Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
1007 participants
OBSERVATIONAL
2011-05-15
2023-08-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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COHORT
RETROSPECTIVE
Study Groups
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Stratum A -Typical SCID
Typical Severe Combined Immunodeficiency (SCID), Adenosine Deaminase-Deficient ADA SCID, and X-linked SCID (XSCID) who received a transplant
No interventions assigned to this group
Stratum B - Atypical SCID
Leaky SCID, Omenn Syndrome, and Reticular Dysgenesis who received a transplant
No interventions assigned to this group
Stratum C - SCID w/Non-HCT Treatments
SCID who received Polyethylene Glycol -Adenosine Deaminase Enzyme Replacement Therapy (PEG-ADA ERT) or gene therapy
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
* Individuals with Severe Combined Immune Deficiency (SCID) diagnosis who:
--were treated at a location participating in this consortium from 1968 until present, and
--are not enrolled in RDCRN PIDTC-6901 (ClinicalTrials.gov ID: NCT01186913).
* Subjects who received HCT/GT/ERT prior to the present date are eligible for the retrospective study. The enrollment criteria for subjects who died prior to definitive therapy are the same as for Strata A, B and C.
Stratum A, Typical SCID:
* Absence or very low number of T cells (CD3 T cells \< 300/microliter), and no or very low T cell function (\< 10% of lower limit of normal) as measured by response to phytohemagglutinin (PHA) or cells of maternal origin present.
* If maternal cells are present but the patient does not meet criteria for very low T cell function as defined, the assigned reviewers for the potential subject, and if necessary, the full PID-SCID RP will review the laboratory report to determine if criteria of maternal engraftment are met for Protocol 6902.
* Laboratory report of testing for maternal engraftment is required, for evaluation by the PID-SCID RP.
Stratum B, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis:
Individuals who meet the following criteria are eligible for enrollment into Stratum B of the study:
Leaky SCID-
* Maternal lymphocytes tested for and not detected and,
* Either one or both of the following (a,b):
a) \< 50% of lower limit of normal T cell function (as measured by response to PHA OR \< 50% of lower limit of normal T cell function as measured by response to CD3/CD28 antibody, b) Absent or \< 30% lower limit of normal proliferative responses to candida and tetanus toxoid antigens postvaccination or exposure,
* AND at least one of the following (a through e):
1. Reduced number of CD3 T cells,
2. \> 80% of CD3+ or CD4 T cells are CD45RO+,
* AND/OR \>80% of CD3+ or CD4+ T cells are,CD62L negative,
* AND/OR \>50% of CD3+ or CD4+ T cells express HLA-DR (at \< 4 years of age),
* AND/OR are oligoclonal T cells. c) Hypomorphic mutation in IL2RG in a male, or homozygous hypomorphic mutation or compound heterozygosity with at least one hypomorphic mutation in an autosomal SCID-causing gene.
d) Low TRECs and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal.
e) Functional testing in vitro supporting impaired, but not absent, activity of the mutant protein,
* AND does not meet criteria for Omenn Syndrome,
* AND does not have known selective loss of lymphocytes, Ataxia- Telangiectasia, or congenital heart defect associated with lymphopenia, unless a SCID genotype is also present.
Omenn Syndrome (OS):
* Generalized skin rash,
* Maternal engraftment tested for and not detected,
* Absent or low (up to 30% of normal) T cell proliferation to antigens to which the patient has been exposed.
* If the proliferation to antigen was not performed, but at least 4 of the following 10 supportive criteria, at least one of which must be among those marked with an asterisk (\*) are present, the patient is eligible: hepatomegaly; splenomegaly; lymphadenopathy; elevated IgE; elevated absolute eosinophil count; \*oligoclonal T cells measured by CDR3 length or flow cytometry \>80% of CD4+ T cells are CD45RO+ ;\*proliferation to PHA is reduced \<50% of lower limit of normal or SI \<30; \*proliferative response in mixed leukocyte reaction is reduced to increment cpm \< 20% or SI \<20; hypomorphic mutation to SCID causing gene; low TRECs and/or percentage of CD 4+/ RA+/CD31+; or CD4+/RA+/CD62L+ cells below the lower limit of normal.
