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This study observes the course of disease in people with severe combined immunodeficiency (SCID) and related immune disorders, including patients treated with stem cell transplant, PEG-ADA enzyme therapy, or gene therapy. It includes patients with diagnoses such as typical SCID, leaky SCID, Omenn syndrome, reticular dysgenesis, and ADA- or IL2RG-related SCID. It is being carried out as a study with no assigned phase and is enrolling participants by invitation.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
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Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
Inclusion Criteria:
Stratum A: Typical SCID (formerly referred to as 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 (Typical 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
* 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 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 response to anti-CD3/CD28 antibody
* b.) Absent or \<30% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens
* AND at least two of the following (a through e):
* a.) Reduced number of CD3 T cells
* age ≤2 years: \<1500/microliter
* age \>2 years and ≤4 years: \<800/microliter
* age \>4 years: \<600/microliter
* b.) ≥80% of CD3+ or CD4+ T cells that 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 ≥1 hypomorphic mutation in an autosomal SCID-causing gene
* d.) Low T Cell Receptor Excision Circles (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.
Omenn Syndrome:
* Generalized skin rash
* Maternal lymphocytes tested for and not detected;
--Note: If maternal engraftment was not assessed and ruled out, the subject is not eligible as Omenn Syndrome.
* ≥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 \<2 years of age);
* Absent or low (\< 30% lower limit of normal) T cell proliferation response to antigens (Candida, tetanus) to which the subject has been exposed
NOTE: If proliferation to antigen was not performed, but at least 4 of the following 9 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 \<50% of lower limit of normal or SI \<30
* \*Hypomorphic mutation in a SCID causing gene
* Low TRECS and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal.
Reticular Dysgenesis:
* Absence or very low number of T cells (CD3 \<300/µL
* No or very low (\<10% lower limit of normal) T cell response to PHA
* Severe neutropenia (absolute neutrophil count \< 200 /µL) AND
* ≥2 of the following (a,b,c):
* a.) Sensori-neural deafness
* b.) Deficiency of marrow granulopoiesis on bone marrow examination
* c.) A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified.
Stratum C:
Subjects who meet the following criteria and the intention is to treat with therapy other than allogeneic HCT, primarily PEG-ADA ERT or gene therapy with autologous modified (gene transduced) cells, are eligible for enrollment into
Stratum C:
* ADA Deficient SCID with intention to treat with PEG-ADA ERT
* ADA Deficient SCID with intention to treat with gene therapy
* X-linked SCID with intention to treat with gene therapy
* Any SCID patient previously treated with a thymus transplant (includes intention to treat with HCT, as well as PEG-ADA ERT or gene therapy)
* Any SCID patient who received therapy for SCID deemed "non-standard" or "investigational", including in utero procedures.
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 Human Immunodeficiency Virus (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 or transcobalamin deficiency.