This is a single center, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of CD19-PD1-CART cells therapy for patients with relapsed/refractory B Cell Lymphoma.
Lymphoma is a malignant tumor originating from lymph nodes or other lymphoid tissues. It can be divided into B cells, T cells, and NK cell lymphomas depending on the origin of different lymphocytes. Among them, B cell lymphoma accounts for about 90% of lymphoma. Chimeric antigen receptor T (CART) cells is a promising treatment for lymphoma. T lymphocytes from patients are separated and engineered with CD19-CAR, to specifically recognize and eliminate CD19-positive tumor cells. At present, many CD19CART cells therapy studies are in the stage of clinical research and have achieved significant clinical effects. Although there are some CD9CART cells clinical trials, the therapeutic effect on lymphoma is significantly lower than that of acute leukemia. One of the reasons is that lymphoma has the nature of solid tumors, whichi has a certain immunosuppressive microenvironment. The clinical trials of anti-PD-1 antibody drugs against lymphoma also show good therapeutic efficacy. Therefore, the combination of anti-PD-1 or PD-L1 antibody and CD19CART is one of the ways to improve the therapeutic effect of CART cells. The investigators screened PD-1 mutants that have high bind with the PD-L1 ligand, and prepared CD19CART which secretes the mutant PD-1Fc fusion protein. Preclinical studies have shown that CD19CART cells secreting mutant PD-1Fc fusion protein have a superior killing effect to CD19CART cells which does not express PD-1 fusion protein. The trial was conducted to explore the safety and efficacy of CD19-PD1-CART cells in Relapsed/Refractory B Cell Lymphoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
This study was a single-center, open-label, single-arm, non-randomized clinical trial, which has 3 groups by infusion dose level. Firstly, each dose group has 3 patients. The pretreatment regimen of cyclophosphamide (25mg/m2 for 3 consecutive days) and fludarabine (10mg/kg for 3 consecutive days) was given before CART cells were reinfused. CART cells were reinfused on the third day after the pretreatment. If no serious side effects emerges in the group, then the next group uses the subsequent higher dose. If serious side effects emerges in a single patients in any dose level, 3 more patients will be enrolled to the same dose level. After 9 or more patients, the investigators select the safest dose and recruit more patients for CART test to explore its effectiveness.
Hai Nan Hospital of Chinese PLA General Hospital
Sanya, Hainan, China
RECRUITINGIncidence of Treatment-related Adverse Events
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).
Time frame: 3 years
Overall Remission Rate(ORR) of CD19-PD1-CART cells in Lymphoma
ORR will be assessed from the first CAR-T cell infusion to death or last follow-up
Time frame: 3 years
Overall survival(OS) of CD19-PD1-CART cells in Lymphoma
OS will be assessed from the first CAR-T cell infusion to death or last follow-up
Time frame: 3 years
Progress-free survival(PFS) of CD19-PD1-CART cells in Lymphoma
PFS will be assessed from the first CAR-T cell infusion to death or last follow-up
Time frame: 3 years
Rate of CD19-PD1-CARTcells in peripheral blood cells
In vivo (peripheral blood) rate of CD19-PD1-CART cells were determined by means of flow cytometry.
Time frame: 3 years
Quantity of CD19-PD1-CART cells copies in peripheral blood cells.
In vivo (peripheral blood) quantity of CD19-PD1-CART cells copies copies were determined by means of qPCR.
Time frame: 3 years
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