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Apheresis of Patients With Immunodeficiency

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ClinicalTrials.gov Identifier: NCT01212055
Recruitment Status : Recruiting
First Posted : September 30, 2010
Last Update Posted : October 1, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

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 Center.
  • On day 5, participants will have a single leukapheresis procedure to collect the stem cells from the blood.
  • No additional treatment will be provided as part of this protocol. The cells that are collected will be used fore experiments in the lab and will not be used to treat individuals with these diseases.

Condition or disease
LAD-1 DOCK8 GATA2 Deficancy

Detailed Description:

Background

Primary immunodeficiency diseases (PID) represent candidate genetic disorders for new therapeutic approaches. Our laboratory is developing new therapies for patients with PID using autologous CD34+ hematopoietic stem cells (HSC). Newer therapies 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 all three diseases the gene has been cloned. Testing new therapies for these diseases 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 (Filgrastim) mobilized peripheral blood CD34+ hematopoietic stem cells (HSC) for laboratory research studies for DOCK8 deficiency, LAD-1, and GATA2 Deficiency.

Eligibility

Patients 18-40 years old with DOCK8 deficiency, LAD-1, and GATA2 Deficiency who meet the eligibility requirements will be considered for this protocol.

Design

Patients 18-40 years old with DOCK8 deficiency, LAD-1, and GATA2 Deficiency will receive five days of G- Filgrastim followed by a single apheresis. CD34+ cells will be selected and frozen in aliquots by the Cell Processing Section of the Department of Transfusion Medicine. No treatments, or investigational therapy will be administered on this protocol.

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Study Type : Observational
Estimated Enrollment : 6 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Apheresis and CD34+ Selection of Mobilized Peripheral Blood CD34+ Cells From Patients With DOCK8 Deficiency, LAD-1, and GATA2 Deficiency
Actual Study Start Date : November 8, 2010


Group/Cohort
Cohort 1
Patients with DOCK8 deficiency, LAD-1, or GATA2 Deficiency



Primary Outcome Measures :
  1. 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 ]
    Obtain granulocyte colony stimulating factor mobilized peripheral blood CD34+ hematopoietic stem cells (HSC) by apheresis for laboratory research studies for DOCK8 deficiency, LAD-1, and GATA2 deficiency.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with DOCK8 deficiency, LAD-1, and GATA2 Deficiency who are between 18 and 40 years of age meeting the eligibility criteria will be considered for the protocol.
Criteria

-INCLUSION CRITERIA - PATIENT

  1. Patient age of 18-40 years.
  2. Diagnosis of DOCK8 deficiency, LAD-1, or GATA2 Deficiency:

    -DOCK8 deficiency

    • Homozygous or compound heterozygous mutations in the DOCK8 gene.

      -LAD-1

    • Less than 10% CD18 expression on the neutrophil surface.

      -GATA2 Deficiency

    • Deleterious mutation of GATA2 Gene
  3. Serum creatinine <1.5 mg/dL.
  4. Total Bilirubin < 3mg/dl, ALT and AST < 5X upper limit of normal.
  5. Ability to give informed consent.
  6. Adequate venous access for peripheral apheresis, or consent to use a temporary central venous catheter for apheresis.
  7. Female patients of childbearing age must have a negative urine pregnancy test within one week of beginning Filgrastim administration.

EXCLUSION CRITERIA - PATIENT

  1. HIV infection.
  2. Chronic hepatitis B or hepatitis C virus infection.
  3. History of psychiatric disorder which may compromise compliance with protocol, or which does not allow for appropriate informed consent.
  4. Active infection that is not responding to antimicrobial therapy.
  5. Pregnant women may not participate per OHSRP SOP 14B, Research Involving Pregnant Women, Human Fetuses and Neonates.
  6. Any female who is breastfeeding as the effects of filgrastim on infants is not known.
  7. Sexually active individuals capable of becoming pregnant who are unable or unwilling to use effective form(s) of contraception during the 10 days surrounding filgrastim administration and apheresis procedure(s). Effective forms of contraception include one or more of the following: intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligation/hysterectomy, partner's vasectomy, barrier methods, (condom, diaphragm, or cervical cap), or abstinence. Males on the protocol must use an effective form of contraception at study entry.
  8. Presence of active malignancy in another organ system other than the hematopoietic system.
  9. Patients with active pulmonary disease.
  10. History of hypertension that is not controlled by medication, stroke, or severe heart disease. Individuals with symptomatic angina will be considered to have severe heart disease and will not be eligible.
  11. Other medical contraindications to stem cell donation (i.e. severe atherosclerosis, autoimmune disease, iritis or episcleritis, deep venous thrombosis, cerebrovascular accident).
  12. Thrombocytopenia (platelets less than 50,000 per microlitre) at baseline evaluation.
  13. Patients receiving experimental therapy or investigational agents.
  14. Sensitivity to filgrastim or to E. coli-derived recombinant protein products.
  15. Patients must test negative for transfusion-transmissible infectious agents, including hepatitis B (HBsAg), hepatitis C (anti-HCV), HIV (anti-HIV-1/2).

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): NCT01212055


Contacts
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Contact: Dennis D Hickstein, M.D. (240) 760-6169 hicksted@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Dennis D Hickstein, M.D. National Cancer Institute (NCI)
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01212055    
Other Study ID Numbers: 100201
10-C-0201
First Posted: September 30, 2010    Key Record Dates
Last Update Posted: October 1, 2020
Last Verified: September 24, 2020
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
PBSC Collection
Immunodeficiency
Spectra Apheresis System
Stem Cell Mobilization
Leukapheresis