CNCT19 Following ASCT in Patients With Relapsed or Refractory B-cell Lymphoma
CNCT19 Following ASCT in Patients With Relapsed or Refractory B-cell Lymphoma
The primary objective of this study is to explore the safety and efficacy of CNCT19 (a
 second-generation anti-CD19 CAR T-cell using 4-1BB as co-stimulatory domain provided by
 Juventas, Tianjin, China) infusion following ASCT in patients with relapsed or refractory
 B-cell lymphoma.
This is a single-center, non-randomized, open-label, prospective clinical trial to evaluate
 the safety and efficacy of CNCT19 infusion following high-dose chemotherapy and autologous
 stem-cell transplantation (HDT/ASCT) in patients with relapsed or refractory B-cell lymphoma.
 CNCT19 cells will be infused on day +3 (±1d) with a fixed dose of 2×10^6/kg. The study will
 assess the safety and efficacy of this combinational therapy, including the incidence and
 severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity
 syndrome (ICANS), hematological, and other non-hematological toxicities, and objective
 response rates and complete response rates and survivals of the subjects.
Key Inclusion Criteria:

 1. Histologically confirmed large B-cell lymphoma including the following types

 -  diffuse large B-cell lymphoma

 -  high-grade B-cell lymphoma with or without MYC and BLC2 and/or BCL6 rearrangement

 -  transformed lymphoma

 2. Relapsed or refractory diseases fulfilling one of the following criteria (individuals
 must have received anti-CD20 monoclonal antibody and anthracycline-containing
 chemotherapy regimen)

 -  Primary refractory disease, defined as disease progression after first-line
 immunochemotherapy or disease progression within 6 weeks of the end of the last
 chemotherapy

 -  Stable disease (SD) as best response after at least 4 cycles of first-line
 therapy

 -  Partial response (PR) as best response after at least 6 cycles of first-line
 therapy (biopsy-proven residual disease is needed for individuals with Deauville
 score of 4)

 -  PR as best response after at least 2 cycles of second-line therapy

 -  Disease relapse ≤12 months after the completion of first-line immunochemotherapy

 -  Relapsed or refractory disease after ≥2 lines of chemotherapy

 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

 4. Adequate bone marrow function as evidenced by:

 -  Absolute neutrophil count (ANC) ≥ 1000/uL

 -  Platelet count≥ 75,000/uL

 5. Adequate renal and hepatic function defined as:

 -  Serum alanine aminotransferase (ALT/AST) ≤ 3 upper limit of normal (ULN)

 -  Total bilirubin ≤1.5 mg/dL, except in individuals with Gilbert's syndrome

 -  Serum creatinine ≤2 ULN, or creatinine clearance (as estimated by Cockcroft
 Gault) ≥ 40 mL/min

 6. Cardiac ejection fraction ≥ 50%

 7. Baseline oxygen saturation > 92% on room air

 8. Life expectancy ≥3 months

 Key Exclusion Criteria:

 1. Active Central Nervous System (CNS) involvement by lymphoma

 2. History of autologous or allogeneic stem cell transplantation

 3. Active HBV or HCV infection, defined as HBV-DNA or HCV-DNA levels above the normal
 upper limit, with or without abnormal liver function. Individuals with positive HBsAg
 or HBcAb should receive antiviral prophylaxis for at least 12 months after CNCT19
 infusion.

 4. Presence of uncontrolled infection, cardio-cerebrovascular disease，coagulopathy, or
 connective tissue disease.

 5. History of seizure or other CNS disorder

 6. History of HIV infection