Breast CancerLYMPHOS1NCT01306188
Prognostic Value of Divpenia and CD4 Count in Relapsed Breast or Lung Cancer Patients
An observational study of Breast Cancer and Lung Cancer, run by Centre Leon Berard at 4 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Lung Cancer
- What is being tested?
- Breast cancer cohort and Lung cancer cohort
- How many people
- 179 participants
- Where
- 4 sitesFrance
- Study dates
- Jul 2010to Dec 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 2 cohorts of patients (breast and lung cancer), with locally advanced or metastatic cancer
Who may be able to join
- Age ≥ 18 years old,
- Patients with an histologically proven, inoperable breast or lung tumour,
- Metastatic disease before the start of any chemotherapy,
- Signed written informed consent form,
- Covered by a medical insurance,
- Patient accepting the conservation of biological samples,
- Locally advanced incurable disease (only breast tumour).
Who cannot join
- Hematological tumour,
- Auto-immune disease (including HIV-positive - AIDS stage) or patients with immunosuppressive therapy,
- Metastatic disease that had progressed after a first line chemotherapy,
- Pregnant or lactating female or female of child-bearing potential not employing adequate contraception,
- Patient deprived of liberty by a judicial or administrative,
- Adult protected by law.
Trial locations and contacts
4 sites in 1 country.
France4 sites
Hopital de la Croix Rousse
Lyon, 69004
Centre Léon Bérard
Lyon, 69008
Hopital Privé Jean Mermoz
Lyon, 69008
CHLS
Pierre-Bénite, 69495
About this study
Official title: Study of Prognostic Value of T Cell Receptor Diversity and CD4 Lymphopenia in First Relapse Breast or Lung Cancer Patients
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.
Read the 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.
It's 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 and/or 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 (<450/μl) 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 lymphocytes/µl) 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 (TCR/BCR) 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.
- Conditions
- Breast Cancer, Lung Cancer
- Being tested
- Breast cancer cohort, Lung cancer cohort
- Keywords
- metastatic cancer, lymphopenia, T cell receptor diversity
- Medical subject headings
- Breast Neoplasms, Lung Neoplasms, Neoplasm Metastasis, Lymphopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Breast cancer cohortBiological
Blood samples must be made within 48 hours after the inclusion of the patient. Patients are treated according to the standards of the centre where they are supported. No follow-up is provided in this study.
For each patient, the following analyses is performed:
- The analysis of TCR and BCR repertoire diversity,
- The phenotypic analysis of immune subpopulations,
- The analysis of the global lymphopenia or subpopulations T,
- The analyses by multiplex assay of a large panel of plasma cytokines and chemokines.
Lung cancer cohortBiological
Blood samples must be made within 48 hours after the inclusion of the patient. Patients are treated according to the standards of the centre where they are supported. No follow-up is provided in this study.
For each patient, the following analyses is performed:
- The analysis of TCR and BCR repertoire diversity,
- The phenotypic analysis of immune subpopulations,
- The analysis of the global lymphopenia or subpopulations T,
- The analyses by multiplex assay of a large panel of plasma cytokines and chemokines.
| Study group | Role | What they receive |
|---|---|---|
| Breast cancer | Metastatic breast cancer Receives: Biological: Breast cancer cohort | |
| Lung cancer | Metastatic lung cancer Receives: Biological: Lung cancer cohort |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analyse the prognostic value of divpenia
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).
Measured: 3 month (lung cancer) 6 month (breast cancer)
Secondary outcomes (3)
Analyse prognostic value of clinico-biological parameters (PS ECOG, LDH levels, - To establish that the divpenia factor is independent of clinical and biological prognostic factors (PS, LDH, metastasis localization, Hb, PMN, age, sex)
Establish that the divpenia factor is independent of clinical and biological prognostic factors (PS, LDH, initial metastasis localization, Hb, PMN, age, sex) to predict a early death,
Measured: 3 month (lung cancer) - 6 month (breast cancer)
Prognostic score NDL
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
Measured: 3 month (lung cancer) - 6 month (breast cancer)
Characterization of other circulating markers
Characterize other circulating markers this could improve the identification of the early death risk (phenotypic markers, cytokines ...) in combination with the previous settings
Measured: 3 month (lung cancer) - 6 month (breast cancer)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2011 (estimated)
- Study startJul 2010
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Centre Leon BerardThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 179 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Leon Berard
- Sponsor type
- University, hospital or other
- Collaborators
- The Biostatistics and Therapy Evaluation Unit, BEC (Department of Clinical Sciences)
- Responsible party
- Sponsor
- Investigators
- Olivier TREDAN, MD, Principal investigator, Centre Leon Berard
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01306188
- Sponsor's protocol ID
- LYMPHOS1
- Acronym
- LYMPHOS1
- Status last verified
- Jul 2015
- First submitted
- 28 Feb 2011
- Last updated
- 2 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Belbaraka R, Tredan O, Ray-Coquard I, Chvetzoff G, Bajard A, Perol D, Ismaili N, Ismaili M, Errihani H, Bachelot T, Rebattu P. Factors of interrupting chemotherapy in patients with Advanced Non-Small-Cell Lung Cancer. BMC Res Notes. 2010 Jun 10;3:164. doi: 10.1186/1756-0500-3-164.
