This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous chimeric antigen receptor T (CAR-T) cells targeting CD19/CD22/BCMA in patients with relapsed or refractory B cell non-Hodgkin lymphoma.
This is a single arm, open-label, dose escalation investigator initiated (IIT) study, the primary objective is to evaluate the safety and tolerability of CD19/CD22/BCMA CAR-T therapy in patients with B cell non-Hodgkin lymphoma, and determine the maximum tolerated dose (MTD). For the secondary objectives, pharmacokinetics(PK), survival of CAR-T cells in vivo, pharmacodynamics (PD) and efficacy in R/R B cell NHL will be evaluated. This study flow comprises of a screening phase( ≤28 days prior to apheresis), apheresis phase (occur upon enrollment, ≤10 days prior to infusion), lymphodepletion phase (from Day -5 to Day -3) ,infusion of CD19/CD22/BCMA CAR-T cells on Day0, DLT assessments phase from Day1 to Day 28 and post-treatment follow-up phase (Day 29 and up to end of the study).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CD19/CD20/BCMA CAR T cells. Cyclophosphamide and fludarabine will be given from day-5 to day-3 before the infusion for lymphodepletion. On day0 subjects will receive one dose treatment with CD19/CD20/BCMA CAR T cells by intravenous (IV) injection
Mengchao Cancer Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGDose-limiting toxicity(DLT)
Safety
Time frame: Day0-Day28
Maximum tolerated dose (MTD)
Tolerability
Time frame: Day0-Day28
Maximum Plasma Concentration(Cmax)
Pharmacokinetics (PK)
Time frame: Day0-Day28,Day0-undetectable for CAR positive T cells
Maximum Plasma Concentration Time (Tmax)
Pharmacokinetics (PK)
Time frame: Day0-Day28,Day0-undetectable for CAR positive T cells
Area Under Curve (AUC)
Pharmacokinetics(PK)
Time frame: Day0-Day28,Day0-undetectable for CAR positive T cells
CAR positive T cells
Pharmacokinetics(PK)
Time frame: Day0-Day28,Day0-undetectable for CAR positive T cells
Cytokines ( IL(interleukin)-2, IL-4, IL-6, IL-8, IL-10, IL-15, IFN(interferon)-γ, TNF(tumor necrosis factor)-α and MCP( monocyte chemoattractant protein)-1)
Pharmacodynamics (PD)
Time frame: Day0-Day28
Overall survival (OS)
Clinical response assessed by Lugano Response Criteria for non-Hodgkin Lymphoma
Time frame: Day28,Month2,Month3,Month6,Month9,Month12,Month18,Month24
Progression-free survival (PFS)
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Clinical response assessed by Lugano Response Criteria for non-Hodgkin Lymphoma
Time frame: Day28,Month2,Month3,Month6,Month9,Month12,Month18,Month24