Ignite Creation Date:
2024-05-05 @ 11:18 PM
Last Modification Date:
2024-10-26 @ 10:32 AM
Study NCT ID:
NCT01306188
Status:
COMPLETED
Last Update Posted:
2015-07-02
First Post:
2011-02-28
Brief Title:
Prognostic Value of Divpenia and CD4 Count in Relapsed Breast or Lung Cancer Patients
Sponsor:
Centre Leon Berard
Organization:
Centre Leon Berard
Study Overview
Official Title:
Study of Prognostic Value of T Cell Receptor Diversity and CD4 Lymphopenia in First Relapse Breast or Lung Cancer Patients
Status:
COMPLETED
Status Verified Date:
2015-07
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:
LYMPHOS1
Brief Summary:
The T and B cells repertoire diversity represent one of the immune defence level which controls the integrity of the organism and determines its ability to recognize and control infectious attacks and development of tumours The study of the lymphocytes TCR and BCR diversity could permit to better understand how lymphopenia act on overall survival and to improve detection of high risk patients who could benefit of adapted therapies for better care
Detailed Description:
The therapeutic management recommendations of patients with metastatic cancer offer standard treatment in specific situations But there is always a subgroup of patients who do not benefit from treatment and which has a very low survival The risk of death for patients is very variable depending on the initial cancer site tumor aggressiveness and chemosensitivity of tumours
Its therefore important to have relevant prognostic tools to predict such an excess of relative toxicity or drug resistance Simple prognostic factors for survival as the performance status PS have already been highlighted in several studies Thus the possibility to identify a group of patients with a higher risk of mortality could be of major interest for clinicians In fact such stratification will allow
To limit this risk by adjusting the therapy andor associated treatments antibiotic prophylaxis dose reduction
To develop protocols for testing innovative strategies specific to this high risk population
The objectives of these innovative protocols would be designed to correct lymphodivpenia
The main objective is to show that T divpenia low TCR combinatorial diversity 30 is a risk factor for early death after chemotherapy early death any death occurring within 3 months lung cancer or within 6 months breast cancer after the start of chemotherapy
The secondary objectives are
To establish that the divpenia factor is independent of clinical and biological prognostic factors PS LDH haemoglobin lymphopenia or ANC to predict a early death
To establish that the prognostic score NDL which will combine in a two-dimensional graph the CD4 count or total lymphocytes count and TCR repertoire diversity will allow a better stratification of lympho-divpenic patients who will benefit from more appropriate treatments
To characterize other circulating markers this could improve the identification of the early death risk phenotypic markers cytokines in combination with the previous settings
Prognostic models have been established in many tumor types at the initial stage or at time of the relapse breast and lung cancers It seems necessary to highlight other clinical and biological prognostic factors that would estimate a lower survival at 6 months whatever the nature or the original site of the tumour
The strong prognostic value of lymphopenia in the early death after chemotherapy or hematologic toxicity of chemotherapy has recently been established in several tumor models 25 of patients with metastatic solid cancers have a systemic immune dysfunction
Further analysis incorporating prior any treatment D0 a systematic phenotypic analysis of lymphocyte subpopulations in the patients blood showed that a significant reduction in the absolute number of peripheral CD4 T cells 450μl was an independent factor risk of early death and febrile neutropenia in patients with solid cancers of different origin lymphoma myeloma sarcoma breast cancer treated with chemotherapy
However early death remains rare events and a more recent study has established that a lymphopenia 1000 lymphocytesµl was an independent prognostic factor for overall survival in patients with solid tumours
Recent studies have shown the importance of combinatorial diversity of T and B lymphocytes repertoire TCRBCR in the efficiency of the immune response against infection
A preliminary analysis of TCR repertoire diversity in a retrospective cohort of patients with metastatic breast cancer demonstrated the independent predictive value of divpenia for overall survival in these patients This research has demonstrated that patients with cancer had a very large disparity in immune TCR diversity and that it was not always correlated with lymphocyte count
These preliminary data show that the discriminating power of TCR diversity is greater than the measurement of cell count The combined analysis of these data in a NDL graph may help to better discriminate patients at risk for which it is necessary to develop new therapeutic strategies
Its therefore important to have relevant prognostic tools to predict such an excess of relative toxicity or drug resistance Simple prognostic factors for survival as the performance status PS have already been highlighted in several studies Thus the possibility to identify a group of patients with a higher risk of mortality could be of major interest for clinicians In fact such stratification will allow
To limit this risk by adjusting the therapy andor associated treatments antibiotic prophylaxis dose reduction
To develop protocols for testing innovative strategies specific to this high risk population
The objectives of these innovative protocols would be designed to correct lymphodivpenia
The main objective is to show that T divpenia low TCR combinatorial diversity 30 is a risk factor for early death after chemotherapy early death any death occurring within 3 months lung cancer or within 6 months breast cancer after the start of chemotherapy
The secondary objectives are
To establish that the divpenia factor is independent of clinical and biological prognostic factors PS LDH haemoglobin lymphopenia or ANC to predict a early death
To establish that the prognostic score NDL which will combine in a two-dimensional graph the CD4 count or total lymphocytes count and TCR repertoire diversity will allow a better stratification of lympho-divpenic patients who will benefit from more appropriate treatments
To characterize other circulating markers this could improve the identification of the early death risk phenotypic markers cytokines in combination with the previous settings
Prognostic models have been established in many tumor types at the initial stage or at time of the relapse breast and lung cancers It seems necessary to highlight other clinical and biological prognostic factors that would estimate a lower survival at 6 months whatever the nature or the original site of the tumour
The strong prognostic value of lymphopenia in the early death after chemotherapy or hematologic toxicity of chemotherapy has recently been established in several tumor models 25 of patients with metastatic solid cancers have a systemic immune dysfunction
Further analysis incorporating prior any treatment D0 a systematic phenotypic analysis of lymphocyte subpopulations in the patients blood showed that a significant reduction in the absolute number of peripheral CD4 T cells 450μl was an independent factor risk of early death and febrile neutropenia in patients with solid cancers of different origin lymphoma myeloma sarcoma breast cancer treated with chemotherapy
However early death remains rare events and a more recent study has established that a lymphopenia 1000 lymphocytesµl was an independent prognostic factor for overall survival in patients with solid tumours
Recent studies have shown the importance of combinatorial diversity of T and B lymphocytes repertoire TCRBCR in the efficiency of the immune response against infection
A preliminary analysis of TCR repertoire diversity in a retrospective cohort of patients with metastatic breast cancer demonstrated the independent predictive value of divpenia for overall survival in these patients This research has demonstrated that patients with cancer had a very large disparity in immune TCR diversity and that it was not always correlated with lymphocyte count
These preliminary data show that the discriminating power of TCR diversity is greater than the measurement of cell count The combined analysis of these data in a NDL graph may help to better discriminate patients at risk for which it is necessary to develop new therapeutic strategies
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