Natural History Study of SCID Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01186913
Recruitment Status : Recruiting
First Posted : August 23, 2010
Last Update Posted : October 12, 2017
Office of Rare Diseases (ORD)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
Individuals with Primary Immune Deficiency (PID) may develop severe, life-threatening infections as a result of inherited defects in the genes that normally instruct blood-forming cells to develop and to fight infections. PID diseases include Severe Combined Immune Deficiency (SCID), leaky SCID, Omenn syndrome (OS), and Reticular Dysgenesis (RD). PIDs may be treated by transplantation of bone marrow stem cells from a healthy person or, in some cases, by enzyme replacement or by gene therapy. Patients with SCID were among the first to receive bone marrow stem cell (also called hematopoietic cells) transplantation (HCT) more than 40 years ago, and HCT is the standard treatment today for this group of diseases. Since PID diseases are rare, there are not enough patients at any single center to determine the full range of causes, natural history, or best methods of treatment. For this research study many PID centers across North America have organized into the Primary Immune Deficiency Treatment Consortium (PIDTC) to pool their experience and study PIDs together. The overall goal of this study is the prospective evaluation of children with SCID and related disorders who are treated under a variety of protocols at participating institutions. The study aims to identify variables contributing to the best outcomes for HCT.

Condition or disease
SCID Leaky SCID Omenn Syndrome Reticular Dysgenesis ADA Deficiency XSCID

Detailed Description:

This study follows participants with SCID prospectively, meaning the study enrolls participants where there is a plan to receive a blood and marrow transplant, enzyme therapy, or gene therapy in the future. Participants are then followed according to a schedule set out by the study protocol after the procedure. There are no experimental therapies on this study.

The study plans to enroll over 200 participants with SCID. By studying new participants undergoing treatment for SCID, the goal is to learn more about: (1) outcomes from the treatment of SCID in the modern era of medicine (2) what factors lead to the best long-term outcomes, such as best donor, conditioning regimen, timing of transplant, etc., and (3) what impact newborn screening and the early diagnosis of SCID has had on the long-term outcomes following BMT or gene therapy. Information is also being gathered on how and when the immune system recovers after BMT, quality of life for long-term survivors, and about whether children develop normally after treatment.

This natural history study is the largest coordinated prospective study of participants with SCID ever performed. Information that we will learn, both now and in the future, will help doctors and other health professionals to better treat children with SCID.

Study Type : Observational
Estimated Enrollment : 209 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children With SCID Disorders (RDCRN PIDTC-6901)
Study Start Date : August 2010
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Classic SCID (Stratum A)
Patients with classic SCID after allogeneic hematopoietic stem cell transplantation
Leaky SCID, Omenn syndrome, or RS (Stratum B)
Patients with leaky SCID, Omenn syndrome, or Reticular Dysgenesis (RS) after allogeneic hematopoietic stem cell transplantation
ADA Deficiency or XSCID treated with PEG-ADA (Stratum C)
Patients with ADA Deficiency or XSCID who are treated with PEG-ADA (patients with ADA Deficiency) or patients who are treated with gene therapy (ADA Deficiency or XSCID)

Primary Outcome Measures :
  1. Overall survival following HCT [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Full T cell reconstitution [ Time Frame: 6 months post HCT ]
  2. Full T cell reconstitution [ Time Frame: 12 months post HCT ]
  3. Full T cell reconstitution [ Time Frame: 24 months post HCT ]
  4. Full B cell reconstitution [ Time Frame: 12 months post HCT ]
  5. Full B cell reconstitution [ Time Frame: 24 months post HCT ]
  6. Engraftment [ Time Frame: 100 days ]
  7. Engraftment [ Time Frame: 6 months ]
  8. Engraftment [ Time Frame: 12 months ]
  9. Engraftment [ Time Frame: 24 months ]
  10. Infections [ Time Frame: 24 months ]
  11. Growth and Nutrition [ Time Frame: 24 months ]
  12. Graft versus Host Disease [ Time Frame: 24 months ]
  13. Occurrence of autoimmunity requiring treatment [ Time Frame: Throughout the study ]
  14. Neurodevelopment/Neurocognition [ Time Frame: 24 months ]
  15. Other complications of HCT needing treatment [ Time Frame: Throughout the study ]
  16. Quality of Life [ Time Frame: 24 months ]

Biospecimen Retention:   Samples With DNA
Peripheral blood samples, tissue, and bone marrow samples collected during participation in this study.

