CAR-T Cell Immunotherapy for Advanced Lung Cancer
Study Details
Study Description
Brief Summary
The NSCLC patients who failed the standard treatments, with positive Programmed Death-Ligand 1 (PD-L1) expression, were enrolled into this trial. About 22 advanced NSCLC patients will be screened according to the criteria. The qualified patients will be recruited and sign the informed consent.Participants will be hospitalized and undergo clinical examinations.
Appropriate volume of peripheral blood will be draw (from 66 ml to 360 ml, depend on the body weight and blood routine test), using Ficoll method to centrifuge peripheral blood cell and collected T cells. PD-L1 CAR gene is cloned in a lenti-viral vector that was composed of T cell activation molecules (Cluster of Differentiation 137 (CD137/CD28) and Cluster of Differentiation 3(CD3) zeta intracellular domains) and PD-L1 single-chain variable fragment(scFv) derived from the variable regions of a PD-L1 monoclonal antibody.Then, investigators packaged pseudo-lentiviral particles in human embryonic kidney (293T) cells that will be used to transduce autologous T cells isolated from the patients. CAR positive T lymphocytes will be determined by FACS with florescence labeled goat anti-human F(ab')2. The plasmids, pseudo-lentiviral particles and transduced T cells will be subject to the stipulated tests by a third party.
Patients will receive leukodepletion chemotherapy (cyclophosphamide: 250mg/m2 × 3 days; fludarabine: 25mg/m2× 3 days). One day later, the chemotherapeutic effects would be assessed. PD-L1 CAR-T cells will be infused on day 0 with 10%, day 3 with 30% and day 7 with 60% (total number is (1-2)×10^6/kg). The patients will be observed closely for any adverse reactions and if happened, given supportive treatments.
The patients will be discharged on day 14 and will be followed up for two years according to the study scheme, i.e. once a month for the first three months; once every two months in the first year; since then, once a quarter in the second year. The persistence of PD-L1 CAR-T cells in the circulation will be monitored by fluorescent activated cell sorting (FACS) and polymerase chain reaction (PCR). If the patients undergo core needle biopsy, the infiltration of CAR positive cells in the tumor tissue will be evaluated by immunohistochemistry (IHC). The safety profile and anti-tumor efficacy of the CAR-T cells immunotherapy will be assessed during the whole process based on CTCAE v4.1 and RECIST v1.1.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
The morbidity and mortality of lung cancer ranks the first in all malignancies. Although targeted therapy such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) and activated lymphocyte kinase (ALK)-TKI can prolong non-small cell lung cancer (NSCLC) patients' survival, drug resistance almost occurs inevitably.
In recent years, PD-L1/PD-1 antibodies like Nivolumab and Pembrolizumab, show satisfactory therapeutic potential in the treatment of cancers like melanoma and lung cancer. Latest clinical investigations show that anti-PD-1 or PD-L1 antibody therapy can prolong patients' survival but actually only 20% of patients benefited from it.
Chimeric antigen receptor T-Cell (CAR-T) was genetically modified T lymphocytes by pseudo-lentiviral transduction to provide them with high binding affinity and specificity to the tumor antigen. That affinity was provided by CAR, independent from major histocompatibility complex (MHC).
CAR-T cell immunotherapy had shown tremendous success in the treatment of acute lymphocytic leukemia (ALL). Cluster of Differentiation (CD)-19 CAR-T cell treatment archived as high as 92% complete response rate for refractory and recurrent ALL. When the CAR-T cells targeting Her2/neu were given to the patients, mortality was observed from cardiopulmonary failure due to the weak expression of Her2/neu on the pulmonary epithelial cells. In contrast, Her2/neu antibody (trastuzumab) is widely applied safely in clinic to treat breast cancer patients. It strongly suggests that the CAR-T cells are more potent.
