A Clinical Trial of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory Diffuse Non-Hodgkin Lymphoma

Inclusion Criteria

• •1. Informed consent is signed by the subject.
• •2. Age 18 to 75.
• •3. Relapsed or refractory NHL with CD19-positive after at least two systemic lines of therapy
• •a. Diffuse large B cell lymphoma (DLBCL) non-specific (NOS), T-cell / Histiocyte Rich large B-cell lymphoma, elderly EBV-positive diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma (PMBCL), chronic inflammation-associated DLBCL, follicular lymphoma (FL) transformed large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and / or BCL6 rearrangement and High-grade B-cell lymphoma-unspecified; b. Chemotherapy-refractory disease, defined as one of more 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 at least 4 courses of first-line treatment / at least 2 courses of end-line treatment (2 lines and above) with duration no longer than 6 month from last dose of therapy OR;
• •* Refractory post-autologous stem cell transplant (ASCT); i. Disease progression or relapsed less than or equal to 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; Any BM relapse after autologous stem cell transplantation (ASCT); c. Individuals must have received two systemic lines of therapy
• •* anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative;
• •* an anthracycline containing chemotherapy regimen;
• •* FL-transformed DLBCL must have received pre-chemotherapy for FL and become resistant after conversion to DLBCL.
• •4. At least one measurable lesion, defined as at least 1 lymph node \>1.5 cm in the longest diameter, per revised IWG Response Criteria.
• •5. Any previous systemic immune checkpoint therapy (such as anti-PD1 / PD-L1 monoclonal antibody, etc.), at least 3 half-lives away from the Cell Product Preparation; other systemic treatments should be stoped at least 2 weeks or 5 half-lives before Cell Product Preparation (shorter Whichever comes first).
• •6. Eastern cooperative oncology group (ECOG) performance status of 0 to 1.
• •7. Sufficient bone marrow reserves defined as:
• •1. Absolute neutrophil (ANC) \> 1,000 / mm3;
• •2. Lymphocyte absolute value (ALC) ≥ 100 / mm3;
• •3. Platelet (PLT) ≥ 50,000 / mm3.
• •8. Adequate organ function defined as:
• •1. aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN);
• •2. Serum alanine aminotransferase (ALT) ≤ 3 upper limit of normal (ULN);
• •3. Total bilirubin ≤ 2 ULN, except in individuals with Gilbert's syndrome; Note: Patients with Gilbert's syndrome that bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN will be eligible;
• •4. A serum creatinine≤ 1.5 ULN or Creatine removal rate ≥ 60mL/min (Cockcroft and Gault);
• •5. Must have a minimum level of pulmonary reserve as ≤ Grade 1 dyspnea and oxygen saturation \> 91% on room air;
• •6. International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (APTT) ≤ 1.5 ULN;
• •9. Non-hematological toxic reactions (excluding diseases related) caused by previous treatment were restored to ≤ 1 level before screening (excluding ≤ 2 level of neurotoxicity caused by hair loss and chemotherapy drugs).
• •10. Women of childbearing age have a negative blood / urine pregnancy test within 7 days before the CNCT19 infusion. Women of child-bearing potential and all male participants must use highly effective methods of contraception throughout the study and for a period of at least six months after the CNCT19 infusion.