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| Sponsored by: |
National Heart, Lung, and Blood Institute (NHLBI) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00001529 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Graft vs Host Disease Healthy Lymphopenia |
Drug: G-CSF |
Phase I |
| Study Type: | Interventional |
| Study Design: | Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study |
| Official Title: | Use of Granulocyte Colony Stimulating Factor (G-CSF) Mobilized Leukapheresis Collections From Normal Volunteers to Develop Improved Methods of Stem Cell and Lymphocyte Selection for Allogeneic Transplantation |
| Study Start Date: | March 1996 |
Two controllable factors, which affect bone marrow transplant outcome are the quality and quantity of the donor's hematopoietic stem cells and lymphocytes given. Recently it has been demonstrated that rapid hematopoietic recovery and improved transplant outcome can be achieved with transplants of growth factor (G-CSF) mobilized peripheral blood stem cells from the donor. This procedure avoids the need for bone marrow harvesting and provides in the region of tenfold greater numbers of stem cells than the bone marrow harvest achieves. However the risk of graft-versus-host disease (GVHD) is not diminished because large numbers of lymphocytes are transfused with the stem cells. In order to optimize the stem cell dose while reducing the risk of GVHD it will be necessary to carry out T-lymphocyte depletion on G-CSF mobilized peripheral blood. This is a technical challenge because of the large numbers of lymphocytes in the donation. To obtain the 4-log lymphocyte depletion required, it will be necessary to use a two step processing method involving positive enrichment of stem cells (CD34+ cells), followed by T lymphocyte depletion of the product. Before using G-CSF mobilized peripheral blood transplants instead of bone marrow transplants we will need to perfect the technique of accurate stem cell and lymphocyte dosing which has not yet been attempted in clinical practice. While developing the technique for clinical use we will also study the effect of G-CSF on lymphocyte subsets and function.
So the primary intent of this protocol is 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.
Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Normal 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.
Normal 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 can participate no more than 3 times. Each time must be at least 3 months apart.
Subject must be able to comprehend the investigational nature of the study and provide informed consent to participate in this 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 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.
Contacts and Locations| Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
| Contact: TTY | 1-866-411-1010 |
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
More Information
| Study ID Numbers: | 960049, 96-H-0049 |
| Study First Received: | November 3, 1999 |
| Last Updated: | July 18, 2008 |
| ClinicalTrials.gov Identifier: | NCT00001529 |
| Health Authority: | United States: Federal Government |
|
G-CSF Donor Apheresis Graft vs. Host Disease Graft-Versus-Leukemia |
Dexamethasone Transient Lymphopenia Improved T-Cell Depletion Normal Volunteer |
|
Dexamethasone Leukemia Graft versus host disease Hematologic Diseases Lymphopenia Graft vs Host Disease |
Leukocyte Disorders Healthy Leukopenia Dexamethasone acetate Immunologic Deficiency Syndromes Homologous wasting disease |
|
Immune System Diseases |
