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Patients Treated for SCID (1968-Present)

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Enrolling by invitation
CT.gov ID
NCT01346150
Collaborator
Primary Immune Deficiency Treatment Consortium (PIDTC) (Other), National Center for Advancing Translational Science (NCATS) (NIH)
1,007
Enrollment
36
Locations
146.6
Anticipated Duration (Months)
28
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Individuals with a past diagnosis of severe combined immune deficiency (including many cases of "leaky SCID", Omenn syndrome, and reticular dysgenesis) who have undergone blood and marrow transplant, gene therapy, or enzyme replacement in the past may be eligible for this study. The purpose of study is to look backwards at what has already been done in the. Over 800 patients with SCID are expected to be enrolled, making this one of the largest studies ever to describe outcomes for patients with SCID treated at many different hospitals around North America.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    One of the most important components of this study is the "cross sectional" aspect. Patients who have received their treatments (BMT, gene therapy, enzyme replacement) many years ago are asked to come back to the hospital where they were treated. During this visit, additional research bloodwork is drawn, and information is gathered regarding long-term transplant outcomes such as infections, graft-versus-host disease, autoimmune diseases, and quality of life. This will allow PIDTC researchers to better understand long-term outcomes from procedures that occurred many years ago (sometimes over 30 years ago). This will help researchers to best design new treatments and clinical trials in the future for children with SCID.

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    1007 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)
    Actual Study Start Date :
    May 15, 2011
    Anticipated Primary Completion Date :
    Aug 1, 2023
    Anticipated Study Completion Date :
    Aug 1, 2023

    Arms and Interventions

    Arm Intervention/Treatment
    Stratum A -Typical SCID

    Typical Severe Combined Immunodeficiency (SCID), Adenosine Deaminase-Deficient ADA SCID, and X-linked SCID (XSCID) who received a transplant
    Stratum B - Atypical SCID

    Leaky SCID, Omenn Syndrome, and Reticular Dysgenesis who received a transplant
    Stratum C - SCID w/Non-HCT Treatments

    SCID who received Polyethylene Glycol -Adenosine Deaminase Enzyme Replacement Therapy (PEG-ADA ERT) or gene therapy

    Outcome Measures

    Primary Outcome Measures

    1. Retrospective Study - Part 1 [1, 5, 10, 20, >20 years]

      Overall survival

    2. Cross-Sectional Study - Part 2 [2 to > 20 years]

      Full immune reconstitution

    Secondary Outcome Measures

    1. Retrospective Study Part 1 [1 year to > 20 years]

      Immune reconstitution and clinical outcomes

    2. Retrospective Study - Part 1 [3 months to >20 years]

      Engraftment

    3. Cross-Sectional Study - Part 2 [2 to >20 years]

      Current state of lineage-specific chimerism

    4. Cross-Sectional Study - Part 2 [2 to >20 years]

      Current status of health

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 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):

    1. < 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.

    1. Low TRECs and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal.

    2. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35233
    2 Children's Hospital Los Angeles Los Angeles California United States 90027
    3 Mattel Children's Hospital UCLA: Division of Pediatric Hematology/Oncology Los Angeles California United States 90095-1752
    4 Lucile Salter Packard Children's Hospital at Stanford Palo Alto California United States 94305
    5 University of California San Francisco Children's Hospital San Francisco California United States 94143-1278
    6 Children's Hospital Denver:Center for Cancer and Blood Disorders Denver Colorado United States 80220
    7 Children's National Medical Center Washington District of Columbia United States 20010-2970
    8 Johns Hopkins All Children's Hospital Saint Petersburg Florida United States 33701
    9 Children's Healthcare of Atlanta/Emory University School of Medicine Atlanta Georgia United States 30322
    10 Lurie Children's Hospital of Chicago Chicago Illinois United States 60614
    11 Children's Hospital/Louisiana State University Health Sciences Center New Orleans Louisiana United States 70118
    12 NIH Clinical Center Genetic Immunotherapy Section Bethesda Maryland United States 20892
    13 Children's Hospital Boston Boston Massachusetts United States 02115
    14 University of Michigan Health System Ann Arbor Michigan United States 48109
    15 University of Minnesota Medical Center Minneapolis Minnesota United States 55455
    16 SSM Cardinal Glennon Children's Medical Center Saint Louis Missouri United States 63104
    17 Washington University St Louis Children's Hospital Saint Louis Missouri United States 63110
    18 Hackensack University Medical Center: Department of Pediatrics Hackensack New Jersey United States 07601
    19 Memorial Sloan-Kettering Cancer Center: Department of Pediatrics New York New York United States 10065
    20 Duke University Medical Center: Department of Pediatrics, Division of Allergy/Immunology Durham North Carolina United States 27710
    21 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    22 Oregon Health & Science University: Pediatric Hematology/Oncology Portland Oregon United States 97239-3098
    23 The Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    24 St. Jude Children's Research Hospital Memphis Tennessee United States 38105
    25 University of Texas Southwestern Medical Center Dallas Dallas Texas United States 75235
    26 Texas Children's Hospital Houston Texas United States 77030-2399
    27 Methodist Children's Hospital of South Texas San Antonio Texas United States 78229
    28 Primary Children's Medical Center/University of Utah Salt Lake City Utah United States 84113
    29 Fred Hutchinson Cancer Research Center: Clinical Research Division and Pediatric Stem Cell Transplantation Center Seattle Washington United States 98101
    30 University of Wisconsin/ American Family Children's Hospital Madison Wisconsin United States 53705-2275
    31 Medical College of Wisconsin Milwaukee Wisconsin United States 53226-4874
    32 Alberta Children's Hospital Calgary Alberta Canada T3B 6A8
    33 British Columbia Children's Hospital Vancouver British Columbia Canada V6H 3V4
    34 Cancer Care Manitoba Winnipeg Manitoba Canada R3E 0V9
    35 The Hospital for Sick Children (SickKids) Toronto Ontario Canada M5G 1XB
    36 CHU St. Justine Montréal Quebec Canada H3T 1C5

    Sponsors and Collaborators

    • National Institute of Allergy and Infectious Diseases (NIAID)
    • Primary Immune Deficiency Treatment Consortium (PIDTC)
    • National Center for Advancing Translational Science (NCATS)

    Investigators

    • Study Chair: Elie Haddad, MD, PhD, University of MontrĂ©al, CHU Sainte-Justine
    • Study Chair: Richard J. O'Reilly, MD, Memorial Sloan Kettering Cancer Center
    • Study Chair: Morton J. Cowan, MD, University of California, San Francisco

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    National Institute of Allergy and Infectious Diseases (NIAID)
    ClinicalTrials.gov Identifier:
    NCT01346150
    Other Study ID Numbers:
    • DAIT RDCRN PIDTC-6902
    First Posted:
    May 2, 2011
    Last Update Posted:
    Nov 12, 2020
    Last Verified:
    Nov 1, 2020
    Additional relevant MeSH terms:
    Severe Combined Immunodeficiency

    Study Results

    No Results Posted as of Nov 12, 2020