A Dose Escalating Study of CD19/CD22/BCMA CAR-T Therapy in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma(NHL)

Inclusion Criteria26

• Patients who are diagnosed with relapsed/refractory B cell non-Hodgkin lymphoma , especially
• Diffuse Large B Cell Lymphoma, not other specified (DLBCL,NOS),
• Primary Mediastinal Large B Cell Lymphoma (PMBCL)
• Transformation Follicular Lymphoma (TFL)
• High grade B-cell lymphoma(HGBCL)
• High grade B-cell lymphoma (HGBCL) with MYC(myelocytomatosis oncogene) and BCL2(B-cell lymphoma2) /BCL6 (B-cell lymphoma6) rearrangement
• Refractory diseases are defined as one of the following
• No response to last line of therapy: i. Progressive disease (PD) as best response to most recent therapy regimen; ii. Stable disease (SD) as best response to most recent therapy regimen
• Not candidate for autologous stem cell transplant (ASCT) or refractory post-ASCT: i. Disease progression (PD) or relapsed ≤12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy
• Individuals must have received adequate prior therapy including at a minimum:
• anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and
• an anthracycline containing chemotherapy regimen
• Immunohistochemical staining shows at least two of B cell surface receptor antigen CD19,CD20, BCMA are positive(including weak, medium and strong positive)
• At least one measurable lesion during the screening based on the recommendation for initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin lymphoma.
• Life expectancy ≥ 12 weeks
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1
• Adequate renal, hepatic, pulmonary and cardiac function defined as:
• Renal function: Serum creatinine ≤ 1.5 upper limit of normal(ULN), or eGFR ≥ 60 mL/min/1.73m2 \[eGFR(estimated glomerular filtration rate)=186×age\^-0.203×SCr\^-1.154（mg/dl）,female×0.742\]
• Hepatic function: i: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 ULN and ii: total bilirubin ≤ 2 ULN, except in individuals with Gilbert syndrome (in Gilbert's syndrome patients, those with total bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN can be enrolled).iii: International normalized ratio (INR) or prothrombin time (PT) ≤1.5 ULN Pulmonary: Have the minimum level of pulmonary reserve, defined as ≤ CTCAE (Common Terminology Criteria for Adverse Events) grade 1 dyspnea and the SaO2(oxygen saturation)≥ 91% on room air
• Cardiac: left ventricular ejection fraction (LVEF) ≥50% determined by echocardiogram(ECG) or multigated acquisition scan (MUGA)
• Adequate bone marrow function, define as:
• absolute neutrophil count (ANC) ≥1 ×10\^9/L
• absolute lymphocyte count (ALC)≥ 0.5 ×10\^9/L
• Platelets ≥50 ×109/L；
• Hemoglobulin ≥80 g/L; patients with bone marrow involvement can be enrolled if globulin\>60 g/L
• Female of child-bearing age and male participants must agree to use effective contraceptive methods until no CAR-T cells can be detected by PCR(polymerase chain reaction) test.