Thus investigators hypothesized that the CAR targeting tumor cell PD-L1 would significantly improve the efficacy of CAR-T cells and extend their application in the treatment of solid tumors, especially lung cancer. Investigators designed and cloned a PD-L1 CAR gene that targets the PD-L1 expressed on tumor cells. Given that PD-L1 CAR-T cells can effectively kill not only PD-L1 positive tumor cells in vivo but also immunosuppressive cells (like myeloid-derived suppressor cells (MDSCs)) inside tumors, they can remarkably improve immunosuppressive tumor microenvironment. Accordingly they can restore the function of tumor infiltrated T-lymphocytes(TILs) to achieve the synergistic effect of killing tumor cells that can greatly enhance the killing effects of PD-L1 CAR-T cells on tumor cells, even eliminate tumors.
The preclinical studies showed that PD-L1 CAR-T cells could be activated by and had significant killing effects on PD-L1 positive tumor cells in vitro. They inhibited tumor growth, while no obvious toxicity have been observed in mouse xenograft models. Investigators decide to explore the safety and efficacy of the new CAR-T cells in the phase I clinical study in the treatment of advanced NSCLC patients.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Single Arm CAR-T cells to treat advanced lung cancer. This study has only one arm. All participators will attend the screening and meet the set criteria for the clinical treatment. PD-L1 CAR-T cells are infused on day 0 with 10%, day 3 with 30% and day 7 with 60% , (1-2)×10^6/kg PD-L1 CAR-T cells total. |
Biological: CAR-T cells to treat advanced lung cancer
Drug: fludarabine. On days -4 through -2, fludarabine (25mg/m2) will be infused for 3 consecutive days; Drug: cyclophosphamide. On days -4 through -2, cyclophosphamide (250mg/m2) will be infused for 3 consecutive days.
Patients will receive the above chemotherapy for lymphocyte-depletion followed by PD-L1 CAR-T cells.
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Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events Associated With PD-L1 CAR-T Cell Treatment [From the date of CAR-T cell infusion through study completion, average 2 years]
Assessed by the treatment-emergent adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram. Treatment-emergent adverse events will be assessed and recorded according to CTCae v4.02. No statistical analysis was performed becuase the study was terminated after only 1 patient received treatment.
Secondary Outcome Measures
- Number of Participants Experiencing a Complete (CR) or Partial (PR) Tumor Response [Every three month through study completion, average 2 years]
Tumor response will be assessed according to RECIST V1.1. The overall response rate calculated by the numbers of PR or CR / all patients received treatment. The disease control rate calculated by the numbers of CR PR and stable disease / all patients received treatment.
Other Outcome Measures
- Numbers of Patients Received Surveillance of PD-L1 CAR-T Cells in Vivo [Day 7 after CAR-T cell infusion, and every 2 months up to 2 years]
Using flow cytometry to count of PD-L1 CAR-T cells, calculated the CAR-T cells existence by time after the infusion.
- Assessment of Count of the Functional B Cells in Peripheral Blood. [Baseline, day 7 and 30 after the CAR-T cell infusion]
Exploring the correlation of the immune functions of pre- and post-CAR-T cell treatments with the treatment safety and efficacy.
- Assessment of Count of the Functional T Cells in Peripheral Blood. [Baseline, day 7 and 30 after the CAR-T cell infusion]
Exploring the correlation of the immune functions of pre- and post-CAR-T cell treatments with the treatment safety and efficacy.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subjects were diagnosed with NSCLC by pathology and at clinical stages ⅢB/Ⅳ based on the 8th Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) Staging System or the disease has recurred or progressed after multi-mode therapy (radiotherapy, surgical excision or radical radiotherapy/chemotherapy to treat local advanced lesions ).
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Subjects whose recurrent or advanced NSCLC has progressed after standard treatments (operation, radiotherapy and targeting therapy, not including PD-1/PD-L1 checkpoint inhibition therapy) or who are reluctant to receive chemotherapy.
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Subjects should undertake core needle biopsy again to collect at least one fresh biopsy specimen and at least 10 non-stained sections before recruitment.
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TKI or chemotherapeutic should be discontinued at least 21 days before Day 0 of the clinical trial while radiotherapy of lung cancer at least 6 months before Day 0 of the clinical trial . Subjects should receive baseline imaging scan after the previous treatments are suspended.
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Lesions must be detected by CT or MRI according to RECIST 1.1 Criteria. Tumor imaging should be performed at least within 28 days before the beginning of the clinical study.
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Age>=18 years old and weight >=40kg.
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PD-L1 is positive by IHC in tissue biopsies of progressive lung cancer after standard treatments(>10%).Ventana PD-L1 (SP142) approved by FDA is used to detect PD-L1 expression level on participated patients' lung cancer sections.
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Life expectancy>=12 weeks
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Eastern Cooperative Oncology Group (ECOG) score≤ 2
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Blood pregnancy tests should be negative within 14 days before the woman of childbearing age starts treatment and agrees to take contraceptive methods with a failure rate of no more than 1% per year until the final follow-up.Contraceptive methods with a failure rate of no more than 1% per year include tubal ligation, vasectomy, hormonal contraceptives, intrauterine hormone release system and copper intrauterine device (IUDs).
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Hematology and liver and kidney functions should meet the following laboratory values. These laboratory tests should be completed in 7 days before the first therapeutic cell infusion.
Tests and Laboratory Values:
Hematology:
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White Blood Cell (WBC): >=3.5*10^9/L;
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Absolute Neutrophil Count (ANC): >=1.5*10^9/L;
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Hemoglobin (HGB): >=90g/L;
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Platelet (PLT): >=80*10^9/L;
Blood Coagulation Function:
PT、APTT、FIB、TT: within normal limits;
Liver Function:
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Aspartic Transaminase (AST): <2.5upper normal limits(ULN)(hepatic metastasis subjects with 0-1 ECOG score < 5ULN);
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Alanine Aminotransferase (ALT): <2.5ULN(hepatic metastasis subjects with 0-1 ECOG scorer < 5ULN);
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Total Bilirubin (TIBC): <1.5*ULN;
Kidney Function:
Serum Creatinine (CR): <1.0*ULN.
- Subjects are willing to participate in this study and agree to sign the Informed Consent.
Exclusion Criteria:
- Subjects who are receiving systematic steroid treatments 3 days before the first cell treatment.
Notice:
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Corticosteroids can be used to treat adverse event (AE) and serious adverse event (SAE) after the experimental cell treatment.
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Subjects who receive steroid replacement therapy everyday can be included in the clinical study. Prednisone therapy in a dose of 5-7.5mg/day is replacement therapy.
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Subjects who receive equivalent dose of hydrocortisone treatment as replacement therapy are also allowed into the clinical trial.
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Subjects who have received systematic cytotoxic chemotherapy, biological therapy or major operations in 3 weeks before the first dose of experimental cell therapy or subjects who have received lung radiation more than 30 gray (Gy) in 6 months before the first dose of experimental cell therapy.
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Subjects who have received previous cell treatments such as CAR-T and cytokine-induced killer (CIK) cells or anti-PD-1 or anti- PD-L1 antibody treatment.
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Subjects with confirmed Central Nervous System (CNS) metastasis and/or carcinomatous meningitis.
Notice:
Subjects who have received brain metastasis treatments are allowed in this study, in the case that subjects' conditions are stable (no CNS symptoms) and no radiographic evidence of new or extensive brain metastasis is found at least 4 weeks after the treatments (such as operation or RT). Subjects should suspend hormone treatment at least 3 days before the first dose of experimental cell treatment.
- Subjects with active autoimmune diseases who need systematic treatments (such as disease improving drugs, corticosteroids and immunosuppressive drugs) in the last 2 years.
Notice:
Replacement therapy (thyroxine, insulin or physiological corticosteroid replacement therapy to treat adrenal dysfunction or pituitary dysfunction) is not considered as systematic therapy. Subjects who need inhalation corticosteroid therapy can be included in this trial. Subjects with vitiligo or in long-term remission of pediatric asthma or allergic diseases can be included in this trial.
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Subjects with interstitial pneumonia or a history of pneumonia with oral or intravenous steroid treatments.
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Subjects whose lymphocytes are difficult to transduce (<20%) or can not proliferate over 5 times.
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Subjects who have received allotransplantation or solid organ transplantation.
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Subjects who have received or will receive live vaccines in 30 days before the first experimental cell treatment. Inactivated seasonal flu vaccination is allowed.
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Subjects with active infections who need intravenous systematic treatments.
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Subjects with a history of human immunodeficiency virus (HIV)(HIV 1/2 antibody positive)infection.
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Subjects with known active hepatitis B or hepatitis C. Subjects with HBsAg positive will be excluded. The definition of active hepatitis C is that hepatitis C antibody is positive while quantitative hepatitis C virus (HCV) RNA results exceed the lower detection limit.
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Subjects with a history of mental disorders or drug abuse that may influence treatment compliance.
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Women in pregnancy or lactation or are expected to be pregnant during the study (from the screening and to 60 days after the final experimental cell treatment) or men whose wives are in pregnancy.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- Sun Yat-sen University
- Guangzhou Yiyang Biological Technology Co., Ltd.
Investigators
- Principal Investigator: Li Zhang, M.D., Sun Yat-sen University
Study Documents (Full-Text)
More Information
Publications
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- Sholl LM, Aisner DL, Varella-Garcia M, Berry LD, Dias-Santagata D, Wistuba II, Chen H, Fujimoto J, Kugler K, Franklin WA, Iafrate AJ, Ladanyi M, Kris MG, Johnson BE, Bunn PA, Minna JD, Kwiatkowski DJ; LCMC Investigators. Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience. J Thorac Oncol. 2015 May;10(5):768-777. doi: 10.1097/JTO.0000000000000516.
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- CART-YY2017
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Treatment Arm |
---|---|
Arm/Group Description | CAR-T cells to treat advanced lung cancer. This study has only one arm. All participators will attend the screening and meet the set criteria for the clinical treatment. PD-L1 CAR-T cells are infused on day 0 with 10%, day 3 with 30% and day 7 with 60% , (1-2)×10^6/kg PD-L1 CAR-T cells total. CAR-T cells to treat advanced lung cancer: Drug: fludarabine. On days -4 through -2, fludarabine (25mg/m2) will be infused for 3 consecutive days; Drug: cyclophosphamide. On days -4 through -2, cyclophosphamide (250mg/m2) will be infused for 3 consecutive days. Patients will receive the above chemotherapy for lymphocyte-depletion followed by PD-L1 CAR-T cells. |
Period Title: Overall Study | |
STARTED | 1 |
COMPLETED | 1 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | Treatment Arm |
---|---|
Arm/Group Description | CAR-T cells to treat advanced lung cancer. This study has only one arm. All participators will attend the screening and meet the set criteria for the clinical treatment. PD-L1 CAR-T cells are infused on day 0 with 10%, day 3 with 30% and day 7 with 60% , (1-2)×10^6/kg PD-L1 CAR-T cells total. CAR-T cells to treat advanced lung cancer: Drug: fludarabine. On days -4 through -2, fludarabine (25mg/m2) will be infused for 3 consecutive days; Drug: cyclophosphamide. On days -4 through -2, cyclophosphamide (250mg/m2) will be infused for 3 consecutive days. Patients will receive the above chemotherapy for lymphocyte-depletion followed by PD-L1 CAR-T cells. |
