A Study of Severe Combined Immunodeficiency Disorders

Overview

About this study

In this prospective natural history study, the aim is to identify variables contributing to best outcomes for hematopoietic cell tranplantation (HCT) or other treatment where applicable (enzyme replacement or gene therapy), which is life-saving therapy for children with SCID, leaky SCID, Omenn syndrome and reticular dysgenesis.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria

Stratum A
- Classic Severe Combined Immunodeficiency patients
- Intention to treat with allogeneic hematopoietic cell transplant (HCT)
- 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
- Intention to treat with HCT
For 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)
  - ≥ 10% and ≤ 30% of lower limit of normal T cell function (as measured by response to PHA)
  - Absent proliferative responses to candida and tetanus toxoid antigens (post vaccination or exposure), with expression of HLA by flow/serology
For 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)
For 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 Treatment Patients
- Intention to treat with PEG-ADA or gene transfer with autologous modified cells
- 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

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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status	Contact
Rochester, Minn. Mayo Clinic principal investigator Avni Joshi, M.D., M.S.	Closed for enrollment	Contact information: Joni Amundson amundson.joni@mayo.edu

Mayo Clinic Location

Status

Contact

Rochester, Minn.

Mayo Clinic principal investigator

Avni Joshi, M.D., M.S.

Closed for enrollment

Contact information:

Joni Amundson

amundson.joni@mayo.edu

More information

Publications

Allogeneic hematopoietic cell transplantation (HCT) has been used for 40 years to ameliorate or cure primary immune deficiency (PID) diseases, including severe combined immunodeficiency (SCID) and non-SCID PID. There is a critical need for evaluation of the North American experience of different HCT approaches for these diseases to identify best practices and plan future investigative clinical trials. Our survey of incidence and prevalence of PID in North American practice sites indicates that such studies are feasible. A conference of experts in HCT treatment of PID has recommended (1) a comprehensive cross-sectional and retrospective analysis of HCT survivors with SCID; (2) a prospective study of patients with SCID receiving HCT, with comparable baseline and follow-up testing across participating centers; (3) a pilot study of newborn screening for SCID to identify affected infants before compromise by infection; and (4) studies of the natural history of disease in patients who do or do not receive HCT for the non-SCID diseases of Wiskott-Aldrich syndrome and chronic granulomatous disease. To accomplish these goals, collaboration by a consortium of institutions in North America is proposed. Participation of immunologists and HCT physicians having interest in PID and experts in laboratory methods, clinical outcomes assessment, databases, and analysis will be required for the success of these studies. Read More on PubMed

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