Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001529
First received: November 3, 1999
Last updated: August 1, 2014
Last verified: July 2014
  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 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Enumeration of laboratory studies using collected primitive hematopoietic cells and immune effector cells.

Estimated Enrollment: 99999999
Study Start Date: March 1996
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: G-CSF
    N/A
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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001529

Contacts
Contact: Kinneret S Broder (301) 402-2837 broderk@mail.nih.gov
Contact: Andre Larochelle, MD, PhD (301) 451-7139 larochea@nhlbi.nih.gov

Locations
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 Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Andre Larochelle, MD, PhD National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00001529     History of Changes
Other Study ID Numbers: 960049, 96-H-0049
Study First Received: November 3, 1999
Last Updated: August 1, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
G-CSF
Donor Apheresis
Graft vs. Host Disease
Graft-Versus-Leukemia
Dexamethasone
Transient Lymphopenia
Improved T-Cell Depletion
Normal Volunteer

Additional relevant MeSH terms:
Lymphopenia
Graft vs Host Disease
Hematologic Diseases
Immune System Diseases
Immunologic Deficiency Syndromes
Leukocyte Disorders
Leukopenia
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 29, 2014