The objective of this study was to evaluate the safety and efficacy of CD180 CART cells in the treatment of patients with relapsed/refractory CD180-positive hematological malignancies. In this single-arm, open-label, single-center, Phase I clinical trial, two cohorts were set up: (1) relapsed and refractory AML cohort; and (2) relapsed and refractory B-ALL/LBL cohort. CD180 CART cells will be administered intravenously using a 3+3 dose escalation and rapid titration design, with CART dose groups of (1) 0.5×10\^6 CART cells/kg;(2)1×10\^6 CART cells/kg; and (3) 3×10\^6 CART cells/kg. Each cohort was planned to enroll 6-12 patients.
This study will utilize CD180 CART cells to treat CD180-positive relapsed or refractory hematological malignancies, especially AML and B-ALL/LBL patients. Two cohorts were established: (1) relapsed and refractory AML cohort; and (2) relapsed and refractory B-ALL/LBL cohort. A 3+3 dose escalation and rapid titration design was used to explore the maximum tolerated dose for each cohort. 3+3 dose escalation CART 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 6 and a maximum of 12 patients are expected to be enrolled in each cohort. Fludarabine and cyclophosphamide-based preconditioning should be performed within 1 week prior to CD180 CART infusion. CD180 CART can be infused on D-1 provided that the requirement of 24 hours after completion of preconditioning is met. The objective of the study was to evaluate the safety and efficacy of CD180 CART cells in the treatment of patients with relapsed/refractory CD180-positive hematological malignancies.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Subjects screened to meet the requirements for CD180 CART use will enter clinical trials. Subjects were assessed at baseline. Fludarabine and cyclophosphamide based preconditioning should be performed within 1 week prior to CD180 CART infusion: fludarabine (Flu) 30mg/m2 ×3 days; cyclophosphamide (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 VP-16. Infusion of CD180 CART must be performed 24 hours after completion of chemotherapy preconditioning. CD180 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 CD180 CART cells, or life-threatening hematological or non-hematological toxicity.
Time frame: 3 months after CD180 CART cells infusion
Number of adverse event of CD180 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: within 3 months after CD180 CART cells infusion
Duration of remission (DOR)
Time to first CR/CRi + PR (B-ALL/LBL) or CRc + PR (AML) to disease relapse or death due to leukemia after CD180 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 frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
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