Metastatic Renal Cell Carcinoma
Conditions
Brief summary
This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic advanced renal cancer. Blood samples will also be collected for research purposes.
Detailed description
This is a dose-escalation study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T cells from autologous origin. Patients are assigned to 1 of 3 treatment groups to determine the maximal tolerant dose. After the lower number of cycles are considered tolerant, an arm of the next higher number of cycles will be open to next patients. Biomarkers and immunological markers are collected and analyzed as well.
Interventions
BIOLOGICALPD-1 Knockout T Cells
PD-1 Knockout T Cells and PD-1 wild-type T Cells will be made by Cell Biotech Co., Ltd. 2x107/kg T cells will be used for test group and comparable group separately.
DRUGCyclophosphamide
Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion. Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit（IU）/Kg/day (if tolerant).
DRUGIL-2
Interleukin-2 (IL-2) will be given in the following 5 days after cell infusion, 720000 international unit（IU）/Kg/ day (if tolerant).
Sponsors
Peking University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Pathologically verified stage IV Renal cancer with measurable lesions (On CT: longest diameter of tumoral lesion \>=10 mm, shorted diameter of lymph node \>=15 mm; measurable lesions should not have been irradiated) * Progressed after all standard treatment * Performance score: 0-1 * Expected life span: \>= 6 months * Toxicities from prior treatment has resolved. Washout period is 4 weeks for chemotherapy, and 2 weeks for targeted therapy * Major organs function normally * Women at pregnant ages should be under contraception * Willing and able to provide informed consent
Exclusion criteria
* Pathology is mixed type * Emergent treatment of tumor emergency is needed * Poor vasculature * Coagulopathy, or ongoing thrombolytics and/or anticoagulation * Blood-borne infectious disease, e.g. hepatitis B * History of mandatory custody because of psychosis or other psychological disease inappropriate for treatment deemed by treating physician * With other immune diseases, or chronic use of immunosuppressants or steroids * Compliance cannot be expected * Other conditions requiring exclusion deemed by physician
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients | Dose Escalation - Approximately 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival - PFS | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months |
| Overall Survival - OS | The time from randomization to death from any cause, assessed up to 2 years |
| Peripheral blood circulating tumor DNA | 6 weeks |
| Response Rate:Response will be evaluated according to RECIST v1.1 | 90 days |
| Temporal Interferon-γ change in the peripheral blood | Baseline and 1 month and 3 months |
| Temporal Interleukin-6 change in the peripheral blood | Baseline and 1 month and 3 months |
| Temporal Interleukin-2 change in the peripheral blood | Baseline and 1 month and 3 months |
Outcome results
None listed