Reticular Dysgenesis (RD):
* Absence or very low number of T cells (CD3 T cells \<300/microliter),
* No or very low (\<10% of lower limit of normal) T cell function (as measured by response to phytohemagglutinin (PHA),
* Severe congenital neutropenia (absolute neutrophil count \<200/microliter),
* AND at least one of the following:
* Sensorineural deafness and/or absence of granulopoiesis at bone marrow examination and/or a deleterious AK2 mutation,
* absence of granulopoiesis on bone marrow examination; a pathogenic mutation in the adenylate kinase 2 (AK2) gene identified.
Stratum C, SCID with Non-HCT Treatments:
-Individuals who meet the following criteria and were treated with PEG-ADA or gene therapy with autologous modified cells are eligible for enrollment into Stratum C (SCID with non-HCT treatments) of the study-
\- Any SCID patient previously treated with a thymus transplant (includes intention to treat with HCT, as well as PEG-ADA ERT or gene therapy).
Strata A, B, and C (Part 2 - Cross-Sectional Study):
* MHC Class I and MHC Class II antigen deficiency are excluded,
* Metabolic conditions that imitate SCID or related disorders such as folate transporter deficiency, severe zinc deficiency, transcobalamin deficiency.
Exclusion Criteria
* Lack of appropriate testing to rule out HIV infection after 1997 (p24 antigen or more sensitive) or other cause of secondary immunodeficiency,
* Presence of DiGeorge syndrome,
ALL
No
Sponsors
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Primary Immune Deficiency Treatment Consortium (PIDTC)
OTHER
National Center for Advancing Translational Sciences (NCATS)
NIH
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Elie Haddad, MD, PhD
Role: STUDY_CHAIR
University of Montréal, CHU Sainte-Justine
Richard J. O'Reilly, MD
Role: STUDY_CHAIR
Memorial Sloan Kettering Cancer Center
Morton J. Cowan, MD
Role: STUDY_CHAIR
University of California, San Francisco
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Mattel Children's Hospital UCLA: Division of Pediatric Hematology/Oncology
Los Angeles, California, United States
Lucile Salter Packard Children's Hospital at Stanford
Palo Alto, California, United States
University of California San Francisco Children's Hospital
San Francisco, California, United States
Children's Hospital Denver:Center for Cancer and Blood Disorders
Denver, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Children's Healthcare of Atlanta/Emory University School of Medicine
Atlanta, Georgia, United States
Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Children's Hospital/Louisiana State University Health Sciences Center
New Orleans, Louisiana, United States
NIH Clinical Center Genetic Immunotherapy Section
Bethesda, Maryland, United States
Children's Hospital Boston
Boston, Massachusetts, United States
University of Michigan Health System
Ann Arbor, Michigan, United States
University of Minnesota Medical Center
Minneapolis, Minnesota, United States
SSM Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States
Washington University St Louis Children's Hospital
St Louis, Missouri, United States
Hackensack University Medical Center: Department of Pediatrics
Hackensack, New Jersey, United States
Memorial Sloan-Kettering Cancer Center: Department of Pediatrics
New York, New York, United States
Duke University Medical Center: Department of Pediatrics, Division of Allergy/Immunology
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Oregon Health & Science University: Pediatric Hematology/Oncology
Portland, Oregon, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
University of Texas Southwestern Medical Center Dallas
Dallas, Texas, United States
Texas Children's Hospital
Houston, Texas, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
Primary Children's Medical Center/University of Utah
Salt Lake City, Utah, United States
Fred Hutchinson Cancer Research Center: Clinical Research Division and Pediatric Stem Cell Transplantation Center
Seattle, Washington, United States
University of Wisconsin/ American Family Children's Hospital
Madison, Wisconsin, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Alberta Children's Hospital
Calgary, Alberta, Canada
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
Cancer Care Manitoba
Winnipeg, Manitoba, Canada
The Hospital for Sick Children (SickKids)
Toronto, Ontario, Canada
CHU St. Justine
Montreal, Quebec, Canada
Countries
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References
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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.
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.
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.
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.
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.
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.
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.
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.
Kohn DB, Hershfield MS, Puck JM, Aiuti A, Blincoe A, Gaspar HB, Notarangelo LD, Grunebaum E. Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency. J Allergy Clin Immunol. 2019 Mar;143(3):852-863. doi: 10.1016/j.jaci.2018.08.024. Epub 2018 Sep 5.