Overall Participants | 1 |
Age, Customized (years) [Mean (Full Range) ] | |
age |
61
|
Sex: Female, Male (Count of Participants) | |
Female |
0
0%
|
Male |
1
100%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
1
100%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
0
0%
|
White |
0
0%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (participants) [Number] | |
China |
1
100%
|
Tumor Stage (Count of Participants) | |
Count of Participants [Participants] |
1
100%
|
EGFR mutation status (Count of Participants) | |
Count of Participants [Participants] |
1
100%
|
Outcome Measures
Title | Number of Participants With Treatment-Emergent Adverse Events Associated With PD-L1 CAR-T Cell Treatment |
---|---|
Description | Assessed by the treatment-emergent adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram. Treatment-emergent adverse events will be assessed and recorded according to CTCae v4.02. No statistical analysis was performed becuase the study was terminated after only 1 patient received treatment. |
Time Frame | From the date of CAR-T cell infusion through study completion, average 2 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment Arm |
---|---|
Arm/Group Description | CAR-T cells to treat advanced lung cancer. This study has only one arm. All participators will attend the screening and meet the set criteria for the clinical treatment. PD-L1 CAR-T cells are infused on day 0 with 10%, day 3 with 30% and day 7 with 60% , (1-2)×10^6/kg PD-L1 CAR-T cells total. CAR-T cells to treat advanced lung cancer: Drug: fludarabine. On days -4 through -2, fludarabine (25mg/m2) will be infused for 3 consecutive days; Drug: cyclophosphamide. On days -4 through -2, cyclophosphamide (250mg/m2) will be infused for 3 consecutive days. Patients will receive the above chemotherapy for lymphocyte-depletion followed by PD-L1 CAR-T cells. |
Measure Participants | 1 |
Count of Participants [Participants] |
1
100%
|
Title | Number of Participants Experiencing a Complete (CR) or Partial (PR) Tumor Response |
---|---|
Description | Tumor response will be assessed according to RECIST V1.1. The overall response rate calculated by the numbers of PR or CR / all patients received treatment. The disease control rate calculated by the numbers of CR PR and stable disease / all patients received treatment. |
Time Frame | Every three month through study completion, average 2 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment Arm |
---|---|
Arm/Group Description | CAR-T cells to treat advanced lung cancer. This study has only one arm. All participators will attend the screening and meet the set criteria for the clinical treatment. PD-L1 CAR-T cells are infused on day 0 with 10%, day 3 with 30% and day 7 with 60% , (1-2)×10^6/kg PD-L1 CAR-T cells total. CAR-T cells to treat advanced lung cancer: Drug: fludarabine. On days -4 through -2, fludarabine (25mg/m2) will be infused for 3 consecutive days; Drug: cyclophosphamide. On days -4 through -2, cyclophosphamide (250mg/m2) will be infused for 3 consecutive days. Patients will receive the above chemotherapy for lymphocyte-depletion followed by PD-L1 CAR-T cells. |
Measure Participants | 1 |
Count of Participants [Participants] |
1
100%
|
Title | Numbers of Patients Received Surveillance of PD-L1 CAR-T Cells in Vivo |
---|---|
Description | Using flow cytometry to count of PD-L1 CAR-T cells, calculated the CAR-T cells existence by time after the infusion. |
Time Frame | Day 7 after CAR-T cell infusion, and every 2 months up to 2 years |
Outcome Measure Data
Analysis Population Description |
---|
Only 1 patients received treatment and accepted the surveillance of PD-L1 CAR-T cells, and only one detection was performed at Day 7 time point |
Arm/Group Title | Treatment Arm |
---|---|
