Clinical Trial: Apheresis of Patients With Immunodeficiency

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Apheresis and CD34+ Selection of Mobilized Peripheral Blood CD34+ Cells From Patients With DOCK8 Deficiency, LAD-1, and GATA2 Deficiency

Brief Summary:

Background:

- Gene therapy is being investigated as a possible treatment for individuals with immunodeficiency diseases or other conditions that make it difficult to fight off infection. Gene therapy avoids problems with donor identification and possible rejection of bone marrow transplant by using the patient s own modified blood cells to help treat the disease. Researchers are interested in collecting stem cells from the blood of individuals with immunodeficiency diseases in order to use the cells to develop potential gene therapy treatments.

Objectives:

- To collect blood stem cells from patients with immunodeficiency diseases tto test our ability to correct the defects of these cells in the test tube. .

Eligibility:

• Individuals between 18 and 40 years of age with immunodeficiency diseases.
• Individuals with human immunodeficiency virus (HIV) will not be able to participate in this study.

Design:

• Participants will provide an initial blood sample for disease screening (such as hepatitis B and C, syphilis, or viruses like the Epstein-Barr virus, herpes simplex virus, or toxoplasmosis) and to check kidney and liver function.
• Starting 5 days before blood donation, participants will receive daily injections of a drug called G-CSF (granulocyte colony stimulating factor, or filgrastim), which pushes stem cells out of the bone marrow and into the bloodstream. Participants will receive the injections at the National Institutes of Health Clinical
  

  Detailed Summary:

  BACKGROUND:

  Primary immunodeficiency diseases (PID) represent candidate genetic disorders for new therapeutic approaches. Our laboratory is developing gene therapy for patients with PID using autologous CD34+ hematopoietic stem cells (HSC). Gene therapy may circumvent problems with allogeneic HSC transplantation, especially graft rejection and graft-versus-host-disease. We are particularly interested in three PID: Dedicator of CytoKinesis-8 (DOCK8) deficiency, Leukocyte Adhesion Deficiency type 1 (LAD-1), and GATA2 Deficiency. For DOCK8 deficiency, and LAD-1, the disease gene has been cloned. The genetic basis for MonoMAC has now been determined to be due to mutations in GATA2.. Testing new vector constructs and transduction conditions for gene therapy would be considerably enhanced by the acquisition of peripheral blood CD34+ cells from patients with these immunodeficiency diseases.

  OBJECTIVES:

  To provide a source of granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood CD34+ hematopoietic stem cells (HSC) for laboratory research studies including optimization of vector and transduction conditions for gene therapy for DOCK8 deficiency, LAD-1, and MonoMAC.

  ELIGIBILITY:

  Patients 15-40 years old with DOCK8 deficiency, LAD-1, and MonoMAC who meet the eligibility requirements will be considered for this protocol.

  DESIGN:

  Patients 15-40 years old with DOCK8 deficiency, LAD-1, and MonoMAC will receive five days of G-CSF followed by a single apheresis. CD34+ cell will be selected and frozen in aliquots by the Cell Processing Section of the Department of Transfusion
  Sponsor: National Cancer Institute (NCI)
  

  Current Primary Outcome: To collect blood stem cells from patients with immunodeficiency diseases to test our ability to correct the defects of these cells in the test tube. [ Time Frame: 5 days ]
  
  

  Original Primary Outcome:
  
  

  Current Secondary Outcome:
  
  

  Original Secondary Outcome:
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: September 29, 2010
  Date Started: August 31, 2010
  Date Completion:
  Last Updated: April 26, 2017
  Last Verified: April 18, 2017