Collection of Peripheral Blood Stem Cells Using G-CSF and Plerixafor in Normal Volunteers

Normal Physiology Clinical Trial

Official title:

Collection of Peripheral Blood Stem Cells Using G-CSF and Plerixafor in Healthy Volunteers

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01123499
• Other study ID #: 100095
• Secondary ID: 10-I-0095
• Status: Terminated
• Start date: October 6, 2016
• Est. completion date: April 28, 2022

Study information

• Verified date: May 2021
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: - Many treatments for immune system disorders involve the use of stem cells that have been collected from blood marrow. To obtain these stem cells without surgery, individuals receive granulocyte colony-stimulating factor (G-CSF) to encourage the production of stem cells that can be collected through blood donations. However, not all patients or normal donors respond to G-CSF alone. - Plerixafor, recently approved by the Food and Drug Administration, is different from G-CSF but also allows stem cells to be collected from donated blood. However, more research is needed on the quality and viability of the stem cells collected after using both G-CSF and plerixafor. Objectives: - To collect and study the blood cells produced after treatment with G-CSF and plerixafor in healthy volunteers. Eligibility: - Healthy volunteers between 18 and 65 years of age who are eligible to donate blood. Design: - Participants will be screened with a medical history, physical examination, and initial blood tests. - At the start of the study cycle, participants will receive daily morning injections of G-CSF for 5 days. These may be given at the clinical center or by the participant after teaching, depending on the participant s preference. - On the morning of Day 4, participants will visit the clinical center to provide a blood sample after the injection. On the evening of Day 4, participants will receive an injection of plerixafor. - Participants will have the final injection of G-CSF on the morning of Day 5, and will provide another blood sample. - On Day 5, participants will have apheresis to separate the stem cells from the rest of the blood. The apheresis may take up to 5 hours to complete. - The study will end after a follow-up phone call 7 to 14 days after the apheresis procedure.

Description:

Hematopoietic stem cells that have been mobilized from the bone marrow into the peripheral circulation are readily collected by apheresis, and may be used for several purposes. They are used for allogeneic and autologous transplantation and are often manipulated in various ways depending on the goal of the transplant. Gene therapy for immunodeficiencies relies on the collection of these cells. Traditionally, mobilization has been done using granulocyte colony stimulating factor (G-CSF). However not all patients or normal donors respond to GCSF alone. Plerixafor, a recently Food and Drug Administration (FDA) approved drug, has a unique mode of action distinct from that of GCSF, but also results in mobilization of peripheral blood progenitors into the circulation, allowing their collection by standard apheresis. The quality of these cells for transduction using viral vectors in anticipation of gene therapy uses has not been thoroughly assessed, and there are theoretical considerations why vectors that use various envelopes for cell binding may be affected by the use of this CXCR4 antagonist. In order to be able to assess the transduction and engraftment of these cells in murine models, we will perform collection and mobilization on 5 healthy volunteers at the NIH Clinical Center using the FDA approved medications G-CSF and plerixafor.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: April 28, 2022
• Est. primary completion date: January 27, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

• INCLUSION CRITERIA:

To be eligible to participate in this study, a subject must satisfy all of the following

criteria:

1. The subject must be a healthy adult aged 18-65 years, and weighing at least 50 kg. 2, The subject must have normal renal function (creatinine <1.5 mg/dL; <1 plus proteinuria); normal hepatic function (bilirubin < 1.5 mg/dL); normal hematologic function (WBC greater than or equal to 2500/mm(3); granulocytes greater than or equal to 1200/mm(3); platelets greater than or equal to 120,000; hematocrit greater than or equal to 38).

3. A female of childbearing potential may be entered if she is using 1 or 2 forms of effective contraception (depending on the type of contraception), and has a negative serum pregnancy test within 1 week of beginning G-CSF administration. She must continue with the effective contraception 3 months after receiving plerixafor

4. The subject must be willing to allow blood cell samples to be stored. EXCLUSION CRITERIA: A subject will be ineligible to participate in this study if any of the following criteria

are met:

1. The subject has a temperature > 38 degrees Celsius, or WBC > 9000/mm(3).

2. A female who is pregnant or lactating as determined by history and/or pregnancy test.

3. The subject has a history of vasculitis, uncontrolled hypertension, or symptomatic coronary artery disease, or similar disorders.

4. The subject has a positive test result for any of the following: human immunodeficiency virus (HIV) I & II antibody, hepatitis C virus (HCV) antibody, hepatitis B soluble antigen (HBSAg), or the rapid plasma reagin (RPR) test for syphilis.

5. The subject lacks peripheral venous access in arm veins adequate for apheresis.

6. The subject is currently participating in other research studies.

7. The subject may be excluded at the discretion of the Principal Investigator (PI).

Related Conditions & MeSH terms

• Normal Physiology

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Flomenberg N, Devine SM, Dipersio JF, Liesveld JL, McCarty JM, Rowley SD, Vesole DH, Badel K, Calandra G. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood. 2005 Sep 1;106(5):1867-74. Epub 2005 May 12. — View Citation

Lévesque JP, Hendy J, Takamatsu Y, Simmons PJ, Bendall LJ. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest. 2003 Jan;111(2):187-96. — View Citation

Liles WC, Broxmeyer HE, Rodger E, Wood B, Hübel K, Cooper S, Hangoc G, Bridger GJ, Henson GW, Calandra G, Dale DC. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood. 2003 Oct 15;102(8):2728-30. Epub 2003 Jul 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Apheresis	To collect cells from normal volunteers using both G-CSF and plerixafor, to be able to use these in various research applications.	Time of Apheresis
Secondary	Apheresis	To characterize the grafts obtained from normal donors using G-CSF and plerixafor and to compare these grafts to historical grafts collected using G-CSF alone.	6 months after collect of cells

External Links

•   NIH Clinical Center Detailed Web Page