Patients Treated for SCID (1968-Present)

November 9, 2020 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Retrospective and Cross-Sectional Analysis of Patients Treated for SCID Since January 1,1968 (RDCRN PIDTC-6902)

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.

Study Overview

Status

Enrolling by invitation

Conditions

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 Type

Observational

Enrollment (Anticipated)

1007

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Individuals with diagnosis of SCID or SCID variants treated at Participating Consortium Centers from 1968-Present

Description

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):

    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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Retrospective Study - Part 1
Time Frame: 1, 5, 10, 20, >20 years
Overall survival
1, 5, 10, 20, >20 years
Cross-Sectional Study - Part 2
Time Frame: 2 to > 20 years
Full immune reconstitution
2 to > 20 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Retrospective Study Part 1
Time Frame: 1 year to > 20 years
Immune reconstitution and clinical outcomes
1 year to > 20 years
Retrospective Study - Part 1
Time Frame: 3 months to >20 years
Engraftment
3 months to >20 years
Cross-Sectional Study - Part 2
Time Frame: 2 to >20 years
Current state of lineage-specific chimerism
2 to >20 years
Cross-Sectional Study - Part 2
Time Frame: 2 to >20 years
Current status of health
2 to >20 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

National Center for Advancing Translational Sciences (NCATS)
Primary Immune Deficiency Treatment Consortium (PIDTC)

Investigators

  • Study Chair: Elie Haddad, MD, PhD, University of Montréal, CHU Sainte-Justine
  • Study Chair: Richard J. O'Reilly, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 15, 2011

Primary Completion (ANTICIPATED)

August 1, 2023

Study Completion (ANTICIPATED)

August 1, 2023

Study Registration Dates

First Submitted

April 29, 2011

First Submitted That Met QC Criteria

April 29, 2011

First Posted (ESTIMATE)

May 2, 2011

Study Record Updates

Last Update Posted (ACTUAL)

November 12, 2020

Last Update Submitted That Met QC Criteria

November 9, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAIT RDCRN PIDTC-6902

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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