Miggelbrink AM, Logan BR, Buckley RH, Parrott RE, Dvorak CC, Kapoor N, Abdel-Azim H, Prockop SE, Shyr D, Decaluwe H, Hanson IC, Gillio A, Davila Saldana BJ, Eibel H, Hopkins G, Walter JE, Whangbo JS, Kohn DB, Puck JM, Cowan MJ, Griffith LM, Haddad E, O'Reilly RJ, Notarangelo LD, Pai SY. B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation. Blood. 2018 Jun 28;131(26):2967-2977. doi: 10.1182/blood-2017-10-809822. Epub 2018 May 4.
Haddad E, Logan BR, Griffith LM, Buckley RH, Parrott RE, Prockop SE, Small TN, Chaisson J, Dvorak CC, Murnane M, Kapoor N, Abdel-Azim H, Hanson IC, Martinez C, Bleesing JJH, Chandra S, Smith AR, Cavanaugh ME, Jyonouchi S, Sullivan KE, Burroughs L, Skoda-Smith S, Haight AE, Tumlin AG, Quigg TC, Taylor C, Davila Saldana BJ, Keller MD, Seroogy CM, Desantes KB, Petrovic A, Leiding JW, Shyr DC, Decaluwe H, Teira P, Gillio AP, Knutsen AP, Moore TB, Kletzel M, Craddock JA, Aquino V, Davis JH, Yu LC, Cuvelier GDE, Bednarski JJ, Goldman FD, Kang EM, Shereck E, Porteus MH, Connelly JA, Fleisher TA, Malech HL, Shearer WT, Szabolcs P, Thakar MS, Vander Lugt MT, Heimall J, Yin Z, Pulsipher MA, Pai SY, Kohn DB, Puck JM, Cowan MJ, O'Reilly RJ, Notarangelo LD. SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery. Blood. 2018 Oct 25;132(17):1737-1749. doi: 10.1182/blood-2018-03-840702. Epub 2018 Aug 28.
Dvorak CC, Haddad E, Buckley RH, Cowan MJ, Logan B, Griffith LM, Kohn DB, Pai SY, Notarangelo L, Shearer W, Prockop S, Kapoor N, Heimall J, Chaudhury S, Shyr D, Chandra S, Cuvelier G, Moore T, Shenoy S, Goldman F, Smith AR, Sunkersett G, Vander Lugt M, Caywood E, Quigg T, Torgerson T, Chandrakasan S, Craddock J, Davila Saldana BJ, Gillio A, Shereck E, Aquino V, DeSantes K, Knutsen A, Thakar M, Yu L, Puck JM. The genetic landscape of severe combined immunodeficiency in the United States and Canada in the current era (2010-2018). J Allergy Clin Immunol. 2019 Jan;143(1):405-407. doi: 10.1016/j.jaci.2018.08.027. Epub 2018 Sep 5.
Cuvelier GDE, Logan BR, Prockop SE, Buckley RH, Kuo CY, Griffith LM, Liu X, Yip A, Hershfield MS, Ayoub PG, Moore TB, Dorsey MJ, O'Reilly RJ, Kapoor N, Pai SY, Kapadia M, Ebens CL, Forbes Satter LR, Burroughs LM, Petrovic A, Chellapandian D, Heimall J, Shyr DC, Rayes A, Bednarski JJ, Chandra S, Chandrakasan S, Gillio AP, Madden L, Quigg TC, Caywood EH, Davila Saldana BJ, DeSantes K, Eissa H, Goldman FD, Rozmus J, Shah AJ, Vander Lugt MT, Thakar MS, Parrott RE, Martinez C, Leiding JW, Torgerson TR, Pulsipher MA, Notarangelo LD, Cowan MJ, Dvorak CC, Haddad E, Puck JM, Kohn DB. Outcomes following treatment for ADA-deficient severe combined immunodeficiency: a report from the PIDTC. Blood. 2022 Aug 18;140(7):685-705. doi: 10.1182/blood.2022016196.
Related Links
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Primary Immune Deficiency Treatment Consortium (PIDTC)
Division of Allergy, Immunology, and Transplantation (DAIT)
National Institute of Allergy and Infectious Diseases (NIAID)
National Center for Advancing Translational Sciences (NCATS)
Other Identifiers
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DAIT RDCRN PIDTC-6902
Identifier Type: -
Identifier Source: org_study_id