Natural History Study of SCID Disorders

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01186913
First received: August 20, 2010
Last updated: June 11, 2014
Last verified: June 2014

August 20, 2010
June 11, 2014
August 2010
August 2015   (final data collection date for primary outcome measure)
Overall survival following HCT [ Time Frame: 4 years ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
  • Full T cell reconstitution [ Time Frame: 12 months post HCT ] [ Designated as safety issue: No ]
  • Full T cell reconstitution [ Time Frame: 24 months post HCT ] [ Designated as safety issue: No ]
  • Full B cell reconstitution [ Time Frame: 12 months post HCT ] [ Designated as safety issue: No ]
  • Full B cell reconstitution [ Time Frame: 24 months post HCT ] [ Designated as safety issue: No ]
  • Engraftment [ Time Frame: 100 days ] [ Designated as safety issue: No ]
  • Engraftment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Engraftment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Engraftment [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Infections [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Growth and Nutrition [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Graft versus Host Disease [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Occurrence of autoimmunity requiring treatment [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
  • Neurodevelopment/Neurocognition [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Other complications of HCT needing treatment [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Full T cell reconstitution [ Time Frame: 6 months post HCT ] [ Designated as safety issue: No ]
  • Full T cell reconstitution [ Time Frame: 12 months post HCT ] [ Designated as safety issue: No ]
  • Full T cell reconstitution [ Time Frame: 24 months post HCT ] [ Designated as safety issue: No ]
  • Full B cell reconstitution [ Time Frame: 12 months post HCT ] [ Designated as safety issue: No ]
  • Full B cell reconstitution [ Time Frame: 24 months post HCT ] [ Designated as safety issue: No ]
  • Engraftment [ Time Frame: 100 days ] [ Designated as safety issue: No ]
  • Engraftment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Engraftment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Engraftment [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Infections [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Growth and Nutrition [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Graft versus Host Disease [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Occurence of autoimmunity requiring treatment [ Designated as safety issue: No ]
  • Neurodevelopment/Neurocognition [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Other complications of HCT needing treatment [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: 24 months ] [ Designated as safety issue: No ]
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)

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.

Not Provided
Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Not Provided
Non-Probability Sample

Patients will be selected from 14 participating centers and additional Pediatric Blood and Marrow Transplant Consortium centers caring for SCID patients in North America

  • 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)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
265
August 2015
August 2015   (final data collection date for primary outcome measure)

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
Both
Not Provided
No
United States,   Canada
 
NCT01186913
DAIT RDCRN PIDTC-6901
No
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Office of Rare Diseases (ORD)
Principal Investigator: Rebecca Buckley, MD Duke University School of Medicine
Principal Investigator: Morton J. Cowan, MD UCSF Children's Hospital
National Institute of Allergy and Infectious Diseases (NIAID)
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP