Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives

NCT00001529 | Recruiting

• 2 other identifiers: 96004996-H-0049
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft-Versus-Host Disease; Graft-versus-leukemia; Donor Apheresis

Keywords

G-CSF; Donor Apheresis; Graft Versus Host Disease; graft versus leukemia; Natural History; Normal Volunteer

Outcome Measures

Primary Outcomes (1)

• Provide a source of primitive hematopoietic cells from mobilized blood for laboratory studies including optimization of culture and expansion, preservation techniques, gene transfer, analysis of cell surface antigens, & analysis of migra...

  End of Study

Secondary Outcomes (2)

• Use the cells to develop a reliable technique for T cell depletion of peripheral blood stem cell transplants, which conserves sufficient CD34 cells for safe engraftment while minimizing the risk of GVHD.

• Study the effect of G-CSF on lymphocyte subsets and helper cytotoxic function.

Study Arms (1)

Group 1

Healthy volunteers

Drug: G-CSF

Interventions

G-CSF DRUG

After medical clearance, volunteers will undergo outpatient mobilization with daily subcutaneous injections of filgrastim (G-CSF). The first dose will be administered at the NIH Clinical Center, with one-hour monitoring for immediate reactions. Volunteers may either return to NIH for daily injections or self-administer at home after training.

Group 1

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Healthy Volunteers

You may qualify if:

• Healthy individual aged 18 to 60 years.
• No active infection or history of recurrent infection.
• Normal renal function: creatinine \<1.5 mg/dL or estimated glomerular filtration rate (eGFR) \>=60 mL/min/1.73 m\^2, with no significant proteinuria.
• Normal liver function: bilirubin \<2.0 mg/dL (when unconjugated), transaminases \<2.0x ULN in the absence of known liver disease.
• Normal blood count: WBC 2,500-11,000/microliter, ANC \>1,500/microliter, platelets \>150,000/microliter, hemoglobin \>12.0 g/dL.
• 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 with 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, HTLV-1, West Nile virus, T. Cruzi and Babesia test.
• 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.

You may not qualify if:

• Active viral, bacterial, fungal or parasite infection.
• Female with positive pregnancy test or lactating.
• Active or moderate-to-severe autoimmune disease that is currently treated or expected to require immunosuppressive therapy. Candidates with stable, well-controlled mild autoimmune disease may be considered on a case-by-case basis.
• Active or recent malignancy within the past 5 years. Individuals with remote (\>5 years) histories of low-risk malignancies in remission (e.g., localized prostate cancer) or treated basal cell carcinoma may be included.
• History of any hematologic disorders.
• History of clinically significant cardiovascular disease (e.g., symptomatic coronary artery disease, uncontrolled hypertension). Minor risk factors must be evaluated on a case-by-case basis (e.g., controlled hypertension).
• Any positive serum screening test as listed in eligibility.
• Allergy to G-CSF or bacterial E coli products.
• Administration of NSAID within. 5-7 days of starting the protocol, depending on drug half-life.
• History of G-CSF administration and leukapheresis within past 3 months.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• New York University and New York Genome Center: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• Goldman J. Peripheral blood stem cells for allografting. Blood. 1995 Mar 15;85(6):1413-5. No abstract available.

  PMID: 7534129 BACKGROUND

• Grigg AP, Roberts AW, Raunow H, Houghton S, Layton JE, Boyd AW, McGrath KM, Maher D. Optimizing dose and scheduling of filgrastim (granulocyte colony-stimulating factor) for mobilization and collection of peripheral blood progenitor cells in normal volunteers. Blood. 1995 Dec 15;86(12):4437-45.

  PMID: 8541532 BACKGROUND

• Cottler-Fox M, Cipolone K, Yu M, Berenson R, O'Shaughnessy J, Dunbar C. Positive selection of CD34+ hematopoietic cells using an immunoaffinity column results in T cell-depletion equivalent to elutriation. Exp Hematol. 1995 Apr;23(4):320-2.

  PMID: 7534711 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Andre Larochelle, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard A Gustafson, R.N.

CONTACT

(301) 402-5822; richard.gustafson@nih.gov

Andre Larochelle, M.D.

CONTACT

(301) 451-7139; larochea@nhlbi.nih.gov

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: March 18, 1996
• Last Updated: April 28, 2026

Record last verified: 2026-03-06

Locations

US (1)