Use of G-CSF to Obtain Blood Cell Precursors
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|ClinicalTrials.gov Identifier: NCT00001405|
Recruitment Status : Recruiting
First Posted : November 4, 1999
Last Update Posted : August 9, 2018
|First Submitted Date||November 3, 1999|
|First Posted Date||November 4, 1999|
|Last Update Posted Date||August 9, 2018|
|Study Start Date||February 9, 1994|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures
|Original Primary Outcome Measures||Not Provided|
|Change History||Complete list of historical versions of study NCT00001405 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||Use of G-CSF to Obtain Blood Cell Precursors|
|Official Title||Recruitment and Apheresis Collection of Peripheral Blood Hematopoietic Stem Cells,Mononuclear Cells and Granulocytes|
This protocol is designed to study the techniques needed to develop gene therapy or other treatments for certain inherited immune system diseases.
Healthy normal volunteers between 18 and 65 years of age and patients with chronic granulomatous disease (CGD), X-linked severe combined immune deficiency (X-SCID), leukocyte adhesion deficiency (LAD), interferon gamma receptor deficiency (IGR-deficiency) or other inherited diseases affecting precursor blood cells-bone marrow cells that generate blood cells-may be eligible for this study. Patients who have had repeated severe infections possibly due to an inherited blood cell abnormality may also participate. Candidates will be screened with a medical history, physical examination and blood tests.
Patients with an active infection will be hospitalized during this study. Uninfected participants will be seen as outpatients at the NIH Clinical Center. Participants will have the following procedures:
Four months or more after the end of the study, participants will be asked to repeat the entire procedure to examine the effects of two cycles of G-CSF mobilization in the same individual. This second cycle is optional.
The goal of this study is to obtain CD34+ hematopoietic stem cells (HSC) from peripheral blood and/or bone marrow, and Mononuclear Cells (lymphocytes and monocytes), and granulocytes (grans) from peripheral blood. These collections maybe used for clinical treatment or laboratory research.
Participants include: 1. Patients with any primary immune deficiency (PID) where collection is for clinical use to benefit the patient; 2. Patients with any primary immune deficiency (PID) where collection is for laboratory research use only. 3. Healthy sibling or other related donor of those patients with PID in need of an allogeneic stem cell transplant direct donation for a designated patient; 4. Healthy adult volunteers.
The majority of subjects will have HSC collected from peripheral blood by apheresis. Daily subcutaneous injections of G-CSF (granulocyte colony stimulating factor/filgrastim) for 5 to 6 days is a standard method used to mobilize HSC to the peripheral blood prior to apheresis, and will be used for most subjects. Plerixafor (Mozobil) is approved for use in combination with GCSF to mobilize HSC and will be used in patients, or sibling/related donors undergoing collection of HSC by apheresis.
Some patients and healthy sibling/related donors will have a clinical scale aspiration collection of bone marrow to obtain HSC for clinical use. Some participants may have a small sample needle aspiration collection of bone marrow obtained for research purposes.
Mononuclear cells and/or Granulocytes (gran) will be collected from peripheral blood by apheresis following no stimulation, G-CSF alone, or a combined single dose of G-CSF (480mcg) and Dexamethasone (8mg) prior to collection as is used in the Department of Transfusion Medicine.
HSC, mononuclear cells, and gran collection from patients with PID may be used for laboratory research or may be designated for future clinical treatment of the patient under separate treatment protocol. HSC collections from healthy sibling/related donor of those patients with PID in need of an allogeneic stem cell transplant will be designated for clinical treatment of the related patient. HSC, mononuclear cells, and gran collection from healthy volunteers will be designated entirely for laboratory research.
HSC will be used for the following three clinical purposes, where clinical treatments would occur under separate IRB approved protocols: 1. Autologous HSC from patients may be genetically modified and infused into the patient for treatment of an infection or the underlying disease (Gene therapy); 2. Autologous HSC from patients may serve as back up (rescue product) for patients undergoing matched unrelated donor transplantation or haploidential transplantation; 3. HSC from a sibling/related donor may be used as a directed donation for allogeneic transplant of the related patient. Mononuclear Cells (lymphocytes and monocytes) and granulocytes will be used for the following clinical purposes, 1. Autologous lymphocytes may be genetically modified and infused into the patient for treatment of an infection or the underlying disease (Gene therapy); 2. Autologous lymphocytes, monocytes and granulocytes (neutrophils) may be transfected with mRNAs to transiently express a therapeutic protein for treatment of an infection or the underlying disease (Gene therapy).
HSC, lymphocytes, monocytes and granulocytes will be used for laboratory research studies that include: Delineating the pathophysiology of inherited immune deficiencies; Delineating the physiology of and improving engraftment of hematopoietic stem cells; Determining how hematopoietic stem cells may be maintained in ex vivo culture without losing pluripotent potential; Delineating the molecular mechanisms responsible for lineage specific differentiation; Developing efficient methods for gene transfer into hematopoietic stem cells for corrective gene therapy; Developing methods for restoration of function in defective peripheral blood monocytes and/or granulocytes; Further characterization of peripheral blood monocytes and/or granulocytes from patients with PID.
|Study Design||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition||Chronic Granulomatous Disease|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Study Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
Patients (Patients with a genetically defined PID or clinical history consistent with PID)
Healthy Donors (HLA matched sibling or other related donor of a patient with PID in need of an allogeneic hematopoietic stem cell transplant)
For PBMCs and grans collections, adult subjects with known genetic mutations may participate as healthy volunteers for research purposes as long as the other criteria listed above are fulfilled.
Healthy Volunteers and Healthy Donors
Patients or Healthy Donors being considered for clinical scale bone marrow harvesting
|Ages||2 Years to 70 Years (Child, Adult, Older Adult)|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries||United States|
|Removed Location Countries|
|Other Study ID Numbers||940073
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )|
|Study Sponsor||National Institute of Allergy and Infectious Diseases (NIAID)|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||December 18, 2017|