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with diagnosis of SCID or SCID variants treated at Consortium Centers from 1968-2010

Inclusion Criteria:

  • Stratum A, Classic SCID.

Subjects who meet the following inclusion criteria and the intention is to treat with allogeneic hematopoietic cell transplant (HCT) are eligible for enrollment into Stratum A (Classic SCID):

  • Absence or very low number (<300 /µL) of CD3+T cells, AND
  • No or very low (<10% of lower limit of normal) T cell function (as measured by response to phytohemagglutinin (HLA) 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 not detected;
  • AND either one or both of the following with rule-out of MHC Class I and II non- expression by flow cytometry (or histology):

    • <30% of lower limit of normal T cell function (as measured by response to PHA), OR
    • Absent or <10% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens (post vaccination or exposure), with expression of HLA by flow/serology.
  • AND either one or both of the following:

    • ≥80% of CD3+ or CD4+ T cells are CD45RO+ (at ≤2 years of age), OR
    • Genetic abnormality for SCID.
  • AND does not meet criteria for Omenn Syndrome.

Omenn Syndrome:

  • Generalized skin rash;
  • Maternal lymphocytes not detected;

    --Note: If maternal engraftment was not assessed and ruled out, the patient is not eligible as Omenn Syndrome.

  • ≥80% of CD3+ or CD4+ T cells are CD45RO+ ( ≤ 2 years of age)
  • Absent or low (< 30% lower limit of normal) T cell proliferation to antigens

NOTE: If proliferation to antigen was not performed, but at least 4 of the following 8 supportive criteria, at least one of which must be among those marked with an asterisk (*) below are present, the subject is eligible as Omenn Syndrome:

  • Hepatomegaly
  • Splenomegaly
  • Lymphadenopathy
  • Elevated IgE
  • Elevated absolute eosinophil count
  • *Oligoclonal T cells measured by CDR3 length or flow cytometry
  • *Proliferation to PHA is reduced < 30% of lower limit of normal or SI < 20
  • *Mutation to SCID causing gene.

Reticular Dysgenesis:

  • <300/µL number of T cells (CD3 < 300 / µL);
  • None or <10% lower limit of normal PHA proliferation;
  • Severe neutropenia (absolute neutrophil count < 200 /µL); AND
  • One or more of the following:

    • Sensori-neural deafness OR
    • Deficiency of marrow granulopoiesis on bone marrow examination OR
    • A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified.

Stratum C, SCID with Non-HCT Treatments. Subjects who meet the following criteria and the intention is to treat with PEG-ADA or gene transfer with autologous modified cells are eligible for enrollment into Stratum C:

  • ADA Deficient SCID with intention to treat with PEG-ADA;
  • ADA Deficient SCID with intention to treat with gene transfer; or
  • X-linked SCID with intention to treat with gene transfer. Note: For subjects with presumed ADA SCID, T cell studies MUST be obtained prior to enzyme replacement therapy with PEG-ADA ERT or blood transfusion.

Exclusion Criteria:

-Subjects who meet any of the following exclusion criteria are disqualified from enrollment in Strata A, B, or C of the study:

  • Presence of an 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, transcobalamin deficiency.
  • The majority of subjects with deficiency defects such as nucleoside phosphorylase ,ZAP70, CD40 ligand , NEMO, XLP, cartilage hair hypoplasia or ataxia telangiectasia.

