Natural History Study of SCID Disorders

Study ID
DAIT RDCRN PIDTC-6901

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)

Contact
Gevel Jackson
214-456-7194
gevel.jackson@childrens.com

Principal Investigator
Victor Aquino, M.D.

Official Title

A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children With SCID Disorders (RDCRN PIDTC-6901)

Brief Overview


People with Primary Immune Deficiency (PID) may develop severe, life-threatening infections
as a result of inherited defects in the genes that normally instruct blood-forming cells to
develop and to fight infections. PID diseases include Severe Combined Immune Deficiency
(SCID), leaky SCID, Omenn syndrome (OS), and Reticular Dysgenesis (RD). PIDs may be treated
by transplantation of bone marrow stem cells from a healthy person or, in some cases, by
enzyme replacement or by gene therapy. Patients with SCID were among the first to receive
bone marrow stem cell (also called hematopoietic cells) transplantation (HCT) more than 40
years ago, and HCT is the standard treatment today for this group of diseases. Since PID
diseases are rare, there are not enough patients at any single center to determine the full
range of causes, natural history, or best methods of treatment. For this research study many
PID centers across North America have organized into the Primary Immune Deficiency Treatment
Consortium (PIDTC) to pool their experience and study PIDs together. The overall goal of
this study is the prospective evaluation of children with SCID and related disorders who are
treated under a variety of protocols at participating institutions. The study aims to
identify variables contributing to the best outcomes for HCT.

Participant Eligibility


Inclusion Criteria:

- Stratum A, Classic SCID Patients 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 - Absence or very low number (< 300 / ul) of T
cells, AND no or very low (<10% of lower limit of normal) T cell function (as
measured by response to phytohemagglutinin OR T cells of maternal origin present, but
with <10% of lower limit of normal T cell function (as measured by response to PHA)

Stratum B, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis Patients who meet the
following criteria and the intention is to treat with HCT are eligible for enrollment into
Stratum B-

Leaky SCID:

- <1000 / ul T cell number at < age 2 years; < 800 / ul T cell number at age 2 through
< 4 years; < 600 / ul at > 4 years; and maternal lymphocytes not detected, AND either
one or both of the following with rule-out of MHC Class I or II non-expression by
flow cytometry (or histology):

1. ≥ 10% and ≤ 30% of lower limit of normal T cell function (as measured by
response to PHA), b) Absent proliferative responses to candida and tetanus
toxoid antigens (post vaccination or exposure), with expression of HLA by
flow/serology

Omenn Syndrome:

- Generalized skin rash

- Maternal lymphocytes not detected

- Absent or low (< 30% lower limit of normal) T cell proliferation to antigens

- > 80% of CD4 T cells are CD45RO+ (< 2 years of age)

Reticular Dysgenesis:

- < 300 / ul T cell number

- None or < 10% lower limit of normal PHA proliferation

- Sensori-neural deafness

- Severe neutropenia (< 200 / uL and unresponsive to G-CSF) and deficiency of marrow
granulopoiesis unless there is known adenylate kinase 2 (AK2) pathogenic mutation(s)
identified

Stratum C, SCID with Non-HCT Treatments Patients who meet the following criteria and the
intention is to treat with PEG-ADA or gene transfer with autologous modified cells are
eligible for enrollment into Stratum C:

- ADA Deficient SCID with intention to treat with PEG-ADA

- ADA Deficient SCID with intention to treat with gene transfer

- X-linked SCID with intention to treat with gene transfer

Exclusion Criteria:

- Patients who meet any one or more of the following exclusion criteria are
disqualified from enrollment in Strata A, B, or C of the study:

- Presence of an HIV infection (by PCR) 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 specifically excluded.

- Metabolic conditions that imitate SCID or related disorders such as folate
transporter deficiency, severe zinc deficiency, transcobalamin deficiency