Natural History Study of SCID Disorders

NCT01186913 | Enrolling By Invitation

• 1 other identifier: DAIT RDCRN PIDTC-6901
• Study Type: observational
• Target: 690
• Locations: 2 countries
• Sites: 44

Brief Summary

This study is a prospective evaluation of children with Severe Combined Immune Deficiency (SCID) who are treated under a variety of protocols used by participating institutions. In order to determine the patient, recipient and transplant-related variables that are most important in determining outcome, study investigators will uniformly collect pre-, post- and peri-transplant (or other treatment) information on all children enrolled into this study. Children will be divided into three strata:

• Stratum A: Typical SCID with virtual absence of autologous T cells and poor T cell function
• Stratum B: Atypical SCID (leaky SCID, Omenn syndrome and reticular dysgenesis with limited T cell diversity or number and reduced function), and
• Stratum C: ADA deficient SCID and XSCID patients receiving alternative therapy including PEG-ADA ERT or gene therapy. Each Group/Cohort Stratum will be analyzed separately.

Conditions

Severe Combined Immunodeficiency (SCID); Leaky SCID; Omenn Syndrome; Reticular Dysgenesis; ADA SCID; XSCID

Keywords

Severe Combined Immunodeficiency (SCID); natural history study; SCID treatment

Outcome Measures

Primary Outcomes (4)

• Overall Survival (OS) at Month 6 Post HCT

  Assess the overall survival (OS) for participants after hematopoietic stem cell transplantation (HCT) for treatment of Severe Combined Immunodeficiency (SCID). The time to this event is the time from HCT to death or last follow-up (whichever occurs first). All participants will be followed for a minimum of 6 months from HCT. Overall survival will be estimated at 6 months.

  Month 6 Post HCT

• Overall Survival (OS) at Year 2 Post HCT

  Assess the overall survival (OS) for participants after hematopoietic stem cell transplantation (HCT) for treatment of Severe Combined Immunodeficiency (SCID). The time to this event is the time from HCT to death or last follow-up (whichever occurs first). All participants will be followed for a minimum of 6 months from HCT. Overall survival will be estimated at 2 years.

  Year 2 Post HCT

• Overall Survival (OS) at Year 5 Post HCT

  Assess the overall survival (OS) for participants after hematopoietic stem cell transplantation (HCT) for treatment of Severe Combined Immunodeficiency (SCID). The time to this event is the time from HCT to death or last follow-up (whichever occurs first). All participants will be followed for a minimum of 6 months from HCT. Overall survival will be estimated at 5 years.

  Year 5 Post HCT

• Overall Survival (OS) at Year 8 Post HCT

  Assess the overall survival (OS) for participants after hematopoietic stem cell transplantation (HCT) for treatment of Severe Combined Immunodeficiency (SCID). The time to this event is the time from HCT to death or last follow-up (whichever occurs first). All participants will be followed for a minimum of 6 months from HCT. Overall survival will be estimated at 8 years.

  Year 8 Post HCT

Secondary Outcomes (17)

• T Cell Reconstitution by Stratum-Month 6, Year 2, Year 5 and Year 8 Post-SCID Treatment

  From SCID Treatment (HCT, ERT or GT) to Month 6, Year 2, Year 5 and Year 8 Post-SCID Treatment

• B Cell Reconstitution by Stratum-Month 6, Year 2, Year 5 and Year 8 Post-SCID Treatment

  From SCID Treatment (HCT, ERT or GT) to Month 6, Year 2, Year 5 and Year 8 Post-SCID Treatment

• Engraftment at Day 100, Month 6, Year 2, Year 5 and Year 8 Post-HCT

  From HCT to Month 6, Year 2, Year 5 and Year 8 Post-HCT

• Time to Resolution of Infections Diagnosed Prior to HCT

  Through study completion, up to 8 years post-HCT

• Incidence of New Infections Post-HCT

  From HCT to Day 100, Month 6, Year 1, Year 2, Year 5, and Year 8 post-HCT

Study Arms (3)

Stratum A: Typical SCID +HCT

Stratum A: Typical Severe Combined Immunodeficiency (SCID) treated with HCT therapy. Participants with typical (formerly referred to as classic) SCID + allogeneic hematopoietic stem cell transplantation (HCT) therapy according to standard of care, per local protocol.

