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Patients Treated for SCID (1968-Present)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01346150
Recruitment Status : Enrolling by invitation
First Posted : May 2, 2011
Last Update Posted : November 12, 2020
Sponsor:
Collaborators:
Primary Immune Deficiency Treatment Consortium (PIDTC)
National Center for Advancing Translational Science (NCATS)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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
SCID ADA-SCID XSCID Leaky SCID Omenn Syndrome Reticular Dysgenesis

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.

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Study Type : Observational
Estimated 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
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 2023


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



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.


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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
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 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


Locations
Show Show 36 study locations
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
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Study Chair: Elie Haddad, MD, PhD University of Montréal, 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
Additional Information:
Publications of Results:
Haddad E, Logan BR, Griffith LM, Buckley RH, Parrott RE, Prockop SE, Small TN, Chaisson J, Dvorak CC, Murnane M, Kapoor N, Abdel-Azim H, Hanson IC, Martinez C, Bleesing JJH, Chandra S, Smith AR, Cavanaugh ME, Jyonouchi S, Sullivan KE, Burroughs L, Skoda-Smith S, Haight AE, Tumlin AG, Quigg TC, Taylor C, Dávila Saldaña BJ, Keller MD, Seroogy CM, Desantes KB, Petrovic A, Leiding JW, Shyr DC, Decaluwe H, Teira P, Gillio AP, Knutsen AP, Moore TB, Kletzel M, Craddock JA, Aquino V, Davis JH, Yu LC, Cuvelier GDE, Bednarski JJ, Goldman FD, Kang EM, Shereck E, Porteus MH, Connelly JA, Fleisher TA, Malech HL, Shearer WT, Szabolcs P, Thakar MS, Vander Lugt MT, Heimall J, Yin Z, Pulsipher MA, Pai SY, Kohn DB, Puck JM, Cowan MJ, O'Reilly RJ, Notarangelo LD. SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery. Blood. 2018 Oct 25;132(17):1737-1749. doi: 10.1182/blood-2018-03-840702. Epub 2018 Aug 28.

Other Publications:
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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    Key Record Dates
Last Update Posted: November 12, 2020
Last Verified: November 2020
Additional relevant MeSH terms:
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Severe Combined Immunodeficiency
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases