Treatment of Refractory/Relapsed Non-Hodgkin Lymphoma With TriCAR-T_CD19

TriCAR-T-CD19 Adoptive Immunotherapy for CD19-positive Refractory/Relapsed Non-Hodgkin Lymphoma

This is a single arm, open-label, single-center, phase 1/2 study, to determine the safety and efficacy of TriCAR-T-CD19, an autologous tri-functional anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in refractory/Relapsed Non-Hodgkin Lymphoma (NHL).

The tri-functional anti-CD19 chimeric antigen receptor contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the TriCAR-T-CD19 to simultaneously targeting the CD19 positive NHL，blocking the inhibitory PD-L1 signal and stimulating T/NK cell activation and expansion.

Inclusion Criteria:

1. All subjects must personally sign and date the consent form before initiating any study specific procedures or activities;
2. All subjects must be able to comply with all the scheduled procedures in the study;
3. Histologically or cytologically confirmed CD19 positive non-Hodgkin lymphoma;
4. Chemotherapy-refractory disease, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in the standard R-CHOP or CHOP chemotherapy; Disease progression or relapsed in ≤12 months of ASCT (must have biopsy proven recurrence in relapsed subjects); If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy.
5. No available standard therapy;
6. At least one measurable lesion per revised IWG Response Criteria;
7. Aged 18 to 68 years;
8. Expected survival ≥12 weeks;
9. Eastern cooperative oncology group (ECOG) performance status of ≤2;
10. Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks;
11. All other treatment induced adverse events must have been resolved to ≤grade 1;
12. Laboratory tests must fulfill the following criteria: ANC ≥ 1000/uL, HGB >70g/L, Platelet count ≥ 50,000/uL, Creatinine clearance ≤1.5 ULN, Serum ALT/AST ≤2.5 ULN, Total bilirubin ≤1.5 ULN (except in subjects with Gilbert's syndrome);
13. Female must be not pregnant during the study.

Exclusion Criteria:

1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years;
2. History of allogeneic stem cell transplantation;
3. Prior other CAR therapy or other genetically modified T cell therapy;
4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment;
5. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases;
6. Lactating women;
7. Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive);
8. Subjects need systematic usage of corticosteroid;
9. History of any gene therapy;
10. Subjects need systematic usage of immunosuppressive drug;
11. Known history of infection with HIV;
12. Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study;
13. Other reasons the investigator think the patient may not be suitable for the study.