Phase 1/2 Study of CD19 Chimeric Antigen Receptor T-cell (CD19 CAR-T; PL001) for Relapsed or Refractory B-cell Lymphoma

Exclusion Criteria51

• Screening 1:
• Chronic lymphocytic leukemia with Richter's transformation.
• Primary CNS lymphoma. (Non-primary CNS lymphoma with CNS involvement is eligible).
• Primary intra-ocular lymphoma.
• Prior CD19 targeted therapy, such as CAR-T, Bi-specific T-cell engagers (BiTE), or monoclonal antibody.
• History of cancers (includes myelodysplastic syndrome) other than non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless disease-free without active treatment for at least 3 years.
• History of allogeneic HSCT.
• History of autologous HSCT within 3 months prior to consent.
• Received any investigational product within 4 weeks prior to consent.
• Systemic anticancer therapy within 3 weeks prior to apheresis.
• Long-term use of systemic corticosteroids, defined as daily use \>10 mg of prednisolone or equivalent, within 2 weeks prior to leukapheresis.
• Exception examples:
• Nasal, ophthalmic, inhaled, intra-articular, and topical steroid preparation.
• Short term systemic steroid for drug, contrast, or blood transfusion allergic reaction management.
• Low dose maintenance steroid therapy for other conditions (e.g., asthma).
• Use of long-acting and short-acting myeloid growth factor within 2 weeks, 5 days prior to leukapheresis, respectively.
• Received anti-thymocyte globulin within 4 weeks prior to consent.
• Intrathecal chemotherapy within 1 week prior to leukapheresis.
• Inadequate major organ functions at Screening, which were defined as any of below:
• absolute neutrophil count (ANC) \<500/µL
• Absolute lymphocyte count (ALC) \<300/µL, excluding leukemic cells.
• Hemoglobin (Hb) \<8.0 g/dL
• Platelet count \<75,000/µL without transfusion support within 3 days
• e. Baseline O2 saturation \<92% by pulse oximetry at room air
• Significant CNS diseases such as dementia, major stroke, seizure while under antiepileptic drug
• Aspartate aminotransferase (AST) \>5 × upper limit of normal (ULN) and alanine aminotransferase (ALT) \>5 × ULN, or total bilirubin \>2 × ULN (except for constitutional jaundice)
• Serum creatinine \> 1.5 × ULN and estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m², as calculated by the Cockcroft-Gault formula.
• Significant cardiac disease including but not limited to: left ventricular ejection fraction (LVEF) \<50%, QTc(the corrected QT interval) \> 480 msec based on Fredericia's formula, clinically significant arrhythmias, history of myocardial infarction or unstable angina within 3 months prior to consent.
• Active hepatitis B virus (HBV) infection defined as detectable HBV DNA (Patients with positive anti-hepatitis B core antibody \[HBcAb\] must consent to regular monitoring of HBV DNA, and anti-HBV prophylaxis with oral anti-viral agent (such as entecavir) is mandatory until End-of-Study visit \[Visit 15\].)
• Active hepatitis C virus (HCV) infection defined as positive anti- HCV antibody plus detectable HCV RNA.
• Positive for human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) infection.
• Uncontrolled acute life-threatening bacterial, viral, or fungal infection (e.g., the need for intravenous therapeutic antibiotics, blood culture positive ≤72 hours prior to apheresis).
• \. Any medical conditions which might compromise the patient's safety from leukapheresis, lymphodepletion chemotherapy, or CAR-T therapy and anticipated AEs, according to the Investigator's evaluation.
• Patients with insufficient leukapheresis cells.
• Screening 2:
• Inadequate major organ functions at Screening which were defined as any of below:
• ANC \<500/µL
• Hb \<8.0 g/dL
• Platelet count \<50,000/µL, without transfusion support within 3 days
• Baseline O2 saturation \<92% by pulse oximetry on room air
• AST \>5 × ULN and ALT\>5 × ULN, or total bilirubin \>2 × ULN (except for constitutional jaundice)
• Significant CNS diseases such as dementia, major stroke, seizure while under antiepileptic drug
• Serum creatinine \> 1.5 × ULN and estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m², as calculated by the Cockcroft-Gault formula.
• Long-term use of systemic corticosteroids, defined as daily use \>10 mg of prednisolone or equivalent.
• Exception examples:
• Nasal, ophthalmic, inhaled, intra-articular, and topical steroid preparation.
• Short term systemic steroid for drug, contrast, or blood transfusion allergic reaction management.
• Low dose maintenance steroid therapy for other conditions (e.g., asthma).
• Use of long-acting and short-acting myeloid growth factor within 12 days, 2 days prior to lymphodepletion therapy, respectively.
• Uncontrolled acute life-threatening bacterial, viral, or fungal infection (e.g. the need for intravenous therapeutic antibiotics, blood culture positive ≤72 hours prior to lymphodepletion).
• Any medical condition which might compromise the patient's safety because of lymphodepletion chemotherapy or CAR-T therapy and anticipated AEs, according to the Investigator's opinion.