Ignite Creation Date:
2024-05-05 @ 11:34 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00075335
Status:
COMPLETED
Last Update Posted:
2018-02-07
First Post:
2004-01-08
Brief Title:
AMD 3100 Mozobil Plerixafor to Mobilize Stem Cells for Donation
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Peripheral Blood Hematopoietic Progenitor Cell Mobilization With AMD 3100 Mozobil in Healthy Volunteers Previously Mobilized With G-CSF
Status:
COMPLETED
Status Verified Date:
2018-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Peripheral blood progenitor cells PBPC have become the preferred source of hematopoetic stem cells for allogeneic transplantation because of technical ease of collection and shorter time required for engraftment Traditionally granulocyte-colony stimulating factor G-CSF has been used to procure the peripheral blood stem cell graft Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors 5-10 will mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow harvesting Although G-CSF is generally well tolerated in healthy donors it may be associated with bone pain headache myalgia and rarely life threatening side effects like stroke myocardial infarction and splenic rupture
AMD3100 is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 SDF-1 to its cognate receptor CXC- chemokine receptor 4 CXCR4 CXCR4 is present on cluster of differentiation 34 CD34 hematopoetic progenitor cells and its interaction with stromal cell derived factor 1 SDF-1 plays a pivotal role in the homing of CD34 cells in the bone marrow Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34 cells into the circulation which can then be collected easily by apheresis
Recently a published report demonstrated that large numbers of CD34 cells were rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100 Remarkably the number of CD34 cells collected by apheresis following a single injection of AMD3100 was comparable to the number of CD34 cells collected from historical controls receiving 5 days of G-CSF prior to stem cell mobilization
In this study we will collect PBPCs following a single subcutaneous injection of AMD3100 from healthy donors who have previously had PBPC collected using standard G-CSF mobilization The AMD3100 mobilized cells G-CSF mobilized cells and circulating cells prior to both AMD3100 and G-CSF mobilization will be analyzed in terms of cellular content and function of lymphocytes natural killer NK cells and antigen presenting cells AMD3100 mobilized PBPC will be collected for the purpose of research studies and will not be used for therapeutic purposes
AMD3100 is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 SDF-1 to its cognate receptor CXC- chemokine receptor 4 CXCR4 CXCR4 is present on cluster of differentiation 34 CD34 hematopoetic progenitor cells and its interaction with stromal cell derived factor 1 SDF-1 plays a pivotal role in the homing of CD34 cells in the bone marrow Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34 cells into the circulation which can then be collected easily by apheresis
Recently a published report demonstrated that large numbers of CD34 cells were rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100 Remarkably the number of CD34 cells collected by apheresis following a single injection of AMD3100 was comparable to the number of CD34 cells collected from historical controls receiving 5 days of G-CSF prior to stem cell mobilization
In this study we will collect PBPCs following a single subcutaneous injection of AMD3100 from healthy donors who have previously had PBPC collected using standard G-CSF mobilization The AMD3100 mobilized cells G-CSF mobilized cells and circulating cells prior to both AMD3100 and G-CSF mobilization will be analyzed in terms of cellular content and function of lymphocytes natural killer NK cells and antigen presenting cells AMD3100 mobilized PBPC will be collected for the purpose of research studies and will not be used for therapeutic purposes
Detailed Description:
Peripheral blood progenitor cells PBPC have become the preferred source of hematopoietic stem cells for allogeneic transplantation because of technical ease of collection and shorter time required for engraftment Traditionally granulocyte-colony stimulating factor G-CSF has been used to procure the peripheral blood stem cell graft Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors 5-10 will mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow harvesting Although G-CSF is generally well tolerated in healthy donors it may be associated with bone pain headache myalgia and rarely life threatening side effects like stroke myocardial infarction and splenic rupture
