Solid Tumor, AdultPhase 1NCT03747965
Study of PD-1 Gene-knocked Out Mesothelin-directed CAR-T Cells With the Conditioning of PC in Mesothelin Positive Multiple Solid Tumors
A Phase 1 study testing Mesothelin-directed CAR-T cells in people with Solid Tumor, Adult, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
Multiple solid tumors have positive targets of mesothelin expressed on the surfaces of the tumor cells, the investigators use the technique of CRISPR-Cas9 to knocked out the PD-1 of the chimeric antigen receptor (CAR) T cells with the combination of Pretreatment by Paclitaxel and Cyclophosphamideto to effect the… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Solid Tumor, Adult
- What is being tested?
- Mesothelin-directed CAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- Nov 2018to May 2020
- Phase
- Phase 1
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed with mesothelin positive multiple solid tumors, especially in Pancreatic cancer, cholangiocarcinoma cancer and ovarian cancer .
- Failure of at least one prior standard of care chemotherapy for advanced stage disease.
- Subjects must have measureable disease as defined by RECIST 1.1 criteria or modified RECIST criteria.
- Patients > 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy > 12 weeks.
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- Satisfactory organ and bone marrow function as defined by the following (of note, the minimal blood counts should be in the absence of transfusion or cytokine support):
- i.Absolute neutrophil count > 1,000/μl ii.Platelets >75,000/μl iii.Hemoglobin > 9 g/dL iv.Bilirubin < 2 times of the institutional normal upper limit unless secondary to bile duct obstruction by tumor v.Creatinine < 1.5 times of the institutional normal upper limit vi.Albumin ≥2 vii.Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 times of the institutional normal upper limit viii.Cardiac ejection fraction of >45% as measured by resting echocardiogram, with no significant pericardial effusion ix.Normal lung function
- Blood coagulation parameters: PT such that international normalized ratio (INR) is ≤ 1.5 and a PTT < 1.2 times of the upper limit of normal unless the patient is therapeutically anti-coagulated for history of cancer-related thrombosis and has stable coagulation parameters.
- Ability to understand and the willingness to provide written informed consent.
- Male and Female subjects of reproductive potential agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device, abstinence) and abstain from other methods of conception during the study and for 6 months following the study cell infusion or proof of sterility.
Who cannot join
- Patients with moderate or higher hydrothorax and abdominal effusion, which are difficult to control by conventional treatment and require continuous catheter drainage;
- Either of the following virological tests is positive: HIV;HCV.HBsAg;Positive HBV DNA copy number was detected simultaneously (quantitative detection was 5 x 10^2 copies/ml).RPR or TPPA positive;
- Other malignant tumors, with the exception of basal cell carcinoma of the skin, superficial cervical cancer, bladder cancer, and prostate cancer(PSA value < 1.0) that do not require further treatment;
- Accompanied by central metastasis;
- Severe, uncontrollable comorbidities that may affect program compliance or interpretation of interference results, or any serious medical conditions that may affect the safety of the subject (such as uncontrollable heart disease, hypertension, active virus, bacterial infection or uncontrollable systemic fungal infection);
- Active autoimmune diseases (including but not limited to systemic lupus erythematosus, sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) need to be treated with immunosuppressive therapy within 4 weeks before enrollment, with the exception of thyroid hormone replacement therapy;
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- Subjects are receiving immunosuppressive, glucocorticoid (systemic or local) therapy (dose >10mg/ day prednisone or other equivalent hormones), and continue to use it within 2 weeks before enrollment;
- With the history of organ transplantation;
- Subjects who were given the last treatment less than 4 weeks before the initial treatment or participated in other relevant clinical study subjects at the same time;
- With the history of gene therapy;
- During the period of first study, live vaccines were administered within 4 weeks before PBMC collection;
- People who have a history of psychotropic drug abuse and are unable to get rid of it or have a history of mental disorders;
- Life-threatening allergic, hypersensitive, or intolerant reactions to GC008t preparations or their excipients (including DMSO) are known;
- Hemorrhagic and thrombotic tendencies:3 months prior to study drug treatment for the first time there have been significant clinical significance of bleeding symptoms or have a definite bleeding tendency, such as gastrointestinal bleeding, bleeding ulcers, coagulant function abnormality (PT > 16 s, APTT, TT > > 43 s 21 s, FIB < 2 g/L), there is tendency of inherited or acquired bleeding and thrombosis (such as hemophilia, blood coagulation dysfunction, thrombocytopenia, the splenic function, etc.), were treated with thrombolysis and anticoagulation, 6 months prior to study drug treatment for the first time move/enous thromboembolism events,Such as cerebral vascular diseases (including cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
- Other severe, acute or chronic medical or mental illnesses that may increase the risk of participating in the study or may interfere with the interpretation of the results, according to the researchers.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
Weidong Han, Dr, 86-10-13651392893, hanwdrsw@sina.com
About this study
Official title: Phase I Study of CRISPR-Cas9 Mediated PD-1 Gene-knocked Out Mesothelin-directed CAR-T Cells With the Conditioning Regimen of Paclitaxel and Cyclophosphamide in Mesothelin Positive Multiple Solid Tumors
Multiple solid tumors have positive targets of mesothelin expressed on the surfaces of the tumor cells, the investigators use the technique of CRISPR-Cas9 to knocked out the PD-1 of the chimeric antigen receptor (CAR) T cells with the combination of Pretreatment by Paclitaxel and Cyclophosphamideto to effect the immuno-microenvironment around tumors.
Read the detailed description
- To evaluate the feasibility and safety of CRISPR-Cas9 mediated PD-1 gene-knocked out chimeric antigen receptor (CAR) T cells in patients with mesothelin positive multiple solid tumors.
- To evaluate the duration and in vivo persistence of transferred CAR-T cells.
- To observe and measure anti-tumor responses for patients with detectable mesothelin positive tumor lesions.
- Conditions
- Solid Tumor, Adult
- Being tested
- Mesothelin-directed CAR-T cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesothelin-directed CAR-T cellsBiological
Cells will be infused one day after the completion of conditioning regimen of paclitaxel and cyclophosphamide
| Study group | Role | What they receive |
|---|---|---|
| Mesothelin-directed CAR-T cells infusion | Experimental | Patients receive mesothelin-directed CAR-T cells infusion with dose escalation will occur using a standard "3+3" dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Receives: Biological: Mesothelin-directed CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study of related adverse events
Grade 3 or severer signs/symptoms, toxicities and clinical
Measured: 24 weeks
Secondary outcomes (1)
Clinical responses of mesothelin-directed CAR T cells infusion
Disease control rate(DCR)
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2018
- Study startNov 2018 (estimated)
- Primary completionNov 2019 (estimated)
- Study completionMay 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor, AdultStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
- Investigators
- Weidong Han, Dr, Study director, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03747965
- Sponsor's protocol ID
- S2017-074-01
- Status last verified
- Nov 2018
- First submitted
- 19 Nov 2018
- Last updated
- 20 Nov 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of CRISPR-Cas9 Mediated PD-1 Gene-knocked Out Mesothelin-directed CAR-T Cells With the Conditioning Regimen of Paclitaxel and Cyclophosphamide in Mesothelin Positive Multiple Solid Tumors
- ClinicalTrials.gov ID
- NCT03747965
- Acronym / sponsor ID
- S2017-074-01
- Conditions
- Solid Tumor, Adult
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- Nov 2018 (estimated)
- Primary completion
- Nov 2019 (estimated)
- Study completion
- May 2020 (estimated)
- First posted
- 20 Nov 2018 (actual)
- 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.
Multiple solid tumors have positive targets of mesothelin expressed on the surfaces of the tumor cells, the investigators use the technique of CRISPR-Cas9 to knocked out the PD-1 of the chimeric antigen receptor (CAR) T cells with the combination of Pretreatment by Paclitaxel and Cyclophosphamideto to effect the immuno-microenvironment around tumors.
Detailed description
- To evaluate the feasibility and safety of CRISPR-Cas9 mediated PD-1 gene-knocked out chimeric antigen receptor (CAR) T cells in patients with mesothelin positive multiple solid tumors.
- To evaluate the duration and in vivo persistence of transferred CAR-T cells.
- To observe and measure anti-tumor responses for patients with detectable mesothelin positive tumor lesions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mesothelin-directed CAR-T cells infusion | Experimental | Biological: Mesothelin-directed CAR-T cellsPatients receive mesothelin-directed CAR-T cells infusion with dose escalation will occur using a standard "3+3" dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically confirmed with mesothelin positive multiple solid tumors, especially in Pancreatic cancer, cholangiocarcinoma cancer and ovarian cancer .
- Failure of at least one prior standard of care chemotherapy for advanced stage disease.
- Subjects must have measureable disease as defined by RECIST 1.1 criteria or modified RECIST criteria.
- Patients > 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (15 listed)
- Patients with moderate or higher hydrothorax and abdominal effusion, which are difficult to control by conventional treatment and require continuous catheter drainage;
- Either of the following virological tests is positive: HIV;HCV.HBsAg;Positive HBV DNA copy number was detected simultaneously (quantitative detection was 5 x 10^2 copies/ml).RPR or TPPA positive;
- Other malignant tumors, with the exception of basal cell carcinoma of the skin, superficial cervical cancer, bladder cancer, and prostate cancer(PSA value < 1.0) that do not require further treatment;
- Accompanied by central metastasis;
- Severe, uncontrollable comorbidities that may affect program compliance or interpretation of interference results, or any serious medical conditions that may affect the safety of the subject (such as uncontrollable heart disease, hypertension, active virus, bacterial infection or uncontrollable systemic fungal infection);
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 |
|---|---|---|
| Mesothelin-directed CAR-T cellsCells will be infused one day after the completion of conditioning regimen of paclitaxel and cyclophosphamide | Biological | Mesothelin-directed CAR-T cells infusion |
Primary outcome
Study of related adverse events
Time frame: 24 weeks
Grade 3 or severer signs/symptoms, toxicities and clinical
1 secondary outcome
Clinical responses of mesothelin-directed CAR T cells infusion
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2018.
- Individual participant dataSharing planned: No
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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.
Weidong Han, Dr study director
Chinese PLA General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mesothelin-directed CAR-T cells in people with Solid Tumor, Adult, run by Chinese PLA General Hospital at 1 site in China.
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 11 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 20 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Weidong Han, Dr (86-10-13651392893, hanwdrsw@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Study of related adverse events (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Nov 2018; AzTrials last refreshed its copy on 7 Nov 2026.