A Clinical Study to Investigate the Safety, Efficacy, and Cellular Metabolism of CT1190B CAR-T Cell therapy, in Patients with Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma.

This is a single-arm, open-label, dose exploratory clinical study to evaluate the safety, efficacy, cellular pharmacokinetics, and pharmacodynamics of CT1190B cells in patients with B-NHL. It is planned to enroll 6-24 participants.

Inclusion Criteria:

1. Participants must voluntarily sign the informed consent form (ICF) and must be willing and be able to adhere to the study visit schedule and other protocol requirements and agree to be in long term follow-up (LTFU) for up to 15 years as mandated by the regulatory guidelines.
2. 18-75 years old;
3. Histologically or cytologically confirmed B-NHL, according the 5th edition of the WHO classification of haematolymphoid tumours, including:

1) Cohort A1: Large B-cell lymphoma, including diffuse large B-cell lymphoma not other specified (DLBCL, NOS), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, transformed follicular large B-cell lymphoma (FLBL)/Grade 3b follicular lymphoma ( FL) ; 2) Cohort A2: Mantle cell lymphoma (MCL); 3) Cohort B1: Grade 1 ~ 3a FL; 4) Cohort B2: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) according to iwCLL2018 diagnose criteria , with the exception of participants who are currently transformed into Richter 's syndrome; 5) Cohort C:Primary central nervous system lymphoma （PCNSL). 4. Previous treatment requirement:

1. Cohort A1: Previously received at least 2 lines of systemic therapy, including anti-CD20 drugs (unless the investigator had determined that the tumor is/is CD20 negative) and anthracycline containing regimens, anti-CD20 drugs maintenance alone will not be counted as 1 line of treatment; for participants with transformed FL (FLBL), any treatment administered prior to transformation will not be counted as a prior line.
2. Cohort A2: at least 2 prior lines of systemic therapy, including anthracycline or bendamustine-containing chemotherapy, anti-CD20 drugs ( unless the investigator had determined that the tumor is/is CD20 negative) and a BTK inhibitor; and CD20 monoclonal antibody alone will not be count as 1 line of treatment;
3. Cohort B1: previously received at least 2 lines of systemic therapy, including anti-CD20 drugs ( unless the investigator had determined that the tumor is/is CD20 negative) and anthracycline-containing chemotherapy regimens, and CD20 monoclonal antibody alone will not be counted as 1 line of treatment;
4. Cohort B2: at least 2 prior lines of therapy, including immunotherapy or chemotherapy and a BTK inhibitor, or BTK inhibitor who are not suitable for immunotherapy or chemotherapy.
5. Cohort C:at least 1 line of therapy, including MTX based chemotherapy. 5. Intolerance to last treatment, or have progressed on or after the last treatment and currently require therapy.

6. At least one of the following:

1) CT or MRI testing: Intranodal lesions > 1.5 cm in long diameter, or Extranodal lesions > 1.0 cm in long diameter; 2)PET-CT testing: [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion per Lugano criteria at screening (Deauville score 4 or 5); 3) CLL participants requiring treatment according to iwCLL criteria (refer to Appendix 4); 7. Expected survival > 12 weeks; 8. Eastern Cooperative Oncology Group (ECOG) score 0-1,PCNSL ECOG score: 0~3; 9. Participants should meet the following test results

1. CBC: # platelet (PLT) ≥ 75 × 10 9/L (for participants with bone marrow or peripheral blood involvement: PLT ≥ 50 × 10 9/L), #hemoglobin (Hb) ≥ 80 g/L (for participants with bone marrow or peripheral blood involvement: Hb ≥ 60 g/L);
2. Endogenous creatinine clearance ≥ 30 mL/min (using the Cockcroft -Gault formula);
3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN and total bilirubin ≤ 1.5 × ULN ; if there is liver involvement: AST and ALT ≤ 5 × ULN and total bilirubin ≤ 3.0 × ULN ;
4. International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.

10. Female participants of childbearing potential must have a negative pregnancy test at screening and prior to receiving preconditioning therapy and are willing to use a highly effective and reliable method of contraception for 1 year after receiving study treatment and are absolutely prohibited from donating eggs for 1 year after receiving study treatment infusion during the study; male participants are willing to use a highly effective and reliable method of contraception for 1 year after receiving study treatment if they are sexually active with a female of childbearing potential. Sperm donation is absolutely prohibited for 1 year after receiving study treatment infusions during the study for all male participants.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Has HIV, syphilis infection, active hepatitis B virus infection (HBV-DNA above the detection limit), or active hepatitis C virus infection (HCV antibody and HCV-DNA positive);
3. Has any current uncontrolled active infection, including but not limited to participants with active tuberculosis (investigator 's judgment);
4. Participants' toxicities caused by previous treatment did not recover to Common Terminology Criteria for Adverse Events (CTCAE) ≤ Grade 1, except alopecia and other events that are judged tolerable by the investigator;
5. Autologous stem cell transplantation within 12 weeks prior to signing informed consent;
6. Prior therapy targeting CD19 (unless CD19 or CD20 target remains positive) ;
7. Has received treatment for the disease within 14 days or 5 half-lives (Based on a shorter period of time ) before FC, including but not limited to cytotoxic therapy, monoclonal antibodies or ADCs, targeted therapy, radiotherapy, epigenetic therapy, or investigational agents, or invasive investigational medical devices within 14 days before informed consent. If the radiation field covers ≤ 5% of the bone marrow reserve, the participant is eligible regardless of the end date of radiotherapy;
8. Systemic glucocorticoids equivalent to > 15 mg/day prednisone within 7 days prior to informed consent, with the exception of topical glucocorticoids;
9. Vaccination with live attenuated vaccines, inactivate vaccines or RNA vaccines within 4 weeks prior to informed consent;
10. Participants who are allergic or intolerant to preconditioning drugs, tocilizumab, or allergic to the components (DMSO) in CT1190B cell infusion preparation; or have other previous history of severe allergy such as anaphylactic shock;
11. Participants with any of the following cardiac conditions within 6 months prior to screening:

1) New York Heart Association (NYHA) Class III or IV heart failure; 2) Myocardial infarction, coronary artery bypass graft surgery, or unstable angina within 6 months before screening; 3) History of clinically significant uncontrolled arrhythmia, e.g., ventricular arrhythmia; 4) History of severe non-ischemic cardiomyopathy; 5) Left ventricular ejection fraction (LVEF) < 45% as assessed by echocardiogram or multimodal acquisition (MUGA) scan; 6) Other cardiac diseases that, in the opinion of the investigator, may jeopardize the participant 's well-being due to participation in this clinical study; 12. Oxygen saturation < 92%, or suffering from other serious lung diseases, which may endanger the participant 's life as judged by the investigator; 13. Presence of a second primary malignancy requiring treatment or not in complete remission within the past 2 years, except for the following successfully treated tumors with low malignancy such as non-metastatic basal cell or squamous cell skin cancer, non-metastatic prostate cancer, breast or cervical carcinoma in situ, non-muscle-invasive bladder cancer, or thyroid cancer; 14. Major surgery within 2 weeks before informed consent or planned during the study period or within 4 weeks after giving study treatment (excluding local anesthesia such as cataract); 15. Participants are unable or unwilling to comply with the requirements of the study protocol or are otherwise unsuitable for participating in this clinical study in the investigator 's assessment,;