PubMed 20537187Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, Tredan O, Verweij J, Biron P, Labidi I, Guastalla JP, Bachelot T, Perol D, Chabaud S, Hogendoorn PC, Cassier P, Dufresne A, Blay JY; European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009 Jul 1;69(13):5383-91. doi: 10.1158/0008-5472.CAN-08-3845. Epub 2009 Jun 23.
PubMed 19549917
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Prognostic Value of T Cell Receptor Diversity and CD4 Lymphopenia in First Relapse Breast or Lung Cancer Patients
- ClinicalTrials.gov ID
- NCT01306188
- Acronym / sponsor ID
- LYMPHOS1 / LYMPHOS1
- Conditions
- Breast Cancer, Lung Cancer
- Keywords
- metastatic cancer, lymphopenia, T cell receptor diversity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 179 participants (actual)
- Lead sponsor
- Centre Leon BerardUniversity, hospital or other
- Collaborators
- The Biostatistics and Therapy Evaluation Unit, BEC (Department of Clinical Sciences)
- Study start
- Jul 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 1 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
It's 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 and/or 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 (<450/μl) 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 lymphocytes/µl) 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 (TCR/BCR) 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Breast cancer | – | Biological: Breast cancer cohortMetastatic breast cancer |
| Lung cancer | – | Biological: Lung cancer cohortMetastatic lung cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 2 cohorts of patients (breast and lung cancer), with locally advanced or metastatic cancer
Key inclusion criteria (7 listed)
- Age ≥ 18 years old,
- Patients with an histologically proven, inoperable breast or lung tumour,
- Metastatic disease before the start of any chemotherapy,
- Signed written informed consent form,
- Covered by a medical insurance,
Key exclusion criteria (6 listed)
- Hematological tumour,
- Auto-immune disease (including HIV-positive - AIDS stage) or patients with immunosuppressive therapy,
- Metastatic disease that had progressed after a first line chemotherapy,
- Pregnant or lactating female or female of child-bearing potential not employing adequate contraception,
- Patient deprived of liberty by a judicial or administrative,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Breast cancer cohortBlood samples must be made within 48 hours after the inclusion of the patient. Patients are treated according to the standards of the centre where they are supported. No follow-up is provided in this study. For each patient, the following analyses is performed: * The analysis of TCR and BCR repertoire diversity, * The phenotypic analysis of immune subpopulations, * The analysis of the global lymphopenia or subpopulations T, * The analyses by multiplex assay of a large panel of plasma cytokines and chemokines. | Biological | Breast cancer |
| Lung cancer cohortBlood samples must be made within 48 hours after the inclusion of the patient. Patients are treated according to the standards of the centre where they are supported. No follow-up is provided in this study. For each patient, the following analyses is performed: * The analysis of TCR and BCR repertoire diversity, * The phenotypic analysis of immune subpopulations, * The analysis of the global lymphopenia or subpopulations T, * The analyses by multiplex assay of a large panel of plasma cytokines and chemokines. | Biological | Lung cancer |
Primary outcome
Analyse the prognostic value of divpenia
Time frame: 3 month (lung cancer) 6 month (breast cancer)
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).
3 secondary outcomes
Analyse prognostic value of clinico-biological parameters (PS ECOG, LDH levels, - To establish that the divpenia factor is independent of clinical and biological prognostic factors (PS, LDH, metastasis localization, Hb, PMN, age, sex)
Time frame: 3 month (lung cancer) - 6 month (breast cancer)
Prognostic score NDL
Time frame: 3 month (lung cancer) - 6 month (breast cancer)
Characterization of other circulating markers
Time frame: 3 month (lung cancer) - 6 month (breast cancer)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2015.
- Results publication: PubMed 20537187Belbaraka R, Tredan O, Ray-Coquard I, Chvetzoff G, Bajard A, Perol D, Ismaili N, Ismaili M, Errihani H, Bachelot T, Rebattu P. Factors of interrupting chemotherapy in patients with Advanced Non-Small-Cell Lung Cancer. BMC Res Notes. 2010 Jun 10;3:164. doi: 10.1186/1756-0500-3-164.
- Results publication: PubMed 19549917Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, Tredan O, Verweij J, Biron P, Labidi I, Guastalla JP, Bachelot T, Perol D, Chabaud S, Hogendoorn PC, Cassier P, Dufresne A, Blay JY; European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009 Jul 1;69(13):5383-91. doi: 10.1158/0008-5472.CAN-08-3845. Epub 2009 Jun 23.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier TREDAN, MD principal investigator
Centre Leon Berard
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer and Lung Cancer, run by Centre Leon Berard at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Analyse the prognostic value of divpenia (time frame: 3 month (lung cancer) 6 month (breast cancer)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01306188, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2015.