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
  Purpose

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.


Condition
SCID
Leaky SCID
Omenn Syndrome
Reticular Dysgenesis
ADA Deficiency
XSCID

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children With SCID Disorders (RDCRN PIDTC-6901)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Overall survival following HCT [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 265
Study Start Date: August 2010
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
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)

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01186913

  Show 33 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Rebecca Buckley, MD Duke University School of Medicine
Principal Investigator: Morton J. Cowan, MD UCSF Children's Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01186913     History of Changes
Obsolete Identifiers: NCT02108067
Other Study ID Numbers: DAIT RDCRN PIDTC-6901
Study First Received: August 20, 2010
Last Updated: June 11, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Congenital Abnormalities
Severe Combined Immunodeficiency
Agammaglobulinemia
Leukopenia
X-Linked Combined Immunodeficiency Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Blood Protein Disorders
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Leukocyte Disorders
Genetic Diseases, X-Linked
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on July 28, 2014