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Summary

at San Francisco, California and other locations
study started
estimated completion:

Description

Summary

Individuals 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.

Official Title

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

Details

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 future. Participants are then followed according to a schedule set out by the study protocol after the procedure. There are no experimental therapies on this study.

The study plans to enroll over 200 participants with SCID. By studying new participants undergoing treatment for SCID, the goal is to learn more about: (1) outcomes from the treatment of SCID in the modern era of medicine (2) what factors lead to the best long-term outcomes, such as best donor, conditioning regimen, timing of transplant, etc., and (3) what impact newborn screening and the early diagnosis of SCID has had on the long-term outcomes following BMT or gene therapy. Information is also being gathered on how and when the immune system recovers after BMT, quality of life for long-term survivors, and about whether children develop normally after treatment.

This natural history study is the largest coordinated prospective study of participants with SCID ever performed. Information that we will learn, both now and in the future, will help doctors and other health professionals to better treat children with SCID.

Keywords

SCID Leaky SCID Omenn Syndrome Reticular Dysgenesis ADA Deficiency XSCID SCID disorders natural history study Severe Combined Immunodeficiency

Eligibility

You can join if…

  • Stratum A, 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(Classic SCID):

  • Absence or very low number (<300 /µL) of CD3+T cells, AND
  • No or very low (<10% of lower limit of normal) T cell function (as measured by response to phytohemagglutinin (HLA) 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 not detected;
  • AND either one or both of the following with rule-out of MHC Class I and II non- expression by flow cytometry (or histology):
  • <30% of lower limit of normal T cell function (as measured by response to PHA),OR
  • Absent or <10% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens (post vaccination or exposure), with expression of HLA by flow/serology.
  • AND either one or both of the following:
  • ≥80% of CD3+ or CD4+ T cells are CD45RO+ (at ≤2 years of age), OR
  • Genetic abnormality for SCID.
  • AND does not meet criteria for Omenn Syndrome.

Omenn Syndrome:

  • Generalized skin rash;
  • Maternal lymphocytes not detected;

--Note: If maternal engraftment was not assessed and ruled out, the patient is not eligible as Omenn Syndrome.

  • ≥80% of CD3+ or CD4+ T cells are CD45RO+ ( ≤ 2 years of age)
  • Absent or low (< 30% lower limit of normal) T cell proliferation to antigens

NOTE: If proliferation to antigen was not performed, but at least 4 of the following 8 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 < 30% of lower limit of normal or SI < 20
  • *Mutation to SCID causing gene.

Reticular Dysgenesis:

  • <300/µL number of T cells (CD3 < 300 / µL);
  • None or <10% lower limit of normal PHA proliferation;
  • Severe neutropenia (absolute neutrophil count < 200 /µL); AND
  • One or more of the following:
  • Sensori-neural deafness OR
  • Deficiency of marrow granulopoiesis on bone marrow examination OR
  • A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified.

Stratum C, SCID with Non-HCT Treatments. Subjects 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; or
  • X-linked SCID with intention to treat with gene transfer. Note: For subjects with presumed ADA SCID, T cell studies MUST be obtained prior to enzyme replacement therapy with PEG-ADA ERT or blood transfusion.

You CAN'T join if...

-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 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, transcobalamin deficiency.
  • The majority of subjects with deficiency defects such as nucleoside phosphorylase,ZAP70, CD40 ligand , NEMO, XLP, cartilage hair hypoplasia or ataxia telangiectasia.
  • Case by case exceptions for Stratum B for subject(s) with one of these deficiency defects, as determined by the PID SCID Review Panel.

Locations

  • University of California San Francisco Children's Hospital accepting new patients
    San Francisco, California, 94143-1278, United States
  • Stanford University accepting new patients
    Stanford, California, 94305, United States
  • Children's Hospital Los Angeles accepting new patients
    Los Angeles, California, 90027, United States
  • University of California, Los Angeles accepting new patients
    Los Angeles, California, 90095-1752, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Links
National Institute of Allergy and Infectious Diseases (NIAID)
Primary Immune Deficiency Treatment Consortium (PIDTC)
ID
NCT01186913
Lead Scientists
Chris Dvorak
Morton J. Cowan
Study Type
Observational
Last Updated
October 10, 2017
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