Malignant Tumor of Urinary System (Disorder) Clinical Trial
Official title:
A Phase I/Ⅱ a Clinical Study to Evaluate the Safety, Tolerance, Pharmacokinetics and Efficacy of Sc610 Cell Injection in the Treatment of Advanced Urinary System Tumors
This is an phase I/IIa, open-lable, single-arm, single-dose escalation and multiple-dose extention clinical study of cell therapy designed to observe and evaluate the tolerance, the pharmacokinetic characteristics, the safety and the efficacy of Sc610 cell injection in the treatment of advanced tumor of urinary system.
This study consists of two phases: the first phase will be the dose exploration phase (Phase I), followed by the dose extension phase (Phase II). In phase I, 3 subjects are enrolled for 1st treatment group, starting with single dose of Sc610 cell injection of 5.0x10^8. If there is no dose limiting toxicity (DLT) observed, 3 subjects are enrolled into treatment groups successively in sequential order of: 1) group 2: Single dose of Sc610 1.5x10^9; 2) group 3: Single dose of Sc610 5x10^9; and 3) gorup 4: Single dose of Sc610 1.5x10^10. Starting from the completion of Sc610 reinfusion for first subject of the 1st dose group, the subject will be observed for no less than one week. If no serious toxic and adverse events occurrs, Sc610 reinfusion for the second and third subjects will be performed. If no DLT occurrs by the 14th days after completion of reinfusion for the 3rd subject, The study will proceed to the next treatment group. If DLT is observed in 1/3 of enrolled subjects, another 3 subjects will be enrolled. In any of the dose groups, if ≤1/6 subjects have DLT, subject enrollment for the next treatment group will start. If DLT occurs in ≥2/6 of subjects, the number of subjects in the previous dose group shall be reviewed. If there were only 3 subjects, 3 more subjects will be enrolled. If DLT occurs in ≤1/6 subjects, the dose will be defined as the maximum tolerable dose (MTD), and the dose escalation phase of the study will be completed. If DLT occurs in ≥2/6 subjects in the first dose group, a dose reduction exploration will be performed or the study will be terminated upon decision made by the Safety Committee. In phase II, If no dose limiting toxicity event occurred upon the completion of treatment in each of the 4 groups. Researcher will decide to select 2-4 dose groups for dose extension study and will enroll 5-8 subjects for each group. Certain subjects have the option to receive multiple rounds of Sc610 treatment: 1) Subjects with unconfirmed disease progression (non iCPD, i.e. iUPD, iSD, iPR) as assessed by the response to the cell treatment by medical imaging of last round of treatment can enter multiple rounds of treatment. Subjects with complete remission (iCR) will be allowed to receive one consolidation treatment；Subjects whose response to the cell treatment as assessed by medical imaging are disease progression (iCPD), and the investigator judge that the subjects would be unable to benefit from the treatment of this study, and need to receive a new treatment or change the treatment method, will fall off/withdraw from the trial. 2) Before entering the next round of treatment each time, the percentage of PD-1+T cells in total T cells need to be assayed first, and peripheral blood monocytes apheresis can be performed if the detection result is≥18% (PBMCs≥3 x10^9). The procedures of preparation, reinfusion, and follow-ups after reinfusion of Sc610 cell injection are the identical as before. 3) If toxic reaction related to Sc610 greater than grade 3 cells is observed in previous dose (round) of treatment, the dose of next round will be reduced; If adverse events above grade 3 still occur after dose reduction, the investigator will make a comprehensive judgment on whether to terminate the study of this subject. 4) Multiple round treatment is a treatment cycle every 12 weeks. After treatment, follow up until the disease progresses, or start a new anti-tumor treatment, or fall off, or withdraw from the trial. ;