Recruitment and Apheresis Collection of Peripheral Blood Hematopoietic Stem Cells, Mononuclear Cells and Granulocytes
- Conditions
- GranulomaGenetic Disease, X-LinkedGenetic Disease, InbornGranulomatous Disease, ChronicLeukocyte Disease
- Registration Number
- NCT00001405
- Brief Summary
The research 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 that will be used in the laboratory and/or in the clinic to develop new cell therapies for patients with inherited or acquired disorders of immunity or blood cells. Development of novel cellular therapies requires access to HSC, Mononuclear Cells and/or granulocytes as the essential starting materials for the pre-clinical laboratory development of gene therapies and other engineered cell products. HSC or blood cells from healthy adult volunteers serve both as necessary experimental controls and also as surrogates for patient cells for clinical scale-up development. HSC or blood cells from patients serve both as the necessary experimental substrate for novel gene therapy and cellular engineering development for specific disorders and as pre-clinical scale up of cellular therapies. Collection of cells from adult patients collected in the NIH Department of Transfusion Medicine (DTM) under conditions conforming to accepted blood banking clinical practice may also be used directly in or cryopreserved for future use in other NIH protocols that have all required regulatory approvals allowing such use. In summary, the research goal of this protocol is the collection of HSC or blood cells that may be used for both laboratory research and/or for clinical treatment in other approved protocols.
- Detailed Description
The research 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 that will be used in the laboratory and/or in the clinic to develop new cell therapies for patients with inherited or acquired disorders of immunity or blood cells. Development of novel cellular therapies requires access to HSC, Mononuclear Cells and/or granulocytes as the essential starting materials for the pre-clinical laboratory development of gene therapies and other engineered cell products. HSC or blood cells from healthy adult volunteers serve both as necessary experimental controls and also as surrogates for patient cells for clinical scale-up development. HSC or blood cells from patients serve both as the necessary experimental substrate for novel gene therapy and cellular engineering development for specific disorders and as pre-clinical scale up of cellular therapies. Collection of cells from adult patients collected in the NIH Department of Transfusion Medicine (DTM) under conditions conforming to accepted blood banking clinical practice may also be used directly in or cryopreserved for future use in other NIH protocols that have all required regulatory approvals allowing such use. In summary, the research goal of this protocol is -the collection of HSC or blood cells that may be used for both laboratory research and/or for clinical treatment in other approved protocols.
Participants include: 1. Adult patients with any primary immune deficiency (PID) or other blood disorder where collection is both for clinical use in another approved treatment protocol to benefit the patient and for laboratory research; 2. Adult patients with any primary immune deficiency (PID) or blood disorder where collection is for laboratory research use only. 3. Healthy adult volunteers where the collection is for laboratory research use only.
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 of care method used to mobilize HSC to the peripheral blood prior to apheresis, and will be used for most subjects. Plerixafor (Mozobil) is approved as standard of care for use in combination with G-CSF to mobilize HSC.
Some adult patients will have a clinical scale aspiration collection of bone marrow to obtain HSC for clinical use in another approved treatment protocol. Some adult participants may have a small sample needle aspiration collection of bone marrow obtained for laboratory research purposes only.
Mononuclear cells and/or Granulocytes (gran) will be collected from peripheral blood by apheresis following no stimulation, using G-CSF alone, or a using a combined single dose of G-CSF (480mcg) and Dexamethasone (8mg) prior to collection as is the standard of care pre-treatment used in the NIH DTM for collection of granulocyte transfusions from healthy donors.
As noted, HSC, mononuclear cells, and gran collection from patients with PID or other blood disorders may be used for laboratory research or may be designated for future clinical treatment of the patient under separate treatment protocol. HSC, mononuclear cells, and gran collection from healthy volunteers will be designated entirely for laboratory research.
HSC will be used for the following 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 related or unrelated donor transplantation.
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 850
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Mobilize to peripheral blood mononuclear cells and granulocytes 1/1/2025 3.To efficiently and safely collect peripheral blood mononuclear cells and granulocytes from adult subjects with chronic granulomatous disease or other PID affecting granulocyte function, or from adult healthy donors volunteers for preclinical cell therapy studies, following either no stimulation, G-CSF or dexamethasone alone, or combined single dose G-CSF and dexamethasone as per DTM protocol depending on the number of cells desired.
Mobilize to peripheral blood and apheresis collect CD34+PBSC of PID patients for clinical treatment and in part (or entirely) for laboratory research 1/1/2025 1. To efficiently and safely mobilize to the peripheral blood and apheresis collect CD34+ PBSC patients with any inherited primary immune deficiency (PID) or other blood disorders where PBSC from these patients may be designated entirely or in part for future clinical treatment of the patient
Mobilize to the peripheral blood and apheresis collect CD34+PBSC from healthy volunteers for research 1/1/2025 2. To efficiently and safely mobilize to the peripheral blood and apheresis collect CD34+ PBSC from healthy volunteers, which will be designated entirely for laboratory research.
laboratory studies of PBSC and bone marrow HSC 1/1/2025 6.To conduct laboratory studies of PBSC and bone marrow HSC obtained from patients with PID or healthy volunteers in order to: study the functional properties of immune cells arising from hematopoietic stem cells in ex vivo culture systems and in NOD/SCID or NOG mice capable of supporting a human hematopoietic stem cellchimeric marrow xenograft.
laboratory studies of mononuclear cells and granulocytes obtained from patients with PID or healthy volunteers 1/1/2025 7.To conduct laboratory studies of mononuclear cells and granulocytes obtained from patients with PID or healthy volunteers in order to: Develop effective methods to restore immunologic function to defective granulocytes/mononuclear cells utilizing mRNA electroporation. Develop methodology of using autologous corrected granulocytes/mononuclear cells for the treatment of infections in immunedeficient patients.
bone marrow harvest 1/1/2025 4.To perform a bone marrow harvest by needle aspiration using standard of medical care methods from adult patients with PID or other blood disorder in sufficient quantity cryopreserved in CC DTM to serve as the source of autologous HSC for gene transfer ex vivo transduction if that patient is enrolled in a separate IRB approved protocol of gene transfer treatment designed to treat the genetically defined type of PID affecting that patient; and the patient has been unable to mobilize and have collected sufficient PBSC to qualify for treatment in that protocol.
bone marrow by needle aspiration 1/1/2025 5.To obtain from adult patients with PID or other blood disorder and from adult healthy volunteers a small sample of bone marrow by needle aspiration from bone marrow aspirates, where the purpose for this aspirate is to obtain bone marrow HSC for laboratory research comparing these cells to the biological properties of PBSC.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States