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

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Fredrick Goldman, MD    205-939-5855    fgoldman@peds.uab.edu   
Principal Investigator: Fredrick Goldman, MD         
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Renna Killen, RN    323-361-2217    rkillen@chla.usc.edu   
Principal Investigator: Neena Kapoor, MD         
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095-1752
Contact: Theodore Moore, MD    310-825-6708    TBMoore@mednet.ucla.edu   
Principal Investigator: Theodore Moore, MD         
University of California San Francisco Children's Hospital Recruiting
San Francisco, California, United States, 94143-1278
Contact: Elizabeth Dunn, MA    415-502-0203    DunnE@peds.ucsf.edu   
Principal Investigator: Morton Cowan, MD         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Matthew Porteus, MD    650-725-6520    mporteus@stanford.edu   
Principal Investigator: Matthew Porteus, MD         
United States, Colorado
Children's Hospital Denver Recruiting
Denver, Colorado, United States, 80220
Contact: John Craddock, MD    720-777-3328    John.Craddock@childrenscolorado.org   
Principal Investigator: John Craddock, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010-2970
Contact: Brett Loechelt, MD    202-476-2805    BLoechel@childrensnational.org   
Principal Investigator: Brett Loechelt, MD         
United States, Florida
All Children's Hospital, St. Petersburg FL Recruiting
St. Petersburg, Florida, United States, 33701
Contact: Aleksandra Petrovic, MD    727-767-6856    Aleksandra.Petrovic@allkids.org   
Principal Investigator: Aleksandra Petrovic, MD         
United States, Georgia
Children's Healthcare of Atlanta/Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact: Elizabeth Stenger, MD    404-785-1272    Elizabeth.Stenger@choa.org   
Principal Investigator: Elizabeth Stenger, MD         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60614
Contact: Morris Kletzel, MD    773-880-4598    MKletzel16@northwestern.edu   
Principal Investigator: Morris Kletzel, MD         
United States, Louisiana
Children's Hospital/Louisiana State University Health Sciences Center Recruiting
New Orleans, Louisiana, United States, 70118
Contact: Lolie Yu, MD    504-896-9740    lyu@lsuhsc.edu   
Principal Investigator: Lolie Yu, MD         
United States, Maryland
NIH Clinical Center Genetic Immunotherapy Section Not yet recruiting
Bethesda, Maryland, United States, 20892
Contact: Elizabeth Kang, MD    301-402-7567    ekang@niaid.nih.gov   
Principal Investigator: Elizabeth Kang, MD         
United States, Massachusetts
Children's Hospital Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Sung-Yun Pai, MD    617-919-2508    sung-yun.pai@childrens.harvard.edu   
Principal Investigator: Sung-Yun Pai, MD         
United States, Michigan
University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: James Connelly, MD    737-936-4000    jaconnel@med.umich.edu   
Principal Investigator: James Connelly, MD         
United States, Minnesota
University of Minnesota Medical Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Angie Smith, MD    612-626-2778    smith719@umn.edu   
Principal Investigator: Angie Smith, MD         
United States, Missouri
Cardinal Glennon Children's Medical Center Recruiting
St. Louis, Missouri, United States, 63104
Contact: Wendy Sanders, RN    314-268-2700 ext 3513    Wendy_Sanders@ssmhc.com   
Principal Investigator: Alan Knutsen, MD         
Washington University St Louis Children's Hospital Recruiting
St. Louis, Missouri, United States, 63110
Contact: Shalini Shenoy, MD    314-454-6018    shenoy@wustl.edu   
Principal Investigator: Shalini Shenoy, MD         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Alfred Gillio, MD    201-996-5645    AGillio@HackensackUMC.org   
Principal Investigator: Alfred Gillio, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Richard J O'Reilly    212-639-5957    oreillyr@mskc.org   
Principal Investigator: Richard J O'Reilly, MD         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Rebecca Buckley, MD    919-684-2922    buckl003@mc.duke.edu   
Principal Investigator: Rebecca Buckley, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Lisa Filipovich, MD    513-636-5917    lisa.Filipovich@cchmc.org   
Principal Investigator: Lisa Filipovich, MD         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Evan Shereck, MD    503-494-0829    Shereck@ohsu.edu   
Principal Investigator: Evan Shereck, MD         
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kathleen Sullivan, MD, PhD    215-590-1697    sullivak@mail.med.upenn.edu   
Principal Investigator: Kathleen Sullivan, MD, PhD         
United States, Texas
University of Texas Southwestern Medical Center/Children's of Dallas Recruiting
Dallas, Texas, United States, 75390-9263
Contact: Victor Aquino, MD    214-648-8800    victor.aquino@utsouthwestern.edu   
Principal Investigator: Victor Aquino, MD         
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030-2399
Contact: Chivon McMullen-Jackson, RN, BSN    832-824-1339    cdmcmull@texaschildrens.org   
Principal Investigator: William Shearer, MD         
Methodist Children's Hospital of South Texas/Texas Transplant Institute Recruiting
San Antonio, Texas, United States, 78229
Contact: Troy Quigg, MD    210-575-7348    Troy.Quigg@MHShealth.com   
Principal Investigator: Troy Quigg, MD         
United States, Utah
Primary Children's Medical Center/University of Utah Recruiting
Salt Lake City, Utah, United States, 84113
Contact: Michael Pulsipher, MD    801-662-4830    michael.pulsipher@hsc.utah.edu   
Principal Investigator: Michael Pulsipher, MD         
United States, Washington
Seattle Children's Research Institute Recruiting
Seattle, Washington, United States, 98101
Contact: Lauri M Burroughs, MD    206-667-2396    lburroug@fhcrc.org   
Principal Investigator: Lauri M Burroughs, MD         
United States, Wisconsin
University of Wisconsin/ American Family Children's Hospital Recruiting
Madison, Wisconsin, United States, 53705-2275
Contact: Kenneth DeSantes, MD    608-263-8563    kbdesantes@pediatrics.wisc.edu   
Principal Investigator: Kenneth DeSantes         
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226-4874
Contact: Monica S Thakar, MD    414-266-6848    mthakar@mcw.edu   
Principal Investigator: Monica S Thakar, MD         
Canada, British Columbia
British Columbia Children's Hospital Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Jeffrey Davis, MD    604-875-3577    jdavis@cw.bc.ca   
Principal Investigator: Jeffrey Davis, MD         
Canada, Manitoba
Cancer Care Manitoba Recruiting
Winnipeg, Manitoba, Canada, R3E 0V9
Contact: Geoff Cuvelier, MD    204-787-8689    geoff.cuvelier@cancercare.mb.ca   
Principal Investigator: Geoff Cuvelier, MD         
Canada, Quebec
CHU St. Justine Recruiting
Montreal, Quebec, Canada, H3T 1C5
Contact: Elie Haddad, MD    514-345-4931 ext 6217    elie.haddad@umontreal.ca   
Principal Investigator: Elie Haddad, MD         
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:
Severe Combined Immunodeficiency
Leukopenia
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Leukocyte Disorders
Hematologic Diseases

ClinicalTrials.gov processed this record on September 18, 2014