We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Natural History Study of SCID Disorders

This study is currently recruiting participants.
Verified October 2017 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01186913
First Posted: August 23, 2010
Last Update Posted: October 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Office of Rare Diseases (ORD)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
August 20, 2010
August 23, 2010
October 12, 2017
August 2010
August 2019   (Final data collection date for primary outcome measure)
Overall survival following HCT [ Time Frame: 4 years ]
Same as current
Complete list of historical versions of study NCT01186913 on ClinicalTrials.gov Archive Site
  • Full T cell reconstitution [ Time Frame: 6 months post HCT ]
  • Full T cell reconstitution [ Time Frame: 12 months post HCT ]
  • Full T cell reconstitution [ Time Frame: 24 months post HCT ]
  • Full B cell reconstitution [ Time Frame: 12 months post HCT ]
  • Full B cell reconstitution [ Time Frame: 24 months post HCT ]
  • Engraftment [ Time Frame: 100 days ]
  • Engraftment [ Time Frame: 6 months ]
  • Engraftment [ Time Frame: 12 months ]
  • Engraftment [ Time Frame: 24 months ]
  • Infections [ Time Frame: 24 months ]
  • Growth and Nutrition [ Time Frame: 24 months ]
  • Graft versus Host Disease [ Time Frame: 24 months ]
  • Occurrence of autoimmunity requiring treatment [ Time Frame: Throughout the study ]
  • Neurodevelopment/Neurocognition [ Time Frame: 24 months ]
  • Other complications of HCT needing treatment [ Time Frame: Throughout the study ]
  • Quality of Life [ Time Frame: 24 months ]
  • Full T cell reconstitution [ Time Frame: 6 months post HCT ]
  • Full T cell reconstitution [ Time Frame: 12 months post HCT ]
  • Full T cell reconstitution [ Time Frame: 24 months post HCT ]
  • Full B cell reconstitution [ Time Frame: 12 months post HCT ]
  • Full B cell reconstitution [ Time Frame: 24 months post HCT ]
  • Engraftment [ Time Frame: 100 days ]
  • Engraftment [ Time Frame: 6 months ]
  • Engraftment [ Time Frame: 12 months ]
  • Engraftment [ Time Frame: 24 months ]
  • Infections [ Time Frame: 24 months ]
  • Growth and Nutrition [ Time Frame: 24 months ]
  • Graft versus Host Disease [ Time Frame: 24 months ]
  • Occurrence of autoimmunity requiring treatment
  • Neurodevelopment/Neurocognition [ Time Frame: 24 months ]
  • Other complications of HCT needing treatment
  • Quality of Life [ Time Frame: 24 months ]
Not Provided
Not Provided
 
Natural History Study of SCID Disorders
A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children With SCID Disorders (RDCRN PIDTC-6901)
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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:
Peripheral blood samples, tissue, and bone marrow samples collected during participation in this study.
Non-Probability Sample
Patients with diagnosis of SCID or SCID variants treated at Consortium Centers from 1968-2010
  • SCID
  • Leaky SCID
  • Omenn Syndrome
  • Reticular Dysgenesis
  • ADA Deficiency
  • XSCID
Not Provided
  • Classic SCID (Stratum A)
    Patients with classic SCID after allogeneic hematopoietic stem cell transplantation
  • Leaky SCID, Omenn syndrome, or RS (Stratum B)
    Patients with leaky SCID, Omenn syndrome, or Reticular Dysgenesis (RS) after allogeneic hematopoietic stem cell transplantation
  • ADA Deficiency or XSCID treated with PEG-ADA (Stratum C)
    Patients with ADA Deficiency or XSCID who are treated with PEG-ADA (patients with ADA Deficiency) or patients who are treated with gene therapy (ADA Deficiency or XSCID)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
209
August 2019
August 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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.

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 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.
Sexes Eligible for Study: All
Child, Adult, Senior
No
Canada,   United States
 
 
NCT01186913
DAIT RDCRN PIDTC-6901
No
Not Provided
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Office of Rare Diseases (ORD)
Principal Investigator: Chris Dvorak, MD UCSF Children's Hospital
Principal Investigator: Morton J. Cowan, MD UCSF Children's Hospital
National Institute of Allergy and Infectious Diseases (NIAID)
October 2017