The aim of this study was to evaluate the safety and efficacy of universal CD7 CART (uCD7 CART) cells in the treatment of patients with relapsed/refractory CD7-positive hematologic malignancies. In this single-arm, open-label, single-center, Phase 1 clinical trial, two cohorts were set up: (1) relapsed and refractory acute myeloid leukemia (AML) cohort; and (2) relapsed and refractory T lymphoblastic leukemia/lymphoma (T-ALL/LBL) cohort. Each cohort was planned to enroll 4-12 patients. uCD7 CART cells will be administered intravenously to explore the maximum tolerated dose (MTD) of each cohort using a 3+3 dose escalation and rapid titration design.
This study will use universal CD7 CAR-T cells to treat CD7-positive relapsed or refractory hematological malignancies, especially AML and T-ALL/LBL patients. Two cohorts were established: (1) relapsed and refractory AML cohort; and (2) relapsed and refractory T-ALL/LBL cohort. A 3+3 dose escalation and rapid titration design was used to explore the MTD for each cohort. 3+3 dose escalation CAR-T dose groups were (1) 0.5×10\^6 CART cells/kg; (2)1×10\^6 CART cells/kg;(3) 3×10\^6 CART cells/kg. A minimum of 4 and a maximum of 12 patients are expected to be enrolled. Fludarabine and cyclophosphamide-based preconditioning should be performed within 1 week prior to uCD7 CART infusion. uCD7 CART can be infused at D-1 if the requirement of 24 hours after completion of preconditioning is met. To evaluate the safety and efficacy of uCD7 CART cells in the treatment of patients with relapsed/refractory CD7-positive hematologic malignancies.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Subjects screened to meet the requirements for uCD7 CART use will enter clinical trials. Subjects were assessed at baseline. Fludarabine (Flu) and cyclophosphamide (CTX) based preconditioning should be performed within 1 week prior to uCD7 CART infusion: Flu 30mg/m2 ×3 days; CTX 500mg/m2 ×3 days. The investigator can adjust the pretreatment regimen appropriately according to the condition of the subject, such as increasing the dose of CTX to 600mg/m2 ×3 days, increasing the application of cytarabine and etoposide. Infusion of uCD7 CART must be performed 24 hours after completion of chemotherapy preconditioning. uCD7 CART can be infused at D-1 if the requirement of 24 hours after completion of preconditioning is met.
Institute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin Municipality, China
RECRUITINGDose-limiting toxicity(DLT) Any toxicity associated with uCD7 CAR-T cells, or life-threatening hematological or non-hematological toxicity.
Any toxicity associated with uCD7 CART cells, or life-threatening hematological or non-hematological toxicity.
Time frame: 3 months after uCD7 CART cells infusion
Number of adverse event of CD7 CART cells treatment
Time frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
Response rate in 3 months
Time frame: 3 months after uCD7 CART cells infusion
Duration of remission (DOR)
Time to first CR/CRi + PR (T-ALL/LBL) or CRc + PR (AML) to disease relapse or death due to leukemia after uCD7 CART infusion.
Time frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
Event-free survival (EFS)
Time frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
Leukemia-free Survival (LFS)
Time from first CR/CRi (ALL/LBL) or CRc (AML) to relapse or death.
Time frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
Proportion of patients receiving hematopoietic stem cell
Time frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
Overall survival (OS)
Time from the first infusion of uCD7 CART cells to death from any cause.
Time frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
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