Advanced Solid TumorPhase 1/2NCT03182803
CTLA-4 and PD-1 Antibodies Expressing Mesothelin-CAR-T Cells for Mesothelin Positive Advanced Solid Tumor
A Phase 1/2 study testing CTLA-4/PD-1 antibodies expressing mesoCAR-T in people with Advanced Solid Tumor, run by Shanghai Cell Therapy Research Institute at 1 site in China.
Trial summary
This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibodies (CTLA-4 and PD-1) and chimeric antigen receptor targeting mesothelin (mesoCAR-T) in adult patients with mesothelin positive, advanced… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- CTLA-4/PD-1 antibodies expressing mesoCAR-T
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 7 Jun 2017to 20 Apr 2019
- Phase
- Phase 1/2
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with relapsed or refractory advanced solid malignancies (diagnosed by histology or cytology detection).
- Progressive disease and no response after at least second-line therapy.
- Gender unlimited, age from 18 years to 80 years.
- Life expectancy ≥3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Adequate venous access for peripheral blood mononuclear cell (PBMC) apheresis, and no other contraindications.
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- Immunohistochemistry (IHC) score of mesothelin on tumor tissue ≥1+.
- Adequate bone marrow function, hepatic function and renal function (withhin 7 days before enrollment): white blood cell (WBC)≥3.0×10^9/L; platelet≥100×10^9/L; hemoglobin ≥90 g/L; lymphocyte ≥0.7×10^9/L; total bilirubin ≤2 times the upper limit of the normal value; alanine aminotransferase and aspartate transaminase(ALT and AST) ≤2.5 times the upper limit of the normal value; serum creatinine ≤1.5 times the upper limit of the normal value.
- There is no other treatments (chemotherapy, radiotherapy, etc.) within four weeks before enrollment.
- There is at least one measurable tumor lesion.
- Patients have adequate ability to understand, sign informed consents and take part in the clinical research voluntarily.
- Female patients in child bearing period must have evidence of negative pregnancy test, and agree to take effective contraceptive measures until 4 months after cells infusion.
Who cannot join
- Patients with two or more kinds of tumors.
- Patients with active viral or bacterial infection, and have failed to be controlled by anti-infective treatment.
- Patients with seropositive reponse of Human immunodeficiency virus (HIV) and syphilis, or fail to control the hepatitis B virus or hepatitis C virus infection.
- Patients with active rheumatic diseases, organ transplantation and other diseases affecting the immune system seriously.
- Patients with severe heart and lung dysfunction.
- Patients with severe chronic diseases of kidney, liver and other important organs.
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- Patients with any other illnesse that the investigators consider it will may affect the patient's treatments, follow-up or assessment, including any uncontrolled clinically significant neurological or psychiatric disorders, immunoregulatory diseases, metabolic diseases, infectious diseases and so on.
- Patients who take part in clinical trials of other drugs or biological therapy at present or within 30 days before enrollment.
- Patients who need long-term use of immunosuppressive drugs or patients who are undergoing treatment for autoimmune diseases.
- Patients who must use glucocorticoid for a long time.
- Women patients in gestation period or suckling period.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Ningbo No.5 Hospital (Ningbo Cancer Hospital)
Ningbo, Zhejiang, 315201
Bi Wang, 0086-0574-86689113, biwang0217@126.com
Jiangtao Wang
About this study
Official title: A Clinical Study of CTL-A4 and PD-1 Antibodies Expressing Mesothelin-CAR-T Cells for Patients With Mesothelin Positive Advanced Solid Tumors
This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibodies (CTLA-4 and PD-1) and chimeric antigen receptor targeting mesothelin (mesoCAR-T) in adult patients with mesothelin positive, advanced recurrent or refractory malignant solid tumors.
Read the detailed description
This study will be conducted using a phase I/II trial design to assess the efficacy and safety of the CTLA-4 and PD-1 antibodies expressing mesothelin-CAR-T (mesoCAR-T) for patients with mesothelin positive, advanced recurrent or refractory malignant solid tumors. MesoCAR-T can specificly and effectively kill the mesothelin positive cancer cells, CTLA-4 and PD-1 antibodies are secreted from the CAR-T cells could improve immunosuppression microenvironment, new CAR-T cells contain the advantages of CAR-T and immune checkpoint inhibitor, which is a promising therapeutic method for advanced solid tumors.
The new CAR-T therapy is applied to clinical practice as bellow. T cells are prepared from peripheral blood mononuclear cells by leukapheresis, then activated and engineered to CTLA-4 and PD-1 antibodies expressing and chimeric antigen receptor targeting mesothelin. Cells are proliferated in culture and returned to the patients by venous transfusion. A total of 40 patients may be enrolled in the study. The total duration of the study is expected to be approximately 24 months.
- Conditions
- Advanced Solid Tumor
- Being tested
- CTLA-4/PD-1 antibodies expressing mesoCAR-T
- Keywords
- mesothelin, CTLA-4, PD-1, chimeric antigen receptor T cells, solid tumor
- Medical subject headings
- Diabetes Mellitus, Insulin-Dependent, 12
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTLA-4/PD-1 antibodies expressing mesoCAR-TBiological
Every cycle, peripheral blood mononuclear cells (PBMC) are collected on day 0, CAR-T cells are cultured in a GMP standard workshop. Patients are given a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes before cells infusion. Then the patients will receive an i.v.gtt infusion of CTLA-4 and PD-1 antibodies expressing mesothelin-targeted CAR-T cells at (2-5) ×10^7 cells/kg from day 18 to day 19 (±2 days). 2 cycles are regarded as a treatment period.
| Study group | Role | What they receive |
|---|---|---|
| Anti-CTLA-4/PD-1 expressing meso-CAR-T | Experimental | This study have only one arm that is the CTLA-4/PD-1 antibodies expressing mesoCAR-T cells group. All patients with advanced solid tumors will take part in the screening, who matching all the conditions will be chosen for the treatment.New CAR-T cells are cultured from PBMC and returned to the patients by venous transfusion. Receives: Biological: CTLA-4/PD-1 antibodies expressing mesoCAR-T |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-related adverse events as assessed by CTCAE v4.0
Determine treatment-related adverse events of the immunotherapy with common toxicity criteria for adverse effects (CTCAE) version 4.0.
Measured: 2 years
Secondary outcomes (1)
The response evaluation of of the treatment for advanced solid tumors
The efficacy of the treatment is assessed according to the response evaluation criteria in solid tumor version 1.1 (RECIST1.1), which is defined as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2017
- Study start7 Jun 2017 (estimated)
- Primary completion20 Jan 2019 (estimated)
- Study completion20 Apr 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Cell Therapy Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Qijun Qian, Ph.D, Study chair, Shanghai Cell Therapy Research InstituteHuajun Jin, Ph.D, Study chair, Shanghai Cell Therapy Research InstituteZhiwei Zhang, Ph.D, Study director, Shanghai Cell Therapy Research InstituteYan Sun, Study director, Shanghai Cell Therapy Research InstituteJiangtao Wang, Principal investigator, Ningbo No.5 Hospital(Ningbo Cancer Hospital)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03182803
- Sponsor's protocol ID
- H2017-02-P01
- Status last verified
- Jun 2017
- First submitted
- 5 Jun 2017
- Last updated
- 9 Jun 2017
- Results posted
- No
- Data monitoring committee
- 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 9 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study of CTL-A4 and PD-1 Antibodies Expressing Mesothelin-CAR-T Cells for Patients With Mesothelin Positive Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03182803
- Acronym / sponsor ID
- H2017-02-P01
- Conditions
- Advanced Solid Tumor
- Keywords
- mesothelin, CTLA-4, PD-1, chimeric antigen receptor T cells, solid tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Shanghai Cell Therapy Research InstituteUniversity, hospital or other
- Study start
- 7 Jun 2017 (estimated)
- Primary completion
- 20 Jan 2019 (estimated)
- Study completion
- 20 Apr 2019 (estimated)
- First posted
- 9 Jun 2017 (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.
This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibodies (CTLA-4 and PD-1) and chimeric antigen receptor targeting mesothelin (mesoCAR-T) in adult patients with mesothelin positive, advanced recurrent or refractory malignant solid tumors.
Detailed description
This study will be conducted using a phase I/II trial design to assess the efficacy and safety of the CTLA-4 and PD-1 antibodies expressing mesothelin-CAR-T (mesoCAR-T) for patients with mesothelin positive, advanced recurrent or refractory malignant solid tumors. MesoCAR-T can specificly and effectively kill the mesothelin positive cancer cells, CTLA-4 and PD-1 antibodies are secreted from the CAR-T cells could improve immunosuppression microenvironment, new CAR-T cells contain the advantages of CAR-T and immune checkpoint inhibitor, which is a promising therapeutic method for advanced solid tumors.
The new CAR-T therapy is applied to clinical practice as bellow. T cells are prepared from peripheral blood mononuclear cells by leukapheresis, then activated and engineered to CTLA-4 and PD-1 antibodies expressing and chimeric antigen receptor targeting mesothelin. Cells are proliferated in culture and returned to the patients by venous transfusion. A total of 40 patients may be enrolled in the study. The total duration of the study is expected to be approximately 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-CTLA-4/PD-1 expressing meso-CAR-T | Experimental | Biological: CTLA-4/PD-1 antibodies expressing mesoCAR-TThis study have only one arm that is the CTLA-4/PD-1 antibodies expressing mesoCAR-T cells group. All patients with advanced solid tumors will take part in the screening, who matching all the conditions will be chosen for the treatment.New CAR-T cells are cultured from PBMC and returned to the patients by venous transfusion. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with relapsed or refractory advanced solid malignancies (diagnosed by histology or cytology detection).
- Progressive disease and no response after at least second-line therapy.
- Gender unlimited, age from 18 years to 80 years.
- Life expectancy ≥3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
Key exclusion criteria (11 listed)
- Patients with two or more kinds of tumors.
- Patients with active viral or bacterial infection, and have failed to be controlled by anti-infective treatment.
- Patients with seropositive reponse of Human immunodeficiency virus (HIV) and syphilis, or fail to control the hepatitis B virus or hepatitis C virus infection.
- Patients with active rheumatic diseases, organ transplantation and other diseases affecting the immune system seriously.
- Patients with severe heart and lung dysfunction.
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 |
|---|---|---|
| CTLA-4/PD-1 antibodies expressing mesoCAR-TEvery cycle, peripheral blood mononuclear cells (PBMC) are collected on day 0, CAR-T cells are cultured in a GMP standard workshop. Patients are given a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes before cells infusion. Then the patients will receive an i.v.gtt infusion of CTLA-4 and PD-1 antibodies expressing mesothelin-targeted CAR-T cells at (2-5) ×10^7 cells/kg from day 18 to day 19 (±2 days). 2 cycles are regarded as a treatment period. | Biological | Anti-CTLA-4/PD-1 expressing meso-CAR-T |
Primary outcome
Incidence of treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 2 years
Determine treatment-related adverse events of the immunotherapy with common toxicity criteria for adverse effects (CTCAE) version 4.0.
1 secondary outcome
The response evaluation of of the treatment for advanced solid tumors
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2017.
- 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.
Qijun Qian, Ph.D study chair
Shanghai Cell Therapy Research Institute
Huajun Jin, Ph.D study chair
Shanghai Cell Therapy Research Institute
Zhiwei Zhang, Ph.D study director
Shanghai Cell Therapy Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CTLA-4/PD-1 antibodies expressing mesoCAR-T in people with Advanced Solid Tumor, run by Shanghai Cell Therapy Research Institute 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 12 inclusion and 11 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 9 Jun 2017. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Zhiwei Zhang, Ph.D (0086-021-39595338 ext. 8008, zhangzw@shcell.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-related adverse events as assessed by CTCAE v4.0 (time frame: 2 years). 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 9 Jun 2017.