    • Case by case exceptions for Stratum B for subject(s) with one of these deficiency defects, as determined by the PID SCID Review Panel.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01186913

  Hide Study Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Fredrick Goldman, MD    205-939-5855   
Principal Investigator: Fredrick Goldman, MD         
United States, Arizona
Phoenix Children's Hospital Recruiting
Phoenix, Arizona, United States, 85016
Contact: Holly Miller, MD    602-933-0920   
Principal Investigator: Holly Miller, MD         
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Renna Killen, RN    323-361-2217   
Principal Investigator: Neena Kapoor, MD         
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095-1752
Contact: Theodore Moore, MD    310-825-6708   
Principal Investigator: Theodore Moore, MD         
University of California San Francisco Children's Hospital Recruiting
San Francisco, California, United States, 94143-1278
Contact: Elizabeth Dunn, MA    415-502-0203   
Principal Investigator: Morton Cowan, MD         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Katja Weinacht, MD    617-919-8775   
Principal Investigator: Katja Weinacht, MD         
United States, Colorado
Children's Hospital Denver Recruiting
Denver, Colorado, United States, 80220
Contact: John Craddock, MD    720-777-3328   
Principal Investigator: John Craddock, MD         
United States, Delaware
Alfred I. duPont Hospital for Children/Nemours Recruiting
Wilmington, Delaware, United States, 19803
Contact: Emi Caywood, MD    302-651-5500   
Principal Investigator: Emy Caywood, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, D.C., District of Columbia, United States, 20010-2970
Contact: Blachy Dávila Dávila Saldaña, MD    (202)476-4561   
Principal Investigator: Blachy Dávila Saldaña, MD         
United States, Florida
All Children's Hospital, St. Petersburg FL Recruiting
Saint Petersburg, Florida, United States, 33701
Contact: Benjamin Oshrine, MD    727-767-4176   
Principal Investigator: Benjamin Oshrine, MD         
United States, Georgia
Children's Healthcare of Atlanta/Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact: Elizabeth Stenger, MD    404-785-1272   
Principal Investigator: Elizabeth Stenger, MD         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60614
Contact: Morris Kletzel, MD    773-880-4598   
Principal Investigator: Morris Kletzel, MD         
United States, Louisiana
Children's Hospital/Louisiana State University Health Sciences Center Recruiting
New Orleans, Louisiana, United States, 70118
Contact: Lolie Yu, MD    504-896-9740   
Principal Investigator: Lolie Yu, MD         
United States, Maryland
NIH Clinical Center Genetic Immunotherapy Section Recruiting
Bethesda, Maryland, United States, 20892
Contact: Harry Malech, MD    301-480-6916   
Principal Investigator: Harry Malech, MD         
United States, Massachusetts
Children's Hospital Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Sung-Yun Pai, MD    617-919-2508   
Principal Investigator: Sung-Yun Pai, MD         
United States, Michigan
University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Mark Vander Lugt, MD    734-936-9814   
Principal Investigator: Mark Vander Lugt, MD         
United States, Minnesota
University of Minnesota Medical Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Angie Smith, MD    612-626-2778   
Principal Investigator: Angie Smith, MD         
Mayo Clinic Hospital Recruiting
Rochester, Minnesota, United States, 55905
Contact: Richard Bram, MD    507-284-2695   
Principal Investigator: Richard Bram, MD         
United States, Missouri
Cardinal Glennon Children's Medical Center Recruiting
Saint Louis, Missouri, United States, 63104
Contact: Wendy Sanders, RN    314-268-2700 ext 3513   
Principal Investigator: Alan Knutsen, MD         
Washington University St Louis Children's Hospital Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Shalini Shenoy, MD    314-454-6018   
Principal Investigator: Shalini Shenoy, MD         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Alfred Gillio, MD    201-996-5645   
Principal Investigator: Alfred Gillio, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Monica Bhatia, MD    212-305-9138   
Principal Investigator: Monica Bhatia, MD         
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Richard J O'Reilly    212-639-5957   
Principal Investigator: Richard J O'Reilly, MD         
University of Rochester Medical Center/ Golisano Children's Hospital Recruiting
Rochester, New York, United States, 14642
Contact: Jeffrey Andolina, MD    585-276-3229   
