Ignite Creation Date:
2024-05-06 @ 12:20 AM
Last Modification Date:
2024-10-26 @ 10:48 AM
Study NCT ID:
NCT01555359
Status:
UNKNOWN
Last Update Posted:
2012-03-15
First Post:
2012-03-13
Brief Title:
Telomerase Activity as a Marker For Mobilization Quality
Sponsor:
Rabin Medical Center
Organization:
Rabin Medical Center
Study Overview
Official Title:
Telomerase Activity Of CD34 Cells - Marker For Mobilization Quality And Predictor For Engraftment After Autologous Hematopoietic Cell Transplantation
Status:
UNKNOWN
Status Verified Date:
2012-01
Last Known Status:
RECRUITING
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:
Autologous hematopoietic cell transplantation HCT is a treatment strategy used as advanced line therapy for different malignancies mainly hematological Its main advantage lies in the ability to provide hematologic and immune rescue after high dose chemotherapy therapy The first requirement of a successful transplantation is recruitment of sufficient amount of cells This is achieved by mobilizing CD34 stem cells from the bone marrow to the peripheral blood by G-CSF priming and then harvesting the cells from the peripheral blood at the right timing by means of apheresis Currently the decision on the optimal collection timing is based on the pre-collection CD34 cells blood concentrations
The investigators goal is to investigate whether telomerase the telomere elongation enzyme which constitutionally and solely expressed in progenitor cells is correlated with collection and post HCT engraftment characteristics
The investigators will collect blood from patients when starting GCSF and on the day of planned apheresis Pearson correlation test will be used to correlate between telomerase activity in the samples and with collection and engraftment characteristics
The investigators goal is to investigate whether telomerase the telomere elongation enzyme which constitutionally and solely expressed in progenitor cells is correlated with collection and post HCT engraftment characteristics
The investigators will collect blood from patients when starting GCSF and on the day of planned apheresis Pearson correlation test will be used to correlate between telomerase activity in the samples and with collection and engraftment characteristics
Detailed Description:
Autologous hematopoietic cell transplantation HCT has revolutionized the curative approach to a number of malignancies by providing hematopoietic and immune rescue after high dose cytoreductive therapy In cases of residual disease patients are usually treated with chemotherapy to repress the disease thereafter G-CSF injections are given serially to encourage stem cell proliferation in the bone marrow and mobilization of the stemprogenitor cells to the peripheral blood Another approach usually utilizes in myeloma patients is the administration of G-CSF in steady state without administration of chemotherapy and consequently collection of the CD34 cells
The minimum number of CD34 cells threshold requires for HCT is currently defined as 2 x 106kg However the optimal dose in terms of engraftment may be even higher 5x106kg especially when platelet recovery is considered
In clinical practice the right timing for collection is decided upon measurement of CD34 a membrane glycoprotein of progenitors and stem-cells CD34 levels are measured in the expected maximal effect of the G-CSF priming and accordingly the collection is scheduled Practically if the circulating CD34cell count is 20μL 90 of collections performed the following day would be expected to yield 20x106 CD34cellskg Gordon BMT 1997 However in cases higher doses of CD34 cells are required eg for tandem HCT CD34 threshold may not be sufficient to determined collection yield
G-CSF based mobilization regimens have a 5-30 failure rate amongst patients however in patients with risk factors up to 60 of the patients are failed to mobilize Poor mobilization has significant consequences for the patient with potential loss of transplantation as a treatment option Repeated attempts at mobilization increase resource utilization morbidity and patient inconvenience Therefore attempts to identify patients who would mobilize poorly are of clinical significance
Human telomerase a unique ribonucleoprotein complex is inactive in normal somatic cells but present in high levels in more than 90 of all malignancies The enzyme synthesize new telomeric repeats at the 3 ends of chromosomes
As oppose to other normal cells stem cells are unique in that they carry active telomerase which provides them with longer life span Previous study from our lab showed that in patients and healthy donors the administration of GCSF was associated with a 14th fold increase of telomerase activity levels in peripheral blood CD34 cells
Working hypothesis
Telomerase activity in mobilized stem cells is correlated with both the absolute number of the collected cells and with the quality of the future engraftment after high dose therapy and HCT
Specific aims
1 To investigate the correlation between telomerase activity of CD34 cells in the day of collection and the total number of collected CD34 cells in a cohort of 50 patients undergoing stem cells mobilization and collection
2 To explore the association between telomerase activity of CD34 cells and the engraftment characteristics time to platelets50000microL time to platelets150000microL time to neutrophils500microL time to neutrophil2000microL
3 To develop an algorithm based on CD34 cells levels and CD34 telomerase activity both measured on the day of collection that can serve as predictor for the total number of CD34 cells to be collected
The minimum number of CD34 cells threshold requires for HCT is currently defined as 2 x 106kg However the optimal dose in terms of engraftment may be even higher 5x106kg especially when platelet recovery is considered
In clinical practice the right timing for collection is decided upon measurement of CD34 a membrane glycoprotein of progenitors and stem-cells CD34 levels are measured in the expected maximal effect of the G-CSF priming and accordingly the collection is scheduled Practically if the circulating CD34cell count is 20μL 90 of collections performed the following day would be expected to yield 20x106 CD34cellskg Gordon BMT 1997 However in cases higher doses of CD34 cells are required eg for tandem HCT CD34 threshold may not be sufficient to determined collection yield
G-CSF based mobilization regimens have a 5-30 failure rate amongst patients however in patients with risk factors up to 60 of the patients are failed to mobilize Poor mobilization has significant consequences for the patient with potential loss of transplantation as a treatment option Repeated attempts at mobilization increase resource utilization morbidity and patient inconvenience Therefore attempts to identify patients who would mobilize poorly are of clinical significance
Human telomerase a unique ribonucleoprotein complex is inactive in normal somatic cells but present in high levels in more than 90 of all malignancies The enzyme synthesize new telomeric repeats at the 3 ends of chromosomes
As oppose to other normal cells stem cells are unique in that they carry active telomerase which provides them with longer life span Previous study from our lab showed that in patients and healthy donors the administration of GCSF was associated with a 14th fold increase of telomerase activity levels in peripheral blood CD34 cells
Working hypothesis
Telomerase activity in mobilized stem cells is correlated with both the absolute number of the collected cells and with the quality of the future engraftment after high dose therapy and HCT
Specific aims
1 To investigate the correlation between telomerase activity of CD34 cells in the day of collection and the total number of collected CD34 cells in a cohort of 50 patients undergoing stem cells mobilization and collection
2 To explore the association between telomerase activity of CD34 cells and the engraftment characteristics time to platelets50000microL time to platelets150000microL time to neutrophils500microL time to neutrophil2000microL
3 To develop an algorithm based on CD34 cells levels and CD34 telomerase activity both measured on the day of collection that can serve as predictor for the total number of CD34 cells to be collected
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