This is an open-label, multicenter, dose-escalation phase 1 study to determine the Safety and Efficacy of BZ019 in relapsed or refractory CD19+ B-cell Lymphoma subjects.
This is an open-label, multicenter, phase 1 study to determine the safety, PK, and antitumor activity of BZ019 in adult subjects with R/R large CD19+B cell lymphoma. The safety and efficacy of a single dose of different target doses of BZ019 will be evaluated in the dose-escalation phase and dose-expansion phase. Primary objectives: \- To evaluate the safety and tolerance of single infusion of BZ019 in adult patients with relapsed or refractory large B-cell lymphoma, and to determine the maximum tolerable dose (MTD) and phase II recommended dose. Secondary objectives: * To evaluate the pharmacokinetics and survival of BZ019 in the peripheral blood of adult patients with relapsed or refractory large B-cell lymphoma; * To evaluate the Pharmacodynamic characteristics of BZ019 in adult patients with relapsed or refractory large B-cell lymphoma; * Objective response rate (ORR), Overall survival, progression free survival, event free survival, and tumor progression time were used to evaluate the antitumor efficacy of BZ019 in the treatment of relapsed or refractory large B-cell lymphoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
A treatment program will include lymphodepleting chemotherapy with fludarabine and cyclophosphamide (flu/cy) followed by single-dose of BZ019 administered intravenously (IV).
Hematology Hospital, Chinese Academy of Medical Sciences
Tianjin, China
RECRUITINGTianjin medical university cancer institute and hospital
Tianjin, China
RECRUITINGDose-limiting toxicity (DLT)
Safety
Time frame: After 28 days of single infusion
Maximum tolerated dose (MTD)
Tolerability
Time frame: After 28 days of single infusion
Pharmacokinetics(the copies of cells in vivo)
Pharmacokinetics is defined as the number of copies of BZ019 DNA in peripheral blood at each visit after infusion until the test results are negative or below the detection limit. It aims to calculate the Peak Plasma Concentration (Cmax)
Time frame: Month 24
Pharmacokinetics(the duration of survival of cells in vivo)
Duration of BZ019 persistence is the period from the day of infusion to the first negative test result. It aims to calculate the area under the plasma concentration versus time curve (AUC)
Time frame: Month 24
Pharmacodynamics
Pharmacodynamics is defined as the level of Cytokine, at least include IL-2, IL-4, IL-6, IL-10, IL-15, IFN-γ, TNF-α. The peak value of cytokines and their return to baseline were evaluated
Time frame: After 28 days of single infusion
Antitumor efficacy-Objective response rate (ORR)
The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%)
Time frame: Month 24
Antitumor efficacy-Overall survival (OS)
The period from the first infusion to any cause of death
Time frame: Month 24
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Antitumor efficacy-Progression-free survival (PFS)
The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first.
Time frame: Month 24
Antitumor efficacy-event -free survival (EFS)
Event free survival rate refers to the time from enrollment to occurrence of any event, including death, disease progression, change of chemotherapy program, change to chemotherapy, additional treatment, occurrence of lethal or intolerable side effects and other events.
Time frame: Month 24
Antitumor efficacy- Tumor progression time (TTP)
Tumor progression time refers to the time from the beginning of the infusion of cells to tumor progression
Time frame: Month 24