Malignant Solid Tumours
Conditions
Brief summary
The study is to determine the safety, feasibility and efficacy of allogeneic γδ T cell therapy in patients with solid tumors.
Detailed description
This is an open-label, single-center, phase 1/2 study to evaluate the safety, feasibility and efficacy of allogeneic γδ T cell therapy. In phase 1 period, a typical 3+3 dose-escalation design will be used to determine the optimal dose level based on the incidence of dose-limiting toxicity (DLT), which will be recommended as the fixed dose level in the following expansion period and phase 2. The initial infusion dose level will start from 2x10\^6/kg to 5x10\^7/kg in every 2-4 weeks. Combinations with chemotherapy, targeted therapy, radiotherapy, immune checkpoint inhibitors and other therapies are allowed in this study depending on the disease status of the enrolled patients.
Interventions
BIOLOGICALAllogeneic γδ T cells
Phase 1:Enrolled patents will be administered allogeneic γδ T cells from 2x10\^6/kg, 1 x10\^7/kg to 5x10\^7/kg every 2-4 weeks to determine the recommended dose level. Phase 2: Enrolled patents will be administered allogeneic γδ T cells at the recommended dose level to confirm the efficacy. Whether or not in combination with other therapies will be determined by research physicians according to the disease status of enrolled patients.
Sponsors
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Histological confirmation of malignant solid tumors, including patients received surgery, patients with initially diagnosed or pre-treated local advanced/metastatic malignancies, and patients with B-cell non-Hodgkin's lymphomas. 2. Patients should sign informed consent form voluntarily before the trail and comply with the requirements of this study. 3. Age from 18 to 75 years old, gender unlimited. 4. Eastern Cooperative Oncology Group (ECOG) Performance score≤2. 5. Patient with adequate bone marrow reserve (Haemoglobin≥80g/L, Absolute Neutrophil Count (ANC) ≥1×10\^6/L, Platelet≥75×10\^9/L or ≥50×10\^9/L for liver tumors), hepatic function (Aspartate Aminotransferase (AST) / Alanine Aminotransferase (ALT) ≤ 3.0x upper limit of normal or ≤ 5 x ULN for liver tumors or liver metastases, Total bilirubin ≤ 1.5 x ULN), renal function (Creatinine ≤ 1.5 x upper limit of normal (ULN)) and cardiac function (Left ventricular ejection fraction of ≥50% by ECHO). 6. Patient with life expectancy of at least 3 months. 7. Patient without bleeding and coagulation disorders. 8. Patient without obvious genetic diseases. 9. Toxicity from previous antitumor therapy ≤ grade 1 (according to CTCAE version 5.0) or to an acceptable level of inclusion/
Exclusion criteria
(other toxicities such as alopecia and vitiligo considered by the investigator to pose no safety risk to the subject). 10. Male and female patients of reproductive potential must agree to use birth control during the study and for at least 12 weeks post study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of severe adverse events | Baseline to Day 100 | Safety of the γδ T cell infusion will be based on the risk of treatment-related severe adverse events as identified in the National Cancer Common Terminology Criteria for Adverse Events (CTCAE) version 5. |
| Incidence of dose-limiting toxicity (DLT) | Baseline to Day 30 | The dose escalation strategy will follow the Food and Drug Administration Guideline for design of early phase clinical trials of cellular therapy products. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | Baseline to 2years | The duration of objective response in patients will be recorded until 2years after the start of 1st cycle of treatment |
| Overall Survival | Baseline to 2years | Observation for overall survival l (OS) will be recorded until 2years after the start of 1st cycle of treatment. |
| Progress Free Survival | Baseline to 2years | Observation for progression-free survival (PFS) will be recorded until 2years after the start of 1st cycle of treatment |
| Intervention Treatment-related adverse events(AEs) | Baseline to 12 months | Incidence, nature ,and severity of adverse events will be graded according to the NCI CTCAEv5.0. |
| Objective Response Rate | Baseline to 2years | Objective clinical response will be assessed by investigators every 2 circles during the treatments and every 2 months after treatment until 2 years after the start of 1st cycle of treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory research | Baseline to 12 months | γδ T cells in peripheral blood after infusion will be analysed by TCR or flow cytometry. |
Countries
China
Contacts
Primary ContactWeidong Han, M.D
Outcome results
None listed