Telomerase Activity as a Marker For Mobilization Quality
Recruitment status was Recruiting
|First Received Date ICMJE||March 13, 2012|
|Last Updated Date||March 14, 2012|
|Start Date ICMJE||February 2012|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01555359 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Telomerase Activity as a Marker For Mobilization Quality|
|Official Title ICMJE||Telomerase Activity Of CD34+ Cells - Marker For Mobilization Quality And Predictor For Engraftment After Autologous Hematopoietic Cell Transplantation|
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.
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 stem/progenitor 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 10^6/kg. However, the optimal dose in terms of engraftment may be even higher (>5x10^6/kg), 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 CD34+cell count is ≥20/μL, 90% of collections performed the following day would be expected to yield ≥2.0x106 CD34+cells/kg (Gordon, BMT 1997). However, in cases higher doses of CD34+ cells are required (e.g. 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.
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
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Biospecimen||Retention: Samples Without DNA
|Sampling Method||Non-Probability Sample|
Patients undergoing stem cell mobilization and collection
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Patients undergoing stem cell collection|
|Publications *||Szyper-Kravitz M, Uziel O, Shapiro H, Radnay J, Katz T, Rowe JM, Lishner M, Lahav M. Granulocyte colony-stimulating factor administration upregulates telomerase activity in CD34+ haematopoietic cells and may prevent telomere attrition after chemotherapy. Br J Haematol. 2003 Jan;120(2):329-36.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||50|
|Estimated Completion Date||February 2013|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 75 Years|
|Accepts Healthy Volunteers||No|
|Listed Location Countries ICMJE||Israel|
|Removed Location Countries|
|NCT Number ICMJE||NCT01555359|
|Other Study ID Numbers ICMJE||HCT-TEL-001|
|Has Data Monitoring Committee||No|
|Responsible Party||Rabin Medical Center|
|Study Sponsor ICMJE||Rabin Medical Center|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Rabin Medical Center|
|Verification Date||January 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP