This study is a single arm, open label, dose exploring clinical trial to evaluate the safety, efficacy, cellular metabolic dynamics, and pharmacodynamics of ct1190b cells in relapsed / refractory B-cell acute lymphoblastic leukemia.
The study was divided into dose escalation phase and dose expansion phase. It is planned to enroll 18-36 study participants. The participants were divided into two treatment groups. Group A was adult participants ≥ 18 years old who received ct1190b treatment. The dose escalation was tentatively determined at three dose levels: dl1:3.0 × 10\^8, dl2:4.5 × 10\^8, dl3:6.0 × 10\^8 car-t cells. , Group B consisted of 12-17-year-old adolescents and children. The dose escalation was tentatively defined as two dose levels. Dl1:3.0 × 10\^6 /kg car-t cells, the maximum total number of infused cells was not more than 1.5 × 10\^8 car-t cells, dl2:6.0 × 10\^6 /kg car-t cells, the maximum total number of infused cells was not more than 3.0 × 10\^8 car-t cells. The dose escalation of the two groups followed the "i3+3" design. It was planned to enroll 18-36 study participants. At the dose escalation stage, all patients of different subtypes were mixed into the group. Without distinguishing between groups, the dose escalation of group A was given priority. After obtaining certain data, the dose escalation of group B was performed (fig.it can receive other research data of the same indication of this product). If the starting dose of group A (3.0 × 10\^8) meets the dose reduction standard according to the i3+3 principle (the i3+3 decision table indicates "d" or "Du", refer to the incremental decision table of the i3+3 principle for details), the investigator and the funder will jointly discuss and decide whether to enter the decreasing dose of 1.5 × 10\^8. If the maximum dose currently set is not confirmed as the possible recommended dose (RD), the investigator and the funder can jointly decide whether to increase it to a higher dose to explore the possible recommended therapeutic dose. During the study, the dose group may be increased or decreased or the dose may be extended according to the safety, effectiveness and cellular metabolic dynamics data of the study participants.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
The active ingredient of the drug in this study is the chimeric antigen receptor targeting cd19/cd20 (car-cd19/cd20 for short) modified allogeneic T cells. In order to reduce the rejection of GVHD and host immune cells, TCR and B2M were knocked out, and the related modifications were also carried out to reduce the host NK cell immune rejection.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGThe number and severity of dose-limiting toxicity (DLT)events
DLT was collected to explore the maximum tolerated dose (MTD) and / or dose range of CT1190B
Time frame: Within 28 days after cell infusion
Frequency, type and severity of AES
The frequency, type and severity of adverse events (AES) were collected. All adverse events will be evaluated according to the common terminology criteria for adverse events (CTCAE, version 5.0).
Time frame: Within 12 months after cell infusion
Investigator assessed objective response rate (ORR)
Time frame: The evaluation was performed within 12 months after cell infusion, such as 4 weeks, 8 weeks, 12 weeks, 4 months, 6 months, 9 months, 12 months after cell infusion
Investigator assessed complete response rate (CRR)
Time frame: The evaluation was performed within 12 months after cell infusion, such as 4 weeks, 8 weeks, 12 weeks, 4 months, 6 months, 9 months, 12 months after cell infusion
Investigator assessed proportion of minimal residual disease negative (MRD)
Time frame: The evaluation was performed within 12 months after cell infusion, such as 4 weeks, 8 weeks, 12 weeks, 4 months, 6 months, 9 months, 12 months after cell infusion
Investigator assessed duration of remission (DOR)
Time frame: The evaluation was performed within 12 months after cell infusion, such as 4 weeks, 8 weeks, 12 weeks, 4 months, 6 months, 9 months, 12 months after cell infusion
Investigator assessed time to remission (TTR)
Time frame: The evaluation was performed within 12 months after cell infusion, such as 4 weeks, 8 weeks, 12 weeks, 4 months, 6 months, 9 months, 12 months after cell infusion
Investigator assessed time to complete remission (TTCR)
Time frame: The evaluation was performed within 12 months after cell infusion, such as 4 weeks, 8 weeks, 12 weeks, 4 months, 6 months, 9 months, 12 months after cell infusion
Investigator assessed • event free survival (EFS)
Time frame: The evaluation was performed within 12 months after cell infusion, such as 4 weeks, 8 weeks, 12 weeks, 4 months, 6 months, 9 months, 12 months after cell infusion
Overall survival (OS)
Time frame: The evaluation was performed within 12 months after cell infusion, such as 4 weeks, 8 weeks, 12 weeks, 4 months, 6 months, 9 months, 12 months after cell infusion
The level of CT1190B gene copy number
Cell metabolic dynamics analysis will be carried out according to different treatment groups. According to the actual blood collection time, individual ct1190b cell copy number time curves (linear and semi logarithmic) were drawn. According to the blood collection time, the average and median ct1190b cell copy number time curves (linear and semi logarithmic) were drawn.
Time frame: Day 0 before cell infusion, Day 1, Day 3, Day 7, Day 10, Day 14, Day 18 (optional), Week 3, Week 4, Week 8, Month 4 and Month 6 after cell infusion
Duration of CT1190B gene copy number
Cell metabolic dynamics analysis will be carried out according to different treatment groups. According to the actual blood collection time, individual ct1190b cell copy number time curves (linear and semi logarithmic) were drawn. According to the blood collection time, the average and median ct1190b cell copy number time curves (linear and semi logarithmic) were drawn.
Time frame: Day 0 before cell infusion, Day 1, Day 3, Day 7, Day 10, Day 14, Day 18 (optional), Week 3, Week 4, Week 8, Month 4 and Month 6 after cell infusion
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