Granulomatous Disease, Chronic Clinical Trial
Official title:
Analysis of Patients Treated for Chronic Granulomatous Disease Since January 1, 1995
Verified date | September 2021 |
Source | National Institute of Allergy and Infectious Diseases (NIAID) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
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.
Status | Enrolling by invitation |
Enrollment | 1480 |
Est. completion date | November 2021 |
Est. primary completion date | November 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A and older |
Eligibility | Inclusion Criteria: - Participant Inclusion Criteria (Part 1 - Longitudinal Analysis) - CGD Patients Undergoing Transplant 1995 to Present with Birth Year In or After 1988 1. 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 - A family history consistent with either X-linked or autosomal recessive CGD In cases where either functional assay (A) or history (B) is equivocal, one or more of the following may be used to confirm a diagnosis of CGD: C. Absent or significantly reduced in expression or abnormal size of any of the 5 phox components (gp91 phox, p47 phox, p22 phox, p67phox, and p40phox) of NADPH oxidase, by either: - Western blot - Northern blot OR D. Mutation in a gene encoding one of the 5 phox components (gp91 phox, p47 phox, p22 phox, p67 phox, and p40 phox) of NADPH oxidase that is predictive of a decreased or absent oxidative burst. (Nonsense, frameshift, or previously described missense mutation associated with CGD). Molecular Diagnosis is Desirable In addition, molecular diagnosis (gene sequencing and expression analysis) of CGD is desirable and should be performed when possible. 2. Further Characterization of Oxidase Level, Longitudinal Study, Prospective Cohort Patients who are to undergo transplantation during the study period must be further characterized as oxidase-null or oxidase positive by level of oxidase production by either: - DHR assay stimulation Index: where SI = 2.5 will be classified as oxidase-null CGD. Those with SI > 2.5 will be classified as oxidase positive CGD. A single validated test that is accepted by the PID-CGD Review Panel is adequate, but testing on two occasions for validation is desirable. OR - Ferricytochrome C reduction assay of granulocytes with O2 < 2.3 nmoles /106 cells/h classified as oxidase-null CGD. A single validated test that is accepted by the PID-CGD Review Panel is adequate, but testing on two occasions for validation is desirable. OR o Genetic sequencing reporting a mutation that is unequivocally associated to absent oxidase production. (e.g. null mutations) will be classified as oxidase-null CGD (See discussion in Appendix I for how family history, genotype and CGD mutation information will be applied to assigning patients lacking any quantitative oxidase activity measurements to residual oxidase-null or residual oxidase-positive groups). 3. Longitudinal Study, Retrospective Cohort Patients who have already been transplanted will be included regardless of whether further characterization by oxidase level (or genotype/mutation data) is possible or not. - Non-Transplanted CGD Patients with Birth Year In or After 1988 A non-transplant (conventional therapy) group of CGD subjects will be enrolled in the longitudinal study. The non-transplant subjects will be selected from the potentially eligible (retrospective) patient cohort with diagnosis of CGD treated with conventional non-transplant therapy. Participating sites will enter their entire retrospective cohort of CGD patients having birth year in or after 1988 into the registration cohort for this protocol. Baseline for both non-transplant subjects and HCT subjects for the purpose of comparing survival will be the year of birth. However, for non-transplant subjects, many of the detailed analyses such as infection and autoimmune complication rates will be assessed in the year preceding the date of last contact. - Participant Inclusion Criteria (Part 2 - Cross-Sectional Analysis) To participate in the Cross-Sectional Analysis, patients must have previously been enrolled into the Longitudinal Analysis of Protocol 6903. All transplanted subjects in the Cross-Sectional Analysis are surviving and shall have at least 3 years of follow-up post-transplant to be included. Non-transplanted CGD subjects will become eligible for consideration for the Cross-Sectional Analysis if they were eligible and enrolled in the retrospective cohort of the Longitudinal Analysis, and if/when they are > 3 years post-diagnosis of CGD. Provision of written informed consent will be required for inclusion in the Cross-Sectional Analysis. Exclusion Criteria: - Participant Exclusion Criteria (Longitudinal and Cross- Sectional Analyses) - 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: - The above exclusions pertain. - 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). |
Country | Name | City | State |
---|---|---|---|
Canada | Alberta Children's Hospital | Calgary | Alberta |
Canada | CHU St. Justine | Montreal | Quebec |
Canada | The Hospital for Sick Children | Toronto | Ontario |
Canada | British Columbia Children's Hospital | Vancouver | British Columbia |
Canada | Cancer Care Manitoba | Winnipeg | Manitoba |
United States | University of Michigan Health System | Ann Arbor | Michigan |