Principal Investigator: Jeffrey Andolina, MD         
New York Medical College, Maria Fareri Children's Hospital Recruiting
Valhalla, New York, United States, 10595
Contact: Allyson Flower, MD    914-493-7997   
Principal Investigator: Allyson Flower, MD         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Rebecca Buckley, MD    919-684-2922   
Principal Investigator: Rebecca Buckley, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Sharat Chandra, MD    513-636-5917   
Principal Investigator: Sharat Chandra, MD         
Rainbow Babies/ University Hospitals Case Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jignesh Dalal, MD    216-844-3345   
Principal Investigator: Jignesh Dalal, MD         
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Rolla Abu-arja, MD    614-722-3582   
Principal Investigator: Rolla Abu-Arja, MD         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Evan Shereck, MD    503-494-0829   
Principal Investigator: Evan Shereck, MD         
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jennifer Heimall, MD    215-590-2549   
Principal Investigator: Jennifer Heimall, MD         
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Jessie Barnum, MD    412-692-7035   
Principal Investigator: Jessie Barnum, MD         
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Ewelina Mamcarz, MD    901-595-8343   
Principal Investigator: Ewelina Mamcarz, MD         
United States, Texas
University of Texas Southwestern Medical Center/Children's of Dallas Recruiting
Dallas, Texas, United States, 75390-9263
Contact: Victor Aquino, MD    214-648-8800   
Principal Investigator: Victor Aquino, MD         
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030-2399
Contact: Chivon McMullen-Jackson, RN, BSN    832-824-1339   
Principal Investigator: William Shearer, MD         
Methodist Children's Hospital of South Texas/Texas Transplant Institute Recruiting
San Antonio, Texas, United States, 78229
Contact: Troy Quigg, MD    210-575-7348   
Principal Investigator: Troy Quigg, MD         
United States, Utah
Primary Children's Medical Center/University of Utah Recruiting
Salt Lake City, Utah, United States, 84113
Contact: David Shyr, MD    801-662-4736   
Principal Investigator: David Shyr, MD         
United States, Washington
Seattle Children's Research Institute Recruiting
Seattle, Washington, United States, 98101
Contact: Lauri M Burroughs, MD    206-667-2396   
Principal Investigator: Lauri M Burroughs, MD         
United States, Wisconsin
University of Wisconsin/ American Family Children's Hospital Recruiting
Madison, Wisconsin, United States, 53705-2275
Contact: Kenneth DeSantes, MD    608-263-8563   
Principal Investigator: Kenneth DeSantes         
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226-4874
Contact: Monica S Thakar, MD    414-266-6848   
Principal Investigator: Monica S Thakar, MD         
Canada, Alberta
Alberta Children's Hospital Not yet recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Nicola Wright, MD    403-955-3035   
Principal Investigator: Nicola Wright, MD         
Canada, British Columbia
British Columbia Children's Hospital Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Jeffrey Davis, MD    604-875-3577   
Principal Investigator: Jeffrey Davis, MD         
Canada, Manitoba
Cancer Care Manitoba Recruiting
Winnipeg, Manitoba, Canada, R3E 0V9
Contact: Geoff Cuvelier, MD    204-787-8689   
Principal Investigator: Geoff Cuvelier, MD         
Canada, Ontario
The Hospital for Sick Children Not yet recruiting
Toronto, Ontario, Canada, M5G 1XB
Contact: Eyal Grunebaum, MD    416-813-7654   
Principal Investigator: Eyal Grunebaum, MD         
Canada, Quebec
CHU St. Justine Recruiting
Montreal, Quebec, Canada, H3T 1C5
Contact: Elie Haddad, MD    514-345-4931 ext 6217   
Principal Investigator: Elie Haddad, MD         
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Office of Rare Diseases (ORD)
Principal Investigator: Chris Dvorak, MD UCSF Children's Hospital
Principal Investigator: Morton J. Cowan, MD UCSF Children's Hospital

Additional Information:
Publications of Results:

Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT01186913     History of Changes
Obsolete Identifiers: NCT02108067
Other Study ID Numbers: DAIT RDCRN PIDTC-6901
First Posted: August 23, 2010    Key Record Dates
Last Update Posted: October 12, 2017
Last Verified: October 2017

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
SCID disorders
natural history study

Additional relevant MeSH terms:
Severe Combined Immunodeficiency
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases