- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03179007
CTLA-4 and PD-1 Antibodies Expressing MUC1-CAR-T Cells for MUC1 Positive Advanced Solid Tumor
A Clinical Study of CTLA-4 and PD-1 Antibodies Expressing MUC1-CAR-T Cells for Patients With MUC1 Positive Advanced Solid Tumors
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study will be conducted using a phase I/II trial design to assess the safety and efficacy of the CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T for patients with MUC1 positive, advanced recurrent or refractory malignant solid tumors. MUC1-CAR-T can specificly and effectively kill the MUC1 positive cancer cells, CTLA4 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 (PBMC) by leukapheresis, and then activated and engineered to express CTLA-4 and PD-1 antibodies and chimeric antigen receptor targeting MUC1. 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 Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Zhiwei Zhang, Ph.D
- Phone Number: 0086-021-39595338
- Email: zhangzw@shcell.com
Study Locations
-
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Zhejiang
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Ningbo, Zhejiang, China, 315201
- Recruiting
- Ningbo No.5 Hospital (Ningbo Cancer Hospital)
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
- Immunohistochemistry (IHC) score of MUC1 on tumor tissue ≥1+.
- Adequate hepatic function, renal function and bone marrow 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.
Exclusion Criteria:
- 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.
- Patients with any other serious 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 of autoimmune diseases.
- Patients who need long-term use of glucocorticoid.
- Women patients in gestation period or suckling period.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Anti-CTLA-4/PD-1 expressing MUC1-CAR-T
This study have only one arm that is anti-CTLA-4/PD-1 expressing MUC1-CAR-T group.
All patients with advanced solid tumor will take part in the screening, who matching all the conditions will be chosen for the treatment using CTLA-4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells.
New CAR-T cells are cultured from PBMC and returned to the patients by venous transfusion.
|
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 MUC1 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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of infusion of autologous CTLA-4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells
Time Frame: 2 years
|
Determine the toxicity profile of CTLA4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The efficacy of the treatment using CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T cells for advanced solid tumors
Time Frame: 2 years
|
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).
|
2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival
Time Frame: 2 years
|
Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause.
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2 years
|
Overall survival
Time Frame: 2 years
|
Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.
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2 years
|
Change of life quality
Time Frame: 2 years
|
Life quality is assessed before and after the treatment.
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2 years
|
Proliferation and persistence of MUC1 specific CAR-T cells in peripheral blood of the patients after treatment
Time Frame: 6 months
|
CAR-T proportion in peripheral blood of the patients is detected by flow cytometry assay to study the proliferation and persistence of MUC1 specific CAR-T cells.
|
6 months
|
CTLA-4 and PD-1 antibodies level in peripheral blood of the patients after treatment
Time Frame: 6 months
|
CTLA-4 and PD-1 antibodies level are detected by ELISA assay to asess the expressing level of CTLA4 and PD-1 antibodies from CAR-T cells.
|
6 months
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- H2017-04-P01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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