Ignite Creation Date:
2024-05-05 @ 4:51 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00322127
Status:
COMPLETED
Last Update Posted:
2020-10-08
First Post:
2006-05-04
Brief Title:
An Evaluation of Safety and Efficacy of Escalating Doses of AMD3100 to Mobilize CD34 Cells in Healthy Volunteers
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Study of the Safety and Activity of Escalating Doses of AMD3100 to Mobilize CD34 Cells in Healthy Volunteers
Status:
COMPLETED
Status Verified Date:
2020-10
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:
This study will determine how safely and well people can tolerate AMD3100 at larger than normal doses to mobilize CD34 cells stem cells AMD3100 is a new drug designed to mobilize stem cells for transplantation in cancer patients It pushes those cells into the circulation making it easier to collect them and it temporarily increases the number of stem cells in a persons blood
Patients ages 18 to 50 in good health and who are not pregnant or breastfeeding may be eligible for this study They will undergo the following tests and procedures
History and physical examination
Review of medications including those prescribed and over-the-counter as well as nutritional supplements
Blood tests for liver kidneys and other functions and for infections including hepatitis and AIDS
Pregnancy test
Electrocardiogram
On the day they receive AMD3100 patients will be admitted to the Clinical Center They will receive two doses injected under the skin at intervals separated by 14 to 90 days Dose levels are 240 and 320 microgramskg and 400 and 480 microgramskg For 24 hours following the first AMD3100 administration blood will be collected periodically through a plastic tube at amounts dependent on doses of AMD3100 given If patients receive one of the two highest doses their heart rhythm will be monitored continuously during the hospital stay From 7 to 10 days following administration of AMD3100 patients will give blood samples to monitor the effects The second dose of AMD3100 will be given 14 to 90 days after the first one Patients will return to the Clinical Center for the same procedures as done previously but the dose of the drug will be higher
Risks involve side effects of AMD3100 In previous studies patients who received the drug experienced a temporary increase in white blood cell counts Serious side effects have included abnormally low platelet clot abnormal heart rhythm and low blood pressure Patients will be carefully monitored for such effects
Patients ages 18 to 50 in good health and who are not pregnant or breastfeeding may be eligible for this study They will undergo the following tests and procedures
History and physical examination
Review of medications including those prescribed and over-the-counter as well as nutritional supplements
Blood tests for liver kidneys and other functions and for infections including hepatitis and AIDS
Pregnancy test
Electrocardiogram
On the day they receive AMD3100 patients will be admitted to the Clinical Center They will receive two doses injected under the skin at intervals separated by 14 to 90 days Dose levels are 240 and 320 microgramskg and 400 and 480 microgramskg For 24 hours following the first AMD3100 administration blood will be collected periodically through a plastic tube at amounts dependent on doses of AMD3100 given If patients receive one of the two highest doses their heart rhythm will be monitored continuously during the hospital stay From 7 to 10 days following administration of AMD3100 patients will give blood samples to monitor the effects The second dose of AMD3100 will be given 14 to 90 days after the first one Patients will return to the Clinical Center for the same procedures as done previously but the dose of the drug will be higher
Risks involve side effects of AMD3100 In previous studies patients who received the drug experienced a temporary increase in white blood cell counts Serious side effects have included abnormally low platelet clot abnormal heart rhythm and low blood pressure Patients will be carefully monitored for such effects
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 PBPC graft Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors 5-10 of subjects will mobilize progenitor cells poorly and may require multiple large volume apheresis or bone marrow harvesting
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-SDF-1 axis by AMD3100 releases CD34 cells into the circulation which can then be collected easily by apheresis Recently several reports have demonstrated that large numbers of progenitor CD34 cells are rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100 The ability to collect a large quantity of PBPCs with a single injection of this drug makes this an attractive agent for mobilizing both autologous and allogeneic donors for hematopoietic stem cell transplantation
A phase one dose escalating trial of AMD3100 in healthy donors done outside the NHLBI suggested the peak CD34 mobilizing effects of this agent occurred at the 240 microgramkg dose Of note no dose limiting toxicities were observed at the highest dose level of 320 mcgkg In two current trials at the NHLBI AMD3100 has also proven to be well tolerated at the 240 mcgkg dose however the progenitor CD34 cell yield following a matched volume apheresis was lower compared to G-CSF mobilizations collected from the same healthy volunteers More importantly the number of CD34 cells collected following one dose of AMD3100 has frequently been less than 3 x 106 CD34 cellskg the previously defined minimal dose of progenitor cells required to optimize allogeneic hematopoietic stem cell transplantation outcomes In addition preliminary data from non-human primate studies suggest that higher doses of AMD3100 may improve CD34 cell yield in an apheresis collection
Based on these data it is possible that inter-subject variability in CD34 cell mobilization may have led investigators in the prior phase I study to prematurely terminate AMD3100 dose escalation based on the perception that CD34 doses had peaked We therefore propose this dose escalating study designed to evaluate the safety and activity of AMD3100 when administered in escalating higher doses 240 microgramkg dose 320 microgramkg dose 400 microgramkg dose 480 microgramkg dose Activity will be evaluated by measuring the most effective dose of AMD3100 in mobilizing progenitor CD34 cells into the circulation in healthy donors To minimize inter-subject variability we will administer two different doses of AMD3100 to each subject evaluating the peak CD34 cell count achieved after each dose Separate cohorts of healthy volunteers will be evaluated for each dose escalation The short half life and rapid wash-out of AMD3100 allows for this method of study
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-SDF-1 axis by AMD3100 releases CD34 cells into the circulation which can then be collected easily by apheresis Recently several reports have demonstrated that large numbers of progenitor CD34 cells are rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100 The ability to collect a large quantity of PBPCs with a single injection of this drug makes this an attractive agent for mobilizing both autologous and allogeneic donors for hematopoietic stem cell transplantation
A phase one dose escalating trial of AMD3100 in healthy donors done outside the NHLBI suggested the peak CD34 mobilizing effects of this agent occurred at the 240 microgramkg dose Of note no dose limiting toxicities were observed at the highest dose level of 320 mcgkg In two current trials at the NHLBI AMD3100 has also proven to be well tolerated at the 240 mcgkg dose however the progenitor CD34 cell yield following a matched volume apheresis was lower compared to G-CSF mobilizations collected from the same healthy volunteers More importantly the number of CD34 cells collected following one dose of AMD3100 has frequently been less than 3 x 106 CD34 cellskg the previously defined minimal dose of progenitor cells required to optimize allogeneic hematopoietic stem cell transplantation outcomes In addition preliminary data from non-human primate studies suggest that higher doses of AMD3100 may improve CD34 cell yield in an apheresis collection
Based on these data it is possible that inter-subject variability in CD34 cell mobilization may have led investigators in the prior phase I study to prematurely terminate AMD3100 dose escalation based on the perception that CD34 doses had peaked We therefore propose this dose escalating study designed to evaluate the safety and activity of AMD3100 when administered in escalating higher doses 240 microgramkg dose 320 microgramkg dose 400 microgramkg dose 480 microgramkg dose Activity will be evaluated by measuring the most effective dose of AMD3100 in mobilizing progenitor CD34 cells into the circulation in healthy donors To minimize inter-subject variability we will administer two different doses of AMD3100 to each subject evaluating the peak CD34 cell count achieved after each dose Separate cohorts of healthy volunteers will be evaluated for each dose escalation The short half life and rapid wash-out of AMD3100 allows for this method of study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
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 |
|---|---|---|---|
| 06-H-0156 | None | None | None |