Description:
A Chimeric Switch Receptor, which was constructed by fusing the PD1 extracellular ligand
binding domain to the CD28 intracellular costimulatory domain, was designed to target PD-L 1
positive tumors . In this single-arm, open-label, one center, dose escalation clinical study,
the main purpose is to determine the safety and efficacy of infusion of autologous Chimeric
Switch Receptor modified T cells (CSR T) in adult patients with PD-L1 positive, recurrent or
metastatic malignant tumors.
Title
- Brief Title: Chimeric Switch Receptor Modified T Cells for Patients With PD-L1+ Recurrent or Metastatic Malignant Tumors
- Official Title: A Safety and Efficacy Study of Chimeric Switch Receptor Modified T Cells in Patients With Recurrent or Metastatic Malignant Tumors
Clinical Trial IDs
- ORG STUDY ID:
K16-3
- NCT ID:
NCT02930967
Conditions
- Recurrent PD-L1+ Malignant Tumors
- Metastatic PD-L1+ Malignant Tumors
Interventions
Drug | Synonyms | Arms |
---|
autologous CSR T | | CSR T cells |
Purpose
A Chimeric Switch Receptor, which was constructed by fusing the PD1 extracellular ligand
binding domain to the CD28 intracellular costimulatory domain, was designed to target PD-L 1
positive tumors . In this single-arm, open-label, one center, dose escalation clinical study,
the main purpose is to determine the safety and efficacy of infusion of autologous Chimeric
Switch Receptor modified T cells (CSR T) in adult patients with PD-L1 positive, recurrent or
metastatic malignant tumors.
Trial Arms
Name | Type | Description | Interventions |
---|
CSR T cells | Experimental | A dose escalation clinical study aimed to assess the safety and efficacy of CSR T cells in patients with PD-L1 positive tumors.
CSR T dosage ranging from: 5×10^4 /kg to 1×10^7 /kg will be tested. | |
Eligibility Criteria
Inclusion Criteria:
1. Patients with PD-L1 positive, recurrent or metastatic malignant tumors , including but
not limited to pancreatic cancer, renal cancer, colorectal cancer, lymphoma, breast
cancer and lung cancer;
2. measurable tumors by RECIST1.1 standard;
3. patients are 18 to 70 years old;
4. life expectancy > 3months;
5. KPS ≥70;
6. satisfactory major organ functions: adequate heart function with LVEF≥50%; no obvious
abnormities in ECG; pulse oximetry ≥ 90%; cockcroft-gault creatinine clearance≥40
ml/min; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3ULN;
Bilirubin ≤2.0 mg/dl ;
7. Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L;
8. women of reproductive potential must have a negative pregnancy test. Male and female
of reproductive potential must agree to use birth control during the study and one
year post study.
Exclusion Criteria:
1. patients with a prior history of autoimmune disease or other diseases who need
long-term use of systemic hormone drug or immunosuppressive therapy
2. active infection.
3. HIV positive.
4. active hepatitis B virus infection or hepatitis C virus infection.
5. currently enrolled in other study.
6. patients, in the opinion of investigators, may not be eligible or are not able to
comply with the study.
7. patients with allergic disease, or are allergic to T cell products or other biological
agents used in the study.
8. patients whose tumors have metastasized to bone, or have clinical signs of bone
metastasis, such as bone and joint pain.
9. patients with brain metastasis, or have clinical signs of brain metastasis, such as
loss of self-consciousness.
Maximum Eligible Age: | 70 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Safety as assessed by incidents of treatment related adverse events as assessed by CTCAE V4.0. |
Time Frame: | 2 years |
Safety Issue: | |
Description: | safety of infusion of autologous CSR T cells with cyclophosphamide as lymphodepleting chemotherapy |
Secondary Outcome Measures
Measure: | treatment response rate of CSR T cell infusion |
Time Frame: | 4 weeks |
Safety Issue: | |
Description: | defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). |
Measure: | overall survival rate |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | progression-free survival |
Time Frame: | 6 months |
Safety Issue: | |
Description: | |
Measure: | proliferation of CSR T cells in patients |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Persistence of CSR T cells in patients |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Unknown status |
Lead Sponsor: | China Meitan General Hospital |
Last Updated
October 12, 2016