Status:
ENROLLING_BY_INVITATION
Natural History Study of SCID Disorders
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborating Sponsors:
Primary Immune Deficiency Treatment Consortium (PIDTC)
Office of Rare Diseases (ORD)
Conditions:
Severe Combined Immunodeficiency (SCID)
Leaky SCID
Eligibility:
All Genders
Brief Summary
This study is a prospective evaluation of children with Severe Combined Immune Deficiency (SCID) who are treated under a variety of protocols used by participating institutions. In order to determine ...
Detailed Description
This study follows participants with SCID prospectively, meaning the study enrolls participants where there is a plan to receive a blood and marrow transplant, enzyme therapy, or gene therapy in the f...
Eligibility Criteria
Inclusion
- 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
- 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.
Key Trial Info
Start Date :
September 2 2010
Trial Type :
OBSERVATIONAL
Allocation :
ESTIMATED
End Date :
September 1 2028
Estimated Enrollment :
690 Patients enrolled
Trial Details
Trial ID
NCT01186913
Start Date
September 2 2010
End Date
September 1 2028
Last Update
November 10 2020
Active Locations (44)
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1
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
2
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
3
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
4
University of California, Los Angeles
Los Angeles, California, United States, 90095-1752