CELL INTELLIGENCE · 肿瘤细胞治疗研究

Key Inclusion Criteria:

* Signed informed consent.
* Relapsed or refractory CD20+ diffuse large B-cell lymphoma, mantle cell lymphoma or indolent lymphoma.
* The patient should have been treated with at least two lines of therapy and have no curative treatment option, specifically

  * Relapsed or refractory CD20+ B-cell lymphoma that are not eligible to receive clinically approved CD19-directed CAR T cell treatment.
  * Relapsed or refractory CD20+ B-cell lymphoma who are CD19 negative.
  * Relapsed or refractory B-cell lymphoma who relapse after CD19 CAR T cell treatment.
* In phase I age \>18 years, in phase II all ages
* Measurable disease per Lugano classification.
* Performance status ECOG 0-2.
* Adequate bone marrow function as evidenced by:

  * Absolute neutrophil count (ANC) ≥ 1x10\^9/l/L
  * Platelet ≥ 50x 10\^9/l
  * Absolute lymphocyte count ≥ 0,1x10\^9/L
* Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:

  * Creatinine clearance (Cockcroft Gault) ≥ 30 mL/min
  * Serum Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 Upper limit of normal (ULN) and S-Bilirubin \<1.5x UNL
  * Cardiac ejection fraction ≥ 40%
* