Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives

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Descriptive Information
Brief Title † Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Official Title † Use of Granulocyte Colony Stimulating Factor (G-CSF) Mobilized Leukapheresis Collections From Healthy Volunteers to Develop Improved Methods of Stem Cell and Lymphocyte Selection for Allogeneic Transplantation
Brief Summary Bone marrow transplants (BMT) are one form of treatment for disorders of the blood, including leukemia. However, because the procedure is often associated with potentially life-threatening reactions, it is usually reserved for patients with serious illnesses under the age of 60 years old. One serious reaction complicating bone marrow transplants is referred to as graft-versus-host disease (GVHD). GVHD is a potentially fatal incompatibility reaction. The reaction is caused by antigens found on the cells of the patient that are not present on the cells of the donor. The antigens are recognized by transplanted white blood cells (lymphocytes). These lymphocytes begin attacking the recipient s cells and tissues and may lead to death. In order to avoid GVHD, researchers have developed a technique using peripheral blood instead of bone marrow that allows transplantation of stem cells and removal of lymphocytes. Stem cells are the cells responsible for returning blood cell production to normal. Lymphocytes are the white blood cells that can cause GVHD. The technique requires two steps. In the first step blood cells are collected from donors who have received doses of a growth factor. The growth factor (granulocyte colony stimulating factor) is designed to increase the production of donor stem cells. In the second step white blood cell lymphocytes are removed from the collected blood, leaving only the stem cells. The main goal of this study is to develop and improve the method of processing cells that are collected after stimulation with growth factor (G-CSF), by removing the white blood cell lymphocytes which can cause graft-versus-host disease (GVHD) while keeping the stem cells necessary for healthy blood cell building. In addition, researchers are interested in studying whether giving G-CSF has an effect on lymphocyte function, which may influence the immune reactions occurring in bone marrow transplantation.
Detailed Description The NHLBI Hematology Branch Stem Cell Transplantation program is exploring ways to make allogeneic transplantation safer and more widely applicable. Prior Hematology Branch transplant protocols have evaluated the strategy of using T cell depleted marrow transplants followed by delayed lymphocyte add-back to control or prevent GVHD while conserving useful donor immune function against residual leukemia and infectious agents. Over the past ten years, a number of increasingly efficient methods have been used to deplete T cells but retain stem cells, and we have shown the safety and utility of the delayed T cell add-back approach. We have also found a positive relationship between administration of higher CD34+ cell doses and outcome. Investigation of highly purified grafts with add-back of specific T cell populations is ongoing, and the ability to test new purification approaches and devices on clinical-scale PBSC products is critical to the continued development of new transplantation approaches in our program. This requires testing the approaches on G-CSF mobilized PBSCs collected by apheresis from healthy donors, since this is the cell source that will be used in all clinical allogeneic transplantation protocols in our program. Therefore, the primary intent of this protocol is to provide a mechanism for mobilizing, collecting, storing, and analyzing G-CSF mobilized apheresis samples from healthy volunteers. Cells will be used to develop a method of processing the cells that are collected after stimulation with G-CSF, by removing the lymphocytes, which can mediate GVHD while retaining the stem cells which are necessary for hematopoietic reconstitution. At the same time we will study whether G-CSF administration has an effect on the lymphocyte, function which may influence the immune reactions occurring in allogeneic bone marrow transplantation. Furthermore the CD34+ cells collected will be a valuable resource for experimental studies of lymphocyte-stem cell interactions in our laboratory.
Study Phase Phase 1
Study Type † Interventional
Study Design †
Primary Outcome Measure † Enumeration of laboratory studies using collected primitive hematopoietic cells and immune effector cells.
Secondary Outcome Measure †
Condition † Graft vs Host Disease Healthy Lymphopenia
Intervention † DrugG-CSF
Study Arms / Comparison Groups
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 99999999
Start Date † March 12, 1996
Completion Date May 1, 2030
Primary Completion Date May 1, 2026
Eligibility Criteria † - INCLUSION CRITERIA: Healthy healthy individual aged between 18 and 60 years. No active infection or history of recurrent infection. Normal renal function: creatinine less than 1.5 mg/dl, proteinuria less than 1+. Normal liver function: bilirubin less than 1.5 mg/dl, transaminase within normal limit. Normal blood count: WBC 3000 to 10,000/mm(3), granulocytes greater than 1500/mm(3), platelets greater than 150,000/mm(3), hemoglobin greater than 12.5 g/dl, MCV and MCHC normal. Normal cardiovascular function, no history of chest pain, myocardial infarction, peripheral vascular disease, transient ischemic attack, or stroke. Healthy female subjects of childbearing age should have a negative serum pregnancy test within one week of beginning G-CSF administration. Female subjects should not be lactating. Subject must be eligible for normal blood donation. He or she must be tested negative for syphilis (RPR), hepatitis B and C (HBsAg, Anti HBc, Anti HCV), HIV and HTLV 1. Subject must be able to comprehend the investigational nature of the study and provide informed consent to participate in the protocol. Antecubital veins must be adequate for peripheral access during apheresis. Potential participants must be screened by an apheresis nurse to check venous access before protocol entry. EXCLUSION CRITERIA: Active viral, bacterial, fungal or parasite infection. Female with positive pregnancy test or lactating. History of autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus. History of cancer excluding squamous carcinoma of the skin. History of any hematologic disorders. History of cardiovascular disease or related symptoms such as chest pain, shortness of breath, history of cerebrovascular disease. Any positive serum screening test as listed in eligibility. Allergy to G-CSF or bacterial E coli products. Administration of NSAID within 10 days of starting protocol. History of G-CSF administration and leukapheresis within past 3 months.
Gender All
Ages 18 Years - 60 Years
Accepts Healthy Volunteers Accepts Healthy Volunteers
Contacts †† Therese L Intrater, (240) 476-3702,
Location Countries † United States
Administrative Information
NCT ID † NCT00001529
Organization ID 960049
Secondary IDs †† 96-H-0049
Responsible Party
Study Sponsor † National Heart, Lung, and Blood Institute (NHLBI)
Collaborators †† New York University and New York Genome Center
Investigators † Principal Investigator: Andre Larochelle, M.D., National Heart, Lung, and Blood Institute (NHLBI)
Information Provided By
Verification Date May 12, 2017
First Received Date † November 3, 1999
Last Updated Date May 13, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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