultz KR, Buckley RH, Eapen M, Kamani NR, O'Reilly RJ, Parkman R, Roifman CM, Sullivan KE, Filipovich AH, Fleisher TA, Shearer WT. Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: current status and critical needs. J Allergy Clin Immunol. 2008 Dec;122(6):1087-96. doi: 10.1016/j.jaci.2008.09.045. Epub 2008 Nov 6.

  PMID: 18992926 BACKGROUND

• Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Pai SY, Ballard B, Bauer SC, Bleesing JJ, Boyle M, Brower A, Buckley RH, van der Burg M, Burroughs LM, Candotti F, Cant AJ, Chatila T, Cunningham-Rundles C, Dinauer MC, Dvorak CC, Filipovich AH, Fleisher TA, Bobby Gaspar H, Gungor T, Haddad E, Hovermale E, Huang F, Hurley A, Hurley M, Iyengar S, Kang EM, Logan BR, Long-Boyle JR, Malech HL, McGhee SA, Modell F, Modell V, Ochs HD, O'Reilly RJ, Parkman R, Rawlings DJ, Routes JM, Shearer WT, Small TN, Smith H, Sullivan KE, Szabolcs P, Thrasher A, Torgerson TR, Veys P, Weinberg K, Zuniga-Pflucker JC; workshop participants. Primary Immune Deficiency Treatment Consortium (PIDTC) report. J Allergy Clin Immunol. 2014 Feb;133(2):335-47. doi: 10.1016/j.jaci.2013.07.052. Epub 2013 Oct 15.

  PMID: 24139498 RESULT

• Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Shearer WT, Burroughs LM, Torgerson TR, Decaluwe H, Haddad E; workshop participants. Primary Immune Deficiency Treatment Consortium (PIDTC) update. J Allergy Clin Immunol. 2016 Aug;138(2):375-85. doi: 10.1016/j.jaci.2016.01.051. Epub 2016 Apr 22.

  PMID: 27262745 RESULT

• Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, Kapoor N, Hanson IC, Filipovich AH, Jyonouchi S, Sullivan KE, Small TN, Burroughs L, Skoda-Smith S, Haight AE, Grizzle A, Pulsipher MA, Chan KW, Fuleihan RL, Haddad E, Loechelt B, Aquino VM, Gillio A, Davis J, Knutsen A, Smith AR, Moore TB, Schroeder ML, Goldman FD, Connelly JA, Porteus MH, Xiang Q, Shearer WT, Fleisher TA, Kohn DB, Puck JM, Notarangelo LD, Cowan MJ, O'Reilly RJ. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014 Jul 31;371(5):434-46. doi: 10.1056/NEJMoa1401177.

  PMID: 25075835 RESULT

• Haddad E, Allakhverdi Z, Griffith LM, Cowan MJ, Notarangelo LD. Survey on retransplantation criteria for patients with severe combined immunodeficiency. J Allergy Clin Immunol. 2014 Feb;133(2):597-9. doi: 10.1016/j.jaci.2013.10.022. Epub 2013 Dec 10. No abstract available.

  PMID: 24331379 RESULT

• Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. J Allergy Clin Immunol. 2014 Apr;133(4):1092-8. doi: 10.1016/j.jaci.2013.09.044. Epub 2013 Nov 28.

  PMID: 24290292 RESULT

• Dvorak CC, Cowan MJ, Logan BR, Notarangelo LD, Griffith LM, Puck JM, Kohn DB, Shearer WT, O'Reilly RJ, Fleisher TA, Pai SY, Hanson IC, Pulsipher MA, Fuleihan R, Filipovich A, Goldman F, Kapoor N, Small T, Smith A, Chan KW, Cuvelier G, Heimall J, Knutsen A, Loechelt B, Moore T, Buckley RH. The natural history of children with severe combined immunodeficiency: baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901. J Clin Immunol. 2013 Oct;33(7):1156-64. doi: 10.1007/s10875-013-9917-y. Epub 2013 Jul 2.

  PMID: 23818196 RESULT

• Griffith LM, Cowan MJ, Notarangelo LD, Puck JM, Buckley RH, Candotti F, Conley ME, Fleisher TA, Gaspar HB, Kohn DB, Ochs HD, O'Reilly RJ, Rizzo JD, Roifman CM, Small TN, Shearer WT; Workshop Participants. Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management. J Allergy Clin Immunol. 2009 Dec;124(6):1152-60.e12. doi: 10.1016/j.jaci.2009.10.022.

