This is a single-center, non-randomized and dose-escalation study to evaluate the safety and efficacy of C-CAR066 in treatment of r/r DLBCL who received CD19 CAR-T therapy.

This study plans to enroll 10 patients to assess the safety and efficacy of C-CAR066. Subjects who meet the eligibility criteria will receive a single dose of C-CAR066 injection.

The study will include the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation, Lymphodepleting Chemotherapy), C-CAR066 infusion and Follow-up Visit.

Inclusion Criteria:

1. The patient volunteered to participate in the study, and signed the Informed Consent
2. Age 18-75 years old, male or female
3. Patients diagnosed with diffuse large B-cell lymphoma (DLBCL, De novo or transformed) histologically according to the 2016 WHO Classification, at least one measurable lesion(LDi≥1.5 cm)
4. r/r DLBCL patients who received prior CD19 CAR-T therapy, and positive for CD20
5. At least 2 weeks from last treatment (radiation, chemotherapy, mAb, etc) to apheresis
6. Adequate organ and bone marrow fuction
7. No contraindications of apheresis
8. Expected survival time > 3 months
9. ECOG scores 0 - 1

Exclusion Criteria:

1. Have a history of allergy to cellular products

2. Patients with cardiac insufficiency classified as Class III or IV according to the New York Heart Association (NYHA) Heart Function Classification Standard

3. A history of craniocerebral trauma, consciousness disorder, epilepsy, cerebral ischemia or hemorrhagic cerebrovascular disease

4. Patients with active CNS involvement

5. Patients with autoimmune disease, immunodeficiency, or other treatment requiring inhibitors

6. Severe active infection (except simple urinary tract, bacterial pharyngitis), or currently receiving intravenous antibiotics. However, prophylactic antibiotics, antiviral and antifungal treatments are allowed

7. Live vaccination within 4 weeks before peripheral blood apheresis

8. HIV, HBV, HCV and TPPA / RPR infections, and HBV carriers

9. Have a history of alcoholism, drug addiction and mental illness

10. Non-sterile subjects had any of the following: a) being pregnant / lactating; or b) having a pregnancy plan during the trial; or c) having fertility without taking effective contraception

11. Patients with severe fludarabine or cyclophosphamide hypersensitivity

12. The patient has a history of other primary cancers, except for the following:

    1. Non-melanoma such as skin basal cell carcinoma cured by resection
    2. Cured carcinoma in situ such as cervical, bladder or breast cancer

13. The investigators believe that there are other circumstances that are not suitable for the trial