Stratum B: Atypical SCID +HCT

Stratum B: Atypical Severe Combined Immunodeficiency (SCID) treated with HCT therapy. Participants with leaky SCID, Omenn syndrome, or Reticular Dysgenesis (RS) + allogeneic hematopoietic stem cell transplantation (HCT) therapy according to standard of care, per local protocol.

Stratum C:SCID +Non-HCT

Stratum C: Severe Combined Immunodeficiency (SCID) who receive alternative therapy per standard of care, non-standard care and/or investigational. This stratum includes: * Adenosine Deaminase-Deficient SCID (ADA Deficient SCID) with intention to treat with Polyethylene Glycol -Adenosine Deaminase Enzyme Replacement Therapy (PEG-ADA ERT) * ADA Deficient SCID with intention to treat with gene therapy * X-linked SCID (XSCID) with intention to treat with gene therapy * Any individual with SCID previously treated with a thymus transplant (includes intention to treat with HCT, as well as PEG-ADA ERT or gene therapy)

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

Patients with SCID spectrum disorders that have undergone diagnostic workup per local center practice and referred for enrollment in this natural history study at one of the participating institutions (clinical research site locations).

You may qualify if:

• 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
• T cells of maternal origin present.
• Stratum B: Leaky SCID, Omenn Syndrome, Reticular Dysgenesis-
• Subjects who meet the following criteria and the intention is to treat with HCT are eligible for enrollment into Stratum B:
• 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 response to anti-CD3/CD28 antibody
• b.) Absent or \<30% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens
• AND at least two of the following (a through e):
• a.) Reduced number of CD3 T cells
• age ≤2 years: \<1500/microliter
• age \>2 years and ≤4 years: \<800/microliter
• age \>4 years: \<600/microliter

You may not qualify if:

• Presence of an Human Immunodeficiency Virus (HIV) infection (by PCR) or other cause of secondary immunodeficiency
• Presence of DiGeorge syndrome
• MHC Class I and MHC Class II antigen deficiency, and
• Metabolic conditions that imitate SCID or related disorders such as folate transporter deficiency, severe zinc deficiency or transcobalamin deficiency.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Primary Immune Deficiency Treatment Consortium (PIDTC): collaborator
• Office of Rare Diseases (ORD): collaborator
• National Center for Advancing Translational Sciences (NCATS): 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

University of California, Los Angeles

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 San Francisco Children's Hospital

San Francisco, California, 94143-1278, United States

Location

Children's Hospital Denver

Denver, Colorado, 80220, United States

Location

Alfred I. duPont Hospital for Children/Nemours

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

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

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta/Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

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

Chicago, Illinois, 60614, United States

Location

Children's Hospital/Louisiana State University Health Sciences Center

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, 55905, United States

Location

Cardinal Glennon Children's Medical Center

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

University Hospitals-Rainbow Babies and Children's Hospital

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/Children's of Dallas

Dallas, Texas, 75390-9263, United States

Location

Texas Children's Hospital

Houston, Texas, 77030-2399, 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

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-4874, 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 Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (13)

• 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

• 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

• 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

• 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

• 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

• 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

• 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.