  PMID: 20004776 RESULT

• Marsh RA, Leiding JW, Logan BR, Griffith LM, Arnold DE, Haddad E, Falcone EL, Yin Z, Patel K, Arbuckle E, Bleesing JJ, Sullivan KE, Heimall J, Burroughs LM, Skoda-Smith S, Chandrakasan S, Yu LC, Oshrine BR, Cuvelier GDE, Thakar MS, Chen K, Teira P, Shenoy S, Phelan R, Forbes LR, Chellapandian D, Davila Saldana BJ, Shah AJ, Weinacht KG, Joshi A, Boulad F, Quigg TC, Dvorak CC, Grossman D, Torgerson T, Graham P, Prasad V, Knutsen A, Chong H, Miller H, de la Morena MT, DeSantes K, Cowan MJ, Notarangelo LD, Kohn DB, Stenger E, Pai SY, Routes JM, Puck JM, Kapoor N, Pulsipher MA, Malech HL, Parikh S, Kang EM; submitted on behalf of the Primary Immune Deficiency Treatment Consortium. Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT. J Clin Immunol. 2019 Oct;39(7):653-667. doi: 10.1007/s10875-019-00659-8. Epub 2019 Aug 2.

  PMID: 31376032 RESULT

• Chandrasekaran P, Han Y, Zerbe CS, Heller T, DeRavin SS, Kreuzberg SA, Marciano BE, Siu Y, Jones DR, Abraham RS, Stephens MC, Tsou AM, Snapper S, Conlan S, Subramanian P, Quinones M, Grou C, Calderon V, Deming C, Leiding JW, Arnold DE, Logan BR, Griffith LM, Petrovic A, Mousallem TI, Kapoor N, Heimall JR, Barnum JL, Kapadia M, Wright N, Rayes A, Chandra S, Broglie LA, Chellapandian D, Deal CL, Grunebaum E, Lim SS, Mallhi K, Marsh RA, Murguia-Favela L, Parikh S, Touzot F, Cowan MJ, Dvorak CC, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson TR, Kang EM, Malech HL, Segre JA, Bryant CE, Holland SM, Falcone EL. Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease. J Allergy Clin Immunol. 2023 Dec;152(6):1619-1633.e11. doi: 10.1016/j.jaci.2023.07.022. Epub 2023 Sep 1.

  PMID: 37659505 DERIVED

• Leiding JW, Arnold DE, Parikh S, Logan B, Marsh RA, Griffith LM, Wu R, Kidd S, Mallhi K, Chellapandian D, Si Lim SJ, Grunebaum E, Falcone EL, Murguia-Favela L, Grossman D, Prasad VK, Heimall JR, Touzot F, Burroughs LM, Bleesing J, Kapoor N, Dara J, Williams O, Kapadia M, Oshrine BR, Bednarski JJ, Rayes A, Chong H, Cuvelier GDE, Forbes Satter LR, Martinez C, Vander Lugt MT, Yu LC, Chandrakasan S, Joshi A, Prockop SE, Davila Saldana BJ, Aquino V, Broglie LA, Ebens CL, Madden LM, DeSantes K, Milner J, Rangarajan HG, Shah AJ, Gillio AP, Knutsen AP, Miller HK, Moore TB, Graham P, Bauchat A, Bunin NJ, Teira P, Petrovic A, Chandra S, Abdel-Azim H, Dorsey MJ, Birbrayer O, Cowan MJ, Dvorak CC, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson TR, Malech HL, Kang EM. Genotype, oxidase status, and preceding infection or autoinflammation do not affect allogeneic HCT outcomes for CGD. Blood. 2023 Dec 14;142(24):2105-2118. doi: 10.1182/blood.2022019586.

  PMID: 37562003 DERIVED

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Primary Immune Deficiency Treatment Consortium (PIDTC)
• Rare Diseases Clinical Research Network

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood, skin swabs and stool samples

MeSH Terms

Conditions

Granulomatous Disease, Chronic

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jennifer M. Puck, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Donald B. Kohn, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2014
• First Posted: March 10, 2014
• Study Start: June 1, 2014
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: September 2, 2021

Record last verified: 2021-09

Locations

US (39); CA (5)