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Natural History Study of SCID Disorders

This study is currently recruiting participants.
Verified September 2016 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01186913
First Posted: August 23, 2010
Last Update Posted: September 28, 2016
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)
  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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 265
Study Start Date: August 2010
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (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

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with diagnosis of SCID or SCID variants treated at Consortium Centers from 1968-2010
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01186913


  Show 42 Study Locations
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Office of Rare Diseases (ORD)
Investigators
Principal Investigator: Rebecca Buckley, MD Duke University
Principal Investigator: Morton J. Cowan, MD UCSF Children's Hospital
  More Information

Additional Information:
Publications:
Dvorak CC, Cowan MJ, Logan BR, Notarangelo LD, Griffith LM, Puck JM, Kohn DB, Shearer WT, O'Reilly RJ, Fleisher TA, Pai SY, Hanson IC, Pulsipher MA, Fuleihan R, Filipovich A, Goldman F, Kapoor N, Small T, Smith A, Chan KW, Cuvelier G, Heimall J, Knutsen A, Loechelt B, Moore T, Buckley RH. The natural history of children with severe combined immunodeficiency: baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901. J Clin Immunol. 2013 Oct;33(7):1156-64. doi: 10.1007/s10875-013-9917-y. Epub 2013 Jul 2.
Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. J Allergy Clin Immunol. 2014 Apr;133(4):1092-8. doi: 10.1016/j.jaci.2013.09.044. Epub 2013 Nov 28.
Haddad E, Allakhverdi Z, Griffith LM, Cowan MJ, Notarangelo LD. Survey on retransplantation criteria for patients with severe combined immunodeficiency. J Allergy Clin Immunol. 2014 Feb;133(2):597-9. doi: 10.1016/j.jaci.2013.10.022. Epub 2013 Dec 10.
Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Pai SY, Ballard B, Bauer SC, Bleesing JJ, Boyle M, Brower A, Buckley RH, van der Burg M, Burroughs LM, Candotti F, Cant AJ, Chatila T, Cunningham-Rundles C, Dinauer MC, Dvorak CC, Filipovich AH, Fleisher TA, Bobby Gaspar H, Gungor T, Haddad E, Hovermale E, Huang F, Hurley A, Hurley M, Iyengar S, Kang EM, Logan BR, Long-Boyle JR, Malech HL, McGhee SA, Modell F, Modell V, Ochs HD, O'Reilly RJ, Parkman R, Rawlings DJ, Routes JM, Shearer WT, Small TN, Smith H, Sullivan KE, Szabolcs P, Thrasher A, Torgerson TR, Veys P, Weinberg K, Zuniga-Pflucker JC; workshop participants. Primary Immune Deficiency Treatment Consortium (PIDTC) report. J Allergy Clin Immunol. 2014 Feb;133(2):335-47. doi: 10.1016/j.jaci.2013.07.052. Epub 2013 Oct 15.
Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Shearer WT, Burroughs LM, Torgerson TR, Decaluwe H, Haddad E; workshop participants. Primary Immune Deficiency Treatment Consortium (PIDTC) update. J Allergy Clin Immunol. 2016 Aug;138(2):375-85. doi: 10.1016/j.jaci.2016.01.051. Epub 2016 Apr 22. Review.
Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, Kapoor N, Hanson IC, Filipovich AH, Jyonouchi S, Sullivan KE, Small TN, Burroughs L, Skoda-Smith S, Haight AE, Grizzle A, Pulsipher MA, Chan KW, Fuleihan RL, Haddad E, Loechelt B, Aquino VM, Gillio A, Davis J, Knutsen A, Smith AR, Moore TB, Schroeder ML, Goldman FD, Connelly JA, Porteus MH, Xiang Q, Shearer WT, Fleisher TA, Kohn DB, Puck JM, Notarangelo LD, Cowan MJ, O'Reilly RJ. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014 Jul 31;371(5):434-46. doi: 10.1056/NEJMoa1401177.
Griffith LM, Cowan MJ, Notarangelo LD, Puck JM, Buckley RH, Candotti F, Conley ME, Fleisher TA, Gaspar HB, Kohn DB, Ochs HD, O'Reilly RJ, Rizzo JD, Roifman CM, Small TN, Shearer WT; Workshop Participants. Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management. J Allergy Clin Immunol. 2009 Dec;124(6):1152-60.e12. doi: 10.1016/j.jaci.2009.10.022.
Griffith LM, Cowan MJ, Kohn DB, Notarangelo LD, Puck JM, Schultz KR, Buckley RH, Eapen M, Kamani NR, O'Reilly RJ, Parkman R, Roifman CM, Sullivan KE, Filipovich AH, Fleisher TA, Shearer WT. Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: current status and critical needs. J Allergy Clin Immunol. 2008 Dec;122(6):1087-96. doi: 10.1016/j.jaci.2008.09.045. Epub 2008 Nov 6.

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
First Submitted: August 20, 2010
First Posted: August 23, 2010
Last Update Posted: September 28, 2016
Last Verified: September 2016

Additional relevant MeSH terms:
Severe Combined Immunodeficiency
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases


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