This study is a single arm, open label, dose exploring clinical study to evaluate the safety, efficacy, metabolic kinetics and pharmacodynamics of CT1182 cells in patients with relapsed / refractory B-cell non Hodgkin lymphoma (r/r B-NHL).
The MTD target toxicity probability of this study is set at 30%. Four dose levels are tentatively determined for dose increment: 1.2 × 10 \^ 8, 3.0 × 10 \^ 8, 6.0 × 10 \^ 8, 1.2 × 10 \^ 8 Tu CT1182. It is planned to enroll 3-24 participants. The number of cases in each dose group shall be subject to the actual situation. The dose increment method of Boin design was used for dose increment. If the exploration dose is not confirmed as the possible maximum tolerated dose (MTD), the investigator and the sponsor can jointly discuss whether to increase to a higher dose or decrease to a lower dose to explore the possible MTD. The observation period of DLT was 28 days after the first infusion. If no obvious expansion of CD19/CD20 car-t cells is detected within 28 days after infusion, the researchers judged that the treatment may be ineffective due to the low infusion dose, or the study participants may withdraw from the treatment early due to disease progression and other reasons, and it is still necessary to continue to observe the safety of the study participants until the 28 day observation period is completed. If DLT is not observed, and the investigator evaluates that the dose of this dose group is too low to benefit the patients, the dose group can no longer continue to be included in the study participants, but can continue to climb the dose of the next dose group. The main purpose of this study was to explore the safety and tolerability of CT1182 among the study participants. The primary endpoint was to evaluate the frequency, type and severity of adverse events after CT1182 infusion, as well as DLT and MTD.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
CT1182 injection is an in vivo car-t product (CT1182) independently developed by carsgen company based on carvivo ™ platform, which simultaneously targets CD19 and CD20. Carvivo ™ platform uses redirected lentiviral vector technology to directly target and transduce T cells and generate functional car-t cells in vivo after intravenous infusion of lentivirus to achieve specific targeted killing of tumor cells. The CT1182 product adopts an optimized mutant engineered vesicular stomatitis virus (VSV) envelope, which makes the lentivirus lose its pan tropism. At the same time, it loads redirected CD3 targeting molecules on the virus surface to achieve specific transduction of T cells.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGFrequency, type and severity of AES
To evaluate the severity and incidence of treatment-related adverse events (TARE) and adverse events of special concern (AESI) after CT1182 infusion
Time frame: Within 24 months after CT1182 infusion
The number and severity of dose-limiting toxicity (DLT)events
DLT was collected to explore the maximum tolerated dose (MTD) and / or dose range of CT1182
Time frame: Within 28 days after CT1182 infusion
Investigator assessed objective response rate (ORR)
Time frame: The evaluation was performed within 24 months after CT1182 infusion, such as 4 weeks, 8 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months, 24 months, after CT1182 infusion
Investigator assessed complete response rate (CRR)
Time frame: The evaluation was performed within 24 months after CT1182 infusion, such as 4 weeks, 8 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months, 24 months, after CT1182 infusion
Investigator assessed duration of remission (DOR)
Time frame: The evaluation was performed within 24 months after CT1182 infusion, such as 4 weeks, 8 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months, 24 months, after CT1182 infusion
Investigator assessed time to remission (TTR)
Time frame: The evaluation was performed within 24 months after CT1182 infusion, such as 4 weeks, 8 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months, 24 months, after CT1182 infusion
Investigator assessed time to complete remission (TTCR)
Time frame: The evaluation was performed within 24 months after CT1182 infusion, such as 4 weeks, 8 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months, 24 months, after CT1182 infusion
Investigator assessed progression free survival (PFS)
Time frame: The evaluation was performed within 24 months after CT1182 infusion, such as 4 weeks, 8 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months, 24 months, after CT1182 infusion
Overall survival (OS)
Time frame: The evaluation was performed within 24 months after CT1182 infusion, such as 4 weeks, 8 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months, 24 months, after CT1182 infusion
Levels of free lentiviral vectors in peripheral blood
Time frame: Before administration, 6 hours after administration and 24, 48 and 96 hours after administration
The level of CD19/CD20 CAR gene copy number
Time frame: Day 0 before CT1182 infusion, Day 1, Day 2, Day 4, Day 6,Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 28, Week 8,Week 12, Month 6, Month 9 and Month 12 after CT1182 infusion
Duration of CD19/CD20 CAR gene copy number
Time frame: Day 0 before CT1182 infusion, Day 1, Day 2, Day 4, Day 6,Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 28, Week 8,Week 12, Month 6, Month 9 and Month 12 after CT1182 infusion
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