Arm/Group Description | CAR-T cells to treat advanced lung cancer. This study has only one arm. All participators will attend the screening and meet the set criteria for the clinical treatment. PD-L1 CAR-T cells are infused on day 0 with 10%, day 3 with 30% and day 7 with 60% , (1-2)×10^6/kg PD-L1 CAR-T cells total. CAR-T cells to treat advanced lung cancer: Drug: fludarabine. On days -4 through -2, fludarabine (25mg/m2) will be infused for 3 consecutive days; Drug: cyclophosphamide. On days -4 through -2, cyclophosphamide (250mg/m2) will be infused for 3 consecutive days. Patients will receive the above chemotherapy for lymphocyte-depletion followed by PD-L1 CAR-T cells. |
Measure Participants | 1 |
Count of Participants [Participants] |
1
100%
|
Title | Assessment of Count of the Functional B Cells in Peripheral Blood. |
---|---|
Description | Exploring the correlation of the immune functions of pre- and post-CAR-T cell treatments with the treatment safety and efficacy. |
Time Frame | Baseline, day 7 and 30 after the CAR-T cell infusion |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Assessment of Count of the Functional T Cells in Peripheral Blood. |
---|---|
Description | Exploring the correlation of the immune functions of pre- and post-CAR-T cell treatments with the treatment safety and efficacy. |
Time Frame | Baseline, day 7 and 30 after the CAR-T cell infusion |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Adverse Events
Time Frame | 24 months | |
---|---|---|
Adverse Event Reporting Description | Serious Cytokine Release Syndrome causes interstitial pneumonia disease. CTCAE grade 4, possibly drug related. Febrile without any courses and respiratory distress that deteriorated quickly into failure in 3 days.He was immediately transferred to the ICU where he received oxygen via nasal cannula and given intravenous infusions of tocilizumab and large doses of methylprednisolone. His symptoms were quickly improved and the pulmonary inflammation became dissipated gradually. | |
Arm/Group Title | Treatment Arm | |
Arm/Group Description | CAR-T cells to treat advanced lung cancer. This study has only one arm. All participators will attend the screening and meet the set criteria for the clinical treatment. PD-L1 CAR-T cells are infused on day 0 with 10%, day 3 with 30% and day 7 with 60% , (1-2)×10^6/kg PD-L1 CAR-T cells total. CAR-T cells to treat advanced lung cancer: Drug: fludarabine. On days -4 through -2, fludarabine (25mg/m2) will be infused for 3 consecutive days; Drug: cyclophosphamide. On days -4 through -2, cyclophosphamide (250mg/m2) will be infused for 3 consecutive days. Patients will receive the above chemotherapy for lymphocyte-depletion followed by PD-L1 CAR-T cells. | |
All Cause Mortality |
||
Treatment Arm | ||
Affected / at Risk (%) | # Events | |
Total | 1/1 (100%) | |
Serious Adverse Events |
||
Treatment Arm | ||
Affected / at Risk (%) | # Events | |
Total | 1/1 (100%) | |
Respiratory, thoracic and mediastinal disorders | ||
interstitial pneumonia disease | 1/1 (100%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Treatment Arm | ||
Affected / at Risk (%) | # Events | |
Total | 1/1 (100%) | |
Blood and lymphatic system disorders | ||
White blood cell counts increasing | 1/1 (100%) | 1 |
neutrophilic granulocytosis | 1/1 (100%) | 1 |
anemia | 1/1 (100%) | 1 |
thrombocytosis | 1/1 (100%) | 1 |
Eye disorders | ||
swelling of eye | 1/1 (100%) | 1 |
General disorders | ||
C-Reactive Protein | 1/1 (100%) | 1 |
Albumin decline | 1/1 (100%) | 1 |
Renal and urinary disorders | ||
Uric acid elevation | 1/1 (100%) | 1 |
proteinuria | 1/1 (100%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Serious Cytokine Release Syndrome causes interstitial pneumonia disease. | 1/1 (100%) | 1 |
upper respiratory tract infection | 1/1 (100%) | 1 |
hemoptysis | 1/1 (100%) | 1 |
Chest pain | 1/1 (100%) | 1 |
Skin and subcutaneous tissue disorders | ||
toothache | 1/1 (100%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr.Yuxiang Ma |
---|---|
Organization | Sun Yat-sen University Cancer Center |
Phone | 86 020 87343894 |
mayx@sysucc.org.cn |
- CART-YY2017