  PMID: 30193840 RESULT

• Rayes A, Logan BR, Liu X, Dara J, Buckley RH, Oved JH, Kapoor N, Kapadia M, Chandra S, Martinez CA, Bunin N, Chandrakasan S, Chen K, Bednarski JJ, Haines HL, Eissa H, Talano JM, Keller MD, Ebens CL, Chaudhury S, Shereck EB, Aquino VM, Knutsen AP, Alexander JL, Gillio AP, Chellapandian D, Shah AJ, Miller HK, Vander Lugt MT, Seroogy CM, Dorsey MJ, Mousallem T, Parrott RE, O'Reilly RJ, Aguayo-Hiraldo PI, Prockop SE, Davila Saldana BJ, Thakar MS, Burroughs LM, Torgerson TR, Leiding JW, Marsh RA, Griffith LM, Pulsipher MA, Kohn DB, Notarangelo LD, Cowan MJ, Puck JM, Cuvelier GDE, Heimall J, Haddad E, Pai SY, Dvorak CC. Outcomes Following Matched Sibling Donor Transplantation for Severe Combined Immunodeficiency: A Report from the PIDTC. Blood Adv. 2025 Nov 25:bloodadvances.2025016812. doi: 10.1182/bloodadvances.2025016812. Online ahead of print.

  PMID: 41289158 DERIVED

• 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.

  PMID: 35671392 DERIVED

• Dorsey MJ, Wright NAM, Chaimowitz NS, Davila Saldana BJ, Miller H, Keller MD, Thakar MS, Shah AJ, Abu-Arja R, Andolina J, Aquino V, Barnum JL, Bednarski JJ, Bhatia M, Bonilla FA, Butte MJ, Bunin NJ, Chandra S, Chaudhury S, Chen K, Chong H, Cuvelier GDE, Dalal J, DeFelice ML, DeSantes KB, Forbes LR, Gillio A, Goldman F, Joshi AY, Kapoor N, Knutsen AP, Kobrynski L, Lieberman JA, Leiding JW, Oshrine B, Patel KP, Prockop S, Quigg TC, Quinones R, Schultz KR, Seroogy C, Shyr D, Siegel S, Smith AR, Torgerson TR, Vander Lugt MT, Yu LC, Cowan MJ, Buckley RH, Dvorak CC, Griffith LM, Haddad E, Kohn DB, Logan B, Notarangelo LD, Pai SY, Puck J, Pulsipher MA, Heimall J. Infections in Infants with SCID: Isolation, Infection Screening, and Prophylaxis in PIDTC Centers. J Clin Immunol. 2021 Jan;41(1):38-50. doi: 10.1007/s10875-020-00865-9. Epub 2020 Oct 2.

  PMID: 33006109 DERIVED

• Heimall J, Logan BR, Cowan MJ, Notarangelo LD, Griffith LM, Puck JM, Kohn DB, Pulsipher MA, Parikh S, Martinez C, Kapoor N, O'Reilly R, Boyer M, Pai SY, Goldman F, Burroughs L, Chandra S, Kletzel M, Thakar M, Connelly J, Cuvelier G, Davila Saldana BJ, Shereck E, Knutsen A, Sullivan KE, DeSantes K, Gillio A, Haddad E, Petrovic A, Quigg T, Smith AR, Stenger E, Yin Z, Shearer WT, Fleisher T, Buckley RH, Dvorak CC. Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study. Blood. 2017 Dec 21;130(25):2718-2727. doi: 10.1182/blood-2017-05-781849. Epub 2017 Oct 11.

  PMID: 29021228 DERIVED

Related Links

• Primary Immune Deficiency Treatment Consortium (PIDTC) featured highlights
• Division of Allergy, Immunology, and Transplantation (DAIT)
• National Institute of Allergy and Infectious Diseases (NIAID)
• Rare Diseases Clinical Research Network (RDCRN)
• National Center for Advancing Translational Science (NCATS)

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood samples, tissue, and bone marrow samples collected during participation in this study.

MeSH Terms

Conditions

Severe Combined Immunodeficiency; Reticular dysgenesis; Severe combined immunodeficiency due to adenosine deaminase deficiency; X-Linked Combined Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Genetic Diseases, X-Linked

Study Officials

• Christopher C. Dvorak, MD

  UCSF Children's Hospital

  PRINCIPAL INVESTIGATOR

• Morton J. Cowan, MD

  UCSF Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 20, 2010
• First Posted: August 23, 2010
• Study Start: September 2, 2010
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 10, 2020

Record last verified: 2020-11

Locations

CA (5); US (39)