This is an investigator-initiated, single-arm, open-label, non-randomised phase I clinical study. The objective of this trial is to evaluate the safety, tolerability and pharmacokinetics of donor-derived CD19 CAR Therapy bridged Allo-HSCT and sequential donor-derived CD22 CAR Therapy for r/r B-ALL and to explore the efficacy of this therapy preliminarily. The primary endpoints are incidence and type of dose-limiting toxicity (DLT) within 28 days (i.e., 43 days after donor-derived CD19 CAR T-cell infusion) after donor-derived CD19 CAR T-cell therapy bridged allogeneic haematopoietic stem cell transplantation; total number, incidence and severity of adverse events from donor-derived CD19 CAR T cell infusion back to 30 days after donor-derived CD22 CAR T cell infusion (i.e., within 120 days of donor-derived CD19 CAR T cell infusion). The secondary endpoints are total number, incidence and severity of adverse events from 120 days to 2 years after donor-derived CD19 CAR T-cell infusion; ORR(CR+CRi) on days 45, 90, 120; duration of response(DOR), event-free survival(EFS), overall survival(OS); pharmacokinetics characteristics. The trial plan to enroll 3\~12 cases in dose escalation phase and 36 cases in dose expansion phase.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Peripheral blood mononuclear cells for the production of CD19 CAR T cells and CD22 CAR T cells are collected from donors and haematopoietic stem cells are collected from donors.
Beijing GoBroad Hospital
Beijing, Beijing Municipality, China
RECRUITINGDose-limiting toxicity (DLT)
Incidence and type of dose-limiting toxicity (DLT) within 28 days (i.e., 43 days after donor-derived CD19 CAR T-cell infusion) after donor-derived CD19 CAR T-cell therapy bridging allogeneic haematopoietic stem cell transplantation will be recorded.
Time frame: Within 43 days of donor-derived CD19 CAR T-cell infusion
Adverse events (AEs)
Total number, incidence and severity of adverse events (AEs) from the time of donor-derived CD19 CAR T cell infusion back to 30 days after donor-derived CD22 CAR T cell infusion (i.e., within 120 days of donor-derived CD19 CAR T-cell infusion) will be recorded.
Time frame: Within 120 days of donor-derived CD19 CAR T-cell infusion
Long-term Adverse events (AEs)
Total number, incidence and severity of AEs from 120 days to 2 years after donor-derived CD19 CAR T-cell infusion will be recorded.
Time frame: From 120 days to 2 years after donor-derived CD19 CAR T-cell infusion
Objective response rate(ORR)
Objective response rate (ORR) at day 30, day 45, day 90 as determined by the National Comprehensive Cancer Network (NCCN) GuidelinesVersion 3.2023 of Acute Lymphoblastic Leukemia.
Time frame: day 30, day 45, day 90
Duration of response (DOR)
DOR is defined as the date when CR or CRi response criteria are first met to the date of relapse or death caused by ALL in the absence of documented relapse.
Time frame: Up to 2 years
Event-free survival (EFS)
EFS is defined as the time from donor-derived CD19 CAR T-cell infusion to the occurrence of any event, which includes disease progression, discontinuation of therapy for any reason, or death.
Time frame: Up to 2 years
Overall survival (OS)
OS is defined as the time from the infusion of donor-derived CD19 CAR T cells until death due to any cause.
Time frame: Up to 2 years
The persistence of CD19/CD22 CAR T cells.
The persistence of CD19/CD22 CAR T cells in cerebral spinal fluid (CSF) and peripheral blood will be detected by flowcytometry and qPCR after CD19/CD22 CAR T cells infusion.
Time frame: Up to 2 years
The Maximum concentration (Cmax) of CD19/CD22 CAR T cells.
The Maximum concentration (Cmax) of CD19/CD22 CAR T cells will be recorded.
Time frame: Up to 2 years
The time to maximum plasma concentration (Tmax) of CD19/CD22 CAR T cells.
The time to maximum plasma concentration (Tmax) of CD19/CD22 CAR T cells will be recorded.
Time frame: Up to 2 years
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