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Patients Treated for SCID (1968-Present)

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ClinicalTrials.gov Identifier: NCT01346150
Recruitment Status : Recruiting
First Posted : May 2, 2011
Last Update Posted : November 9, 2017
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
Primary Immune Deficiency Treatment Consortium
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
People 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. Researchers will collect information on your general health, psychological and developmental health, and the current status of your immune system to help better define future approaches to PID treatments.

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

Study Type : Observational
Estimated Enrollment : 1146 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: A Retrospective and Cross-Sectional Analysis of Patients Treated for SCID Since January 1,1968 (RDCRN PIDTC-6902)
Study Start Date : May 2011
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019


Group/Cohort
Stratum A
SCID, ADA-SCID, and XSCID who received a transplant
Stratum B
Leaky SCID, Omenn Syndrome, and Reticular Dysgenesis who received a transplant
Stratum C
SCID who received PEG ADA or gene therapy



Primary Outcome Measures :
  1. Retrospective Study - Part 1 [ Time Frame: 1, 5, 10, 20, >20 years ]
    Overall survival

  2. Cross-Sectional Study - Part 2 [ Time Frame: 2 to > 20 years ]
    Full immune reconstitution


Secondary Outcome Measures :
  1. Retrospective Study Part 1 [ Time Frame: 1 year to > 20 years ]
    Immune reconstitution and clinical outcomes

  2. Retrospective Study - Part 1 [ Time Frame: 3 months to >20 years ]
    Engraftment

  3. Cross-Sectional Study - Part 2 [ Time Frame: 2 to >20 years ]
    Current state of lineage-specific chimerism

  4. Cross-Sectional Study - Part 2 [ Time Frame: 2 to >20 years ]
    Current status of health


Biospecimen Retention:   Samples With DNA
Biospecimens may include blood, other tissues (e.g., buccal swab or brushing), and/or bone marrow.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

Strata A, B, and C (Part 1 - Retrospective Study)-

  • 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:

  • Individuals who meet the following inclusion criteria and who received HCT are eligible for enrollment into Stratum A (Classic SCID) of the study:

    • 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):

Patient inclusion criteria for the cross sectional study: Eligibility for Strata A, B and C are the same as for the retrospective study except that all the patients in the cross-sectional study are currently surviving and are at least 2 years post the most recent class of therapy.

Exclusion Criteria:

Parts 1 and 2 - Retrospective and Cross-Sectional Studies -

  • 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,
  • Most patients with other PIDs such as nucleoside phosphorylase deficiency, ZAP70 deficiency, CD40 ligand deficiency, NEMO deficiency, XLP, cartilage hair hypoplasia or ataxia telangiectasia will not meet the inclusion criteria for Stratum A, B, or C above; however, a patient with one of the above may meet the inclusion criteria for Stratum B and if so will be included-

    • 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.

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 ClinicalTrials.gov identifier (NCT number): NCT01346150


  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Fredrick Goldman, MD    205-939-5855    fgoldman@peds.uab.edu   
Principal Investigator: Fredrick Goldman, MD         
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Renna Killen, RN    323-361-2217    rkillen@chla.usc.edu   
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    TBMoore@mednet.ucla.edu   
Principal Investigator: Theodore Moore, MD         
University of California San Francisco Children's Hospital Recruiting
San Francisco, California, United States, 94143-1278
Contact: Elizabeth Dunn    415-476-4860    DunnE@peds.ucsf.edu   
Principal Investigator: Morton Cowan, MD         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Katja Weinacht, MD    650-725-6520    kgw1@stanford.edu   
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    John.Craddock@childrenscolorado.org   
Principal Investigator: John Craddock, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010-2970
Contact: Blachy Saldaña, MD    202-476-4561    Bjdavilas1@childrensnational.org   
Principal Investigator: Blachy 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    Boshrin1@jhmi.edu   
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    Elizabeth.Stenger@choa.org   
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    MKletzel16@northwestern.edu   
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    lyu@lsuhsc.edu   
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    hmalech@mail.nih.gov   
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    sung-yun.pai@childrens.harvard.edu   
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    737-936-9814    marvande@med.umich.edu   
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    smith719@umn.edu   
Principal Investigator: Angie Smith, 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    Wendy_Sanders@ssmhc.com   
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    shenoy@wustl.edu   
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    AGillio@HackensackUMC.org   
Principal Investigator: Alfred Gillio, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Richard J O'Reilly, MD    212-639-5957    oreillyr@mskc.org   
Principal Investigator: Richard J O'Reilly, MD         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Rebecca Buckley, MD    919-684-2922    buck1003@mc.duke.edu   
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    Sharat.Chandra@cchmc.org   
Principal Investigator: Sharat Chandra, MD         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Evan Shereck, MD    503-494-0829    Shereck@ohsu.edu   
Principal Investigator: Evan Shereck, MD         
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kathleen Sullivan, MD, PhD    215-590-1697    sullivak@mail.med.upenn.edu   
Principal Investigator: Kathleen Sullivan, MD, PhD         
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Ewelina Mamcarz, MD    901-595-8343    ewelina.mamcarz@stjude.org   
Principal Investigator: Ewelina Mamcarz, MD         
United States, Texas
University of Texas Southwestern Medical Center/Children's of Dallas Recruiting
Dallas, Texas, United States, 75235
Contact: Victor Aquino, MD    214-648-8800    victor.aquino@utsouthwestern.edu   
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    cdmcmull@texaschildrens.org   
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    Troy.Quigg@MHShealth.com   
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    David.Shyr@hsc.utah.edu   
Principal Investigator: David Shyr, MD         
United States, Washington
University of Washington & Seattle Children's Hospital/ Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98101
Contact: Lauri M. Burroughs, MD    206-667-2396    lburroug@fhcrc.org   
Principal Investigator: Lauri 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    kbdesantes@pediatrics.wisc.edu   
Principal Investigator: Kenneth DeSantes, MD         
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226-4874
Contact: Monica Thakar, MD    414-266-6840    mthakar@mcw.edu   
Principal Investigator: Monica Thakar, MD         
Canada, Alberta
Alberta Children's Hospital Not yet recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Nicola Wright, MD    403-955-3035    Nicola.Wright@albertahealthservices.ca   
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    jdavis@cw.bc.ca   
Principal Investigator: Jeffrey Davis, MD         
Canada, Manitoba
Cancer Care Manitoba Recruiting
Winnipeg, Manitoba, Canada, R3E 0V9
Contact: Marlis Schroeder, MD    (204) 787-4372    marlis.schroeder@cancercare.mb.ca   
Principal Investigator: Marlis Schroeder, MD         
Canada, Ontario
The Hospital for Sick Children Not yet recruiting
Toronto, Ontario, Canada, M5G 1XB
Contact: Eyal Grunebaum, MD    416-813-7654    Eyal.Grunebaum@sickkids.ca   
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    elie.haddad@umontreal.ca   
Principal Investigator: Elie Haddad, MD         
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Rare Diseases Clinical Research Network
Primary Immune Deficiency Treatment Consortium
Investigators
Principal Investigator: Morton J Cowan, MD UCSF Children's Hospital
Principal Investigator: Elie Haddad, MD St. Justine's Hospital

Additional Information:
Publications of Results:

Other Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01346150     History of Changes
Other Study ID Numbers: DAIT RDCRN PIDTC-6902
First Posted: May 2, 2011    Key Record Dates
Last Update Posted: November 9, 2017
Last Verified: November 2017

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