treatment of refractory/relapsed non-hodgkin lymphoma with tricar-t_cd19

Conditions: Non-hodgkin Lymphoma,B Cell

Summary: 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.

Eligibility criteria:
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.

Keywords: cd19 car-t tricar-t-cd19 non-hodgkin lymphoma nhl