United States | Children's Healthcare of Atlanta, Emory University | Atlanta | Georgia |
United States | Children's Hospital Colorado | Aurora | Colorado |
United States | NIH Clinical Center Genetic Immunotherapy Section | Bethesda | Maryland |
United States | University of Alabama at Birmingham | Birmingham | Alabama |
United States | Children's Hospital Boston | Boston | Massachusetts |
United States | Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois |
United States | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio |
United States | Rainbow Babies/ University Hospitals Case Medical Center | Cleveland | Ohio |
United States | Nationwide Children's Hospital | Columbus | Ohio |
United States | University of Texas Southwestern Medical Center at Dallas | Dallas | Texas |
United States | Duke University | Durham | North Carolina |
United States | Hackensack University Medical Center | Hackensack | New Jersey |
United States | Texas Children's Hospital, Baylor College of Medicine | Houston | Texas |
United States | Children's Hospital Los Angeles | Los Angeles | California |
United States | UCLA | Los Angeles | California |
United States | University of Wisconsin/ American Family Children's Hospital | Madison | Wisconsin |
United States | St. Jude Children's Research Hospital | Memphis | Tennessee |
United States | Children's Hospital of Wisconsin-Milwaukee | Milwaukee | Wisconsin |
United States | University of Minnesota Medical Center | Minneapolis | Minnesota |
United States | Children's Hospital of New Orleans at LSUHSC | New Orleans | Louisiana |
United States | Memorial Sloan-kettering Cancer Center | New York | New York |
United States | Lucile Salter Packard Children's Hospital at Stanford | Palo Alto | California |
United States | The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
United States | Phoenix Children's Hospital | Phoenix | Arizona |
United States | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania |
United States | Oregon Health and Science University | Portland | Oregon |
United States | Mayo Clinic Hospital | Rochester | Minnesota |
United States | University of Rochester Medical Center/ Golisano Children's Hospital | Rochester | New York |
United States | Cardinal Glennon Children's Hospital/ St. Louis University | Saint Louis | Missouri |
United States | Washington University/ St.Louis Children's Hospital | Saint Louis | Missouri |
United States | Johns Hopkins All Children's Hospital - St. Petersburg, FL | Saint Petersburg | Florida |
United States | Primary Children's Medical Center/ University of Utah | Salt Lake City | Utah |
United States | Methodist Children's Hospital of South Texas/Texas Transplant Institute | San Antonio | Texas |
United States | University of California (UCSF) Benioff Children's Hospital | San Francisco | California |
United States | Seattle Children's Research Institute | Seattle | Washington |
United States | New York Medical College, Maria Fareri Children's Hospital | Valhalla | New York |
United States | Children's National Medical Center, Washington DC | Washington | District of Columbia |
United States | Alfred I. duPont Hospital for Children/Nemours | Wilmington | Delaware |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) | Primary Immune Deficiency Treatment Consortium (PIDTC), Rare Diseases Clinical Research Network |
United States, Canada,
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 — View Citation
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. — View Citation
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, Fle — View Citation
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. do — View Citation
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 defi — View Citation
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. — View Citation
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 — View Citation
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 — View Citation
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, — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Engraftment | Engraftment will be measures in whole blood using either fluorescent in situ hybridization (FISH) for sex chromosomes or short tandem repeat polymerase chain reaction (PCR) or (STRs) in whole blood. | an expected average of 3 years | |
Secondary | Quality of Life Measures | Age appropriate testing will be performed at the cross-sectional visit in patients surviving at least two years posttransplant:
Pediatrics quality of life (QL) Family Impact Module, Parent Report Peds QL Infant Scales Module (ages 1-24 months), Parent Report Peds QL Generic Core Scales for Toddlers (ages 2-4 yr), Parent Report Peds QL Generic Core Scales (ages 5-25 yr), Child/Parent Reports Peds QL Transplant Module Standard Form (SF)-36 (adult) Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT BMT) (adult) |
an expected average of 3 years | |
Secondary | Infections | CGD or transplant-related and transplant-related infection | an expected average of 3 years | |
Secondary | Autoimmune or inflammatory complications | - For HCT subjects, inflammation (inflammatory complications) includes chronic graft-versus-host disease (GVHD) | an expected average of 3 years |
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