AMD3100 is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 SDF-1 to its cognate receptor CXCR4 CXCR4 is present on CD34 hematopoietic progenitor cells and its interaction with SDF-1 plays a pivotal role in the homing of CD34 cells in the bone marrow Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34 cells into the circulation which can then be collected easily by apheresis Recently a published report demonstrated that large numbers of CD34 cells were rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100 Remarkably the number of CD34 cells collected by apheresis following a single injection of AMD3100 was comparable to the number of CD34 cells collected from historical controls receiving 5 days of G-CSF prior to stem cell mobilization Although the study population is relatively small side-effects to this agent have been mild and transient with no serious complications having been reported The ability to collect a large quantity of PBPC with a single injection of this drug makes this an attractive agent for mobilizing donors of allogeneic PBPC However the immunologic profiles of AMD3100 mobilized cells in terms of lymphocyte content T cell B cell NK cell immuno-regulatory T cell T cell polarization status TH1 versus TH2 status of antigen presenting cells DC1 versus DC2 alloreactive potential and preservation of reactivity to infectious agents eg Epstein Barr Virus EBV Cytomegalovirus CMV are unknown Consequently whether AMD3100 mobilized PBPC would be suitable for use as an allograft is uncertain In this study we will collect PBPCs following a single subcutaneous injection of AMD3100 from healthy donors who have previously had PBPC collected using standard G-CSF mobilization The AMD3100 mobilized cells G-CSF mobilized cells and circulating cells prior to both AMD3100 and G-CSF mobilization will be analyzed in terms of cellular content and function of lymphocytes NK cells and antigen presenting cells AMD3100 mobilized PBPC will be collected for the purpose of research studies and will not be used for therapeutic purposes
The primary objective is to characterize the immunological properties of AMD3100 mobilized cytokine gene expression profiles T-cells compared to G-CSF mobilized T-cells
Secondary endpoints include the cellular content and other immune properties of AMD3100 mobilized cells yields of hematopoietic progenitor cells immune cells and other cellular subsets collected by apheresis in subjects undergoing G-CSF and AMD3100 mobilization and the safety profile of AMD3100
AMD3100 is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 SDF-1 to its cognate receptor CXCR4 CXCR4 is present on CD34 hematopoietic progenitor cells and its interaction with SDF-1 plays a pivotal role in the homing of CD34 cells in the bone marrow Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34 cells into the circulation which can then be collected easily by apheresis Recently a published report demonstrated that large numbers of CD34 cells were rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100 Remarkably the number of CD34 cells collected by apheresis following a single injection of AMD3100 was comparable to the number of CD34 cells collected from historical controls receiving 5 days of G-CSF prior to stem cell mobilization Although the study population is relatively small side-effects to this agent have been mild and transient with no serious complications having been reported The ability to collect a large quantity of PBPC with a single injection of this drug makes this an attractive agent for mobilizing donors of allogeneic PBPC However the immunologic profiles of AMD3100 mobilized cells in terms of lymphocyte content T cell B cell NK cell immuno-regulatory T cell T cell polarization status TH1 versus TH2 status of antigen presenting cells DC1 versus DC2 alloreactive potential and preservation of reactivity to infectious agents eg Epstein Barr Virus EBV Cytomegalovirus CMV are unknown Consequently whether AMD3100 mobilized PBPC would be suitable for use as an allograft is uncertain In this study we will collect PBPCs following a single subcutaneous injection of AMD3100 from healthy donors who have previously had PBPC collected using standard G-CSF mobilization The AMD3100 mobilized cells G-CSF mobilized cells and circulating cells prior to both AMD3100 and G-CSF mobilization will be analyzed in terms of cellular content and function of lymphocytes NK cells and antigen presenting cells AMD3100 mobilized PBPC will be collected for the purpose of research studies and will not be used for therapeutic purposes
The primary objective is to characterize the immunological properties of AMD3100 mobilized cytokine gene expression profiles T-cells compared to G-CSF mobilized T-cells
Secondary endpoints include the cellular content and other immune properties of AMD3100 mobilized cells yields of hematopoietic progenitor cells immune cells and other cellular subsets collected by apheresis in subjects undergoing G-CSF and AMD3100 mobilization and the safety profile of AMD3100
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-H-0078 | OTHER | NIH NHLBI | None |