Trial Search Results

Natural History Study of SCID Disorders

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 the patient, recipient and transplant-related variables that are most important in determining outcome, study investigators will uniformly collect pre-, post- and peri-transplant (or other treatment) information on all children enrolled into this study.

Children will be divided into three strata:

- Stratum A: Typical SCID with virtual absence of autologous T cells and poor T cell function

- Stratum B: Atypical SCID (leaky SCID, Omenn syndrome and reticular dysgenesis with limited T cell diversity or number and reduced function), and

- Stratum C: ADA deficient SCID and XSCID patients receiving alternative therapy including PEG-ADA ERT or gene therapy.

Each Group/Cohort Stratum will be analyzed separately.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator: Primary Immune Deficiency Treatment Consortium (PIDTC)

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.

Ages Eligible for Study

N/A - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Matthew Porteus, MD
650-725-6520
Recruiting