This is a single-center, open-label study to evaluate the safety and efficacy of C-CAR039 in relapsed and/or refractory B-NHL patients.

This is a single-arm, open label, phase I study to evaluate the safety and preliminary efficacy of C-CAR039 in adults with relapsed/refractory B-cell Non-Hodgkin's Lymphoma. 10 patients are planned to be enrolled. Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of C-CAR039. Following manufacture of the drug product, subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide prior to C-CAR039 infusion. All subjects who have received C-CAR039 infusion will be followed for up to 24 months

Inclusion Criteria:

1. Age 18-70 years (include 18 and 70), male or female;
2. Expected survival ≥ 12 weeks
3. ECOG score 0-2
4. CD19 or CD20 positive B-NHL confirmed by cytology or histology according to WHO2016 criteria, including DLBCL, PMBCL, tFL, FL and MCL;
5. Relapsed or refractory disease after ≥ 2 lines (for FL, at least 3 lines) of standard therapy or relapsed after autologous stem cell transplantation (ASCT)
6. For CD20-positive subjects, they should have received at least one regimen containing anti-CD20-targeted therapy (such as rituximab). If they do not complete the regimen due to intolerance, the cause of intolerance should be recorded;
7. No contraindications of apheresis.
8. At least one measurable lesion according to Lugano 2014 criteria;
9. Adequate organ and bone marrow function.
10. The patient volunteered to participate in the study and signed the Informed Consent;

Exclusion Criteria:

1. Malignant tumors other than B-NHL within 5 years prior to screening, except cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery;
2. Active HIV, HBV, HCV or treponema pallidum infection ;
3. Any instability of systemic disease, including but not limited to active infection (except local infection), severe cardiac, liver, kidney, or metabolic disease need therapy;
4. Any uncontrolled active disease that prevents participation in the trial
5. Any situation that the investigator believes will harm the safety of the subjects or interfere with the purpose of the study
6. Female subjects who have been pregnant or breastfeeding, or who plan to conceive during or within 1 year after treatment, or male subjects' partner plans to conceive within 1 year after C-CAR039 infusion;
7. Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment;
8. Patients who have been previously infected with tuberculosis;
9. Administered Corticosteroids and/or other immunosuppressants within 7 days before apheresis. and 5 days before the infusion of C-CAR039;
10. Patients with central nervous system involvement;
11. Any systemic antitumor therapy performed within 2 weeks before enrollment;
12. Those with medical conditions that prevent them from signing the written informed consent or from complying with the study procedures; or those who are unwilling or unable to comply with the study requirements;
13. Other conditions was considered unsuitable for enrollment by the investigator.