Solid Tumor, AdultPhase 1NCT03545815
Study of CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Mesothelin-directed CAR-T Cells in Patients With Mesothelin Positive Multiple Solid Tumors.
A Phase 1 study testing anti-mesothelin 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, we use the technique of CRISPR-Cas9 to knocked out the PD-1 and TCR of chimeric antigen receptor (CAR) T cells to effect the immuno-microenvironment around tumors. 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?
- anti-mesothelin 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
- 19 Mar 2018to 30 Dec 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.
- 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 0-3.
- 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):
- Absolute neutrophil count > 1,000/μl ii. Platelets >75,000/μl iii. Hemoglobin > 9 g/dL iv. Bilirubin < 2.0x the institutional normal upper limit unless secondary to bile duct obstruction by tumor v. Creatinine < 1.5x the institutional normal upper limit vi. Albumin ≥2 vii. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5x the institutional normal upper limit viii. Cardiac ejection fraction of >55% as measured by resting echocardiogram, with no significant pericardial effusion.
- Blood coagulation parameters: PT such that international normalized ratio (INR) is ≤ 1.5 and a PTT < 1.2 time 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
- Sarcomatoid MPM histology which is known in the literature to not express mesothelin; biphasic MPM is also excluded.
- This refers to non-commercially approved investigational drugs different than those used in this protocol.Participated in any other trial in which receipt of an investigational study drug occurred within 28 days prior to enrollment and anticipated treatment with another investigational product while on study.
- Anticipated need for systemic chemotherapy within 2 weeks before apheresis and infusion of CART-meso cells.
- Active invasive cancer other than the one of the three cancers in this study. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder and prostate cancer with PSA level < 1.0) are not excluded.CART-meso in mesothelin expressing cancers
- HIV, HCV, or HBV infections
- Active autoimmune disease (including but not limited to: systemic lupus erythromatosis, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) requiring immunosuppressive therapy within the past 4 weeks, with exception of thyroid replacement.
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- Patients with ongoing or active infection.
- Planned concurrent treatment with systemic high dose corticosteroids. Patients may be on a stable low dose of steroids (<10mg equivalent of prednisone) for chronic respiratory conditions.
- Patients requiring supplemental oxygen therapy.
- Prior therapy with gene modified cells.
- Previous experimental therapy with SS1 moiety, murine or chimeric antibodies (human and humanized antibodies are allowed).
- History of allergy to murine proteins
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
- Any clinically significant pericardial effusion; CHF (NY Heart Association Grade II-IV) or cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study. This determination will be made by a cardiologist.
- Any clinically significant pleural or peritoneal effusion that cannot be drained with standard approaches. An indwelling drainage device placed prior to enrollment is acceptable.
- Pregnant or breastfeeding women. Female study participants of reproductive potential must have a negative urine pregnancy test of enrollment. A serum pregnancy test will be performed within 2 weeks before infusion.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital
Beijing, 100853
Weidong Han, 86-10-13651392893, hanwdrsw@sina.com
About this study
Official title: Phase I Study to Evaluate Treatment of CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Chimeric Antigen Receptor (CAR) T Cells in Patients With Mesothelin Positive Multiple Solid Tumors.
Multiple solid tumors have positive targets of mesothelin expressed on the surfaces of the tumor cells, we use the technique of CRISPR-Cas9 to knocked out the PD-1 and TCR of chimeric antigen receptor (CAR) T cells to effect the immuno-microenvironment around tumors.
Read the detailed description
- To evaluate the feasibility and safety of CRISPR-Cas9 mediated PD-1 and TCR gene-knocked out chimeric antigen receptor (CAR) T cells in patients with mesothelin positive multiple solid tumors.
- To evaluate the duration of 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
- anti-mesothelin CAR-T cells
- Keywords
- mesothelin, CRISPR-Cas9, PD-1, TCR
- Medical subject headings
- Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-mesothelin CAR-T cellsBiological
Cells will be infused on day 0.
| Study group | Role | What they receive |
|---|---|---|
| anti-mesothelin CAR-T cells | 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.
Patients receive anti-mesothelin-CAR T cells on day 0. Receives: Biological: anti-mesothelin 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 signs/symptoms, toxicities and clinical
Measured: 24 weeks
Secondary outcomes (1)
clinical responses to anti-mesothelin cell infusions
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 posted4 Jun 2018
- Study start19 Mar 2018
- Primary completion30 Oct 2020 (estimated)
- Study completion30 Dec 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03545815
- Sponsor's protocol ID
- CHN-PLAGH-BT-028
- Status last verified
- Aug 2020
- First submitted
- 23 May 2018
- Last updated
- 10 Aug 2020
- 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 10 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study to Evaluate Treatment of CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Chimeric Antigen Receptor (CAR) T Cells in Patients With Mesothelin Positive Multiple Solid Tumors.
- ClinicalTrials.gov ID
- NCT03545815
- Acronym / sponsor ID
- CHN-PLAGH-BT-028
- Conditions
- Solid Tumor, Adult
- Keywords
- mesothelin, CRISPR-Cas9, PD-1, TCR
- 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
- 19 Mar 2018 (actual)
- Primary completion
- 30 Oct 2020 (estimated)
- Study completion
- 30 Dec 2020 (estimated)
- First posted
- 4 Jun 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, we use the technique of CRISPR-Cas9 to knocked out the PD-1 and TCR of chimeric antigen receptor (CAR) T cells to effect the immuno-microenvironment around tumors.
Detailed description
- To evaluate the feasibility and safety of CRISPR-Cas9 mediated PD-1 and TCR gene-knocked out chimeric antigen receptor (CAR) T cells in patients with mesothelin positive multiple solid tumors.
- To evaluate the duration of 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 |
|---|---|---|
| anti-mesothelin CAR-T cells | Experimental | Biological: anti-mesothelin 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. Patients receive anti-mesothelin-CAR T cells on day 0. |
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.
- 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 0-3.
Key exclusion criteria (16 listed)
- Sarcomatoid MPM histology which is known in the literature to not express mesothelin; biphasic MPM is also excluded.
- This refers to non-commercially approved investigational drugs different than those used in this protocol.Participated in any other trial in which receipt of an investigational study drug occurred within 28 days prior to enrollment and anticipated treatment with another investigational product while on study.
- Anticipated need for systemic chemotherapy within 2 weeks before apheresis and infusion of CART-meso cells.
- Active invasive cancer other than the one of the three cancers in this study. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder and prostate cancer with PSA level < 1.0) are not excluded.CART-meso in mesothelin expressing cancers
- HIV, HCV, or HBV infections
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 |
|---|---|---|
| anti-mesothelin CAR-T cellsCells will be infused on day 0. | Biological | anti-mesothelin CAR-T cells |
Primary outcome
study of related adverse events
Time frame: 24 weeks
Grade 3 signs/symptoms, toxicities and clinical
1 secondary outcome
clinical responses to anti-mesothelin cell infusions
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 10 Aug 2020.
- 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.
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 anti-mesothelin 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 16 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 10 Aug 2020. 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 Wweidong 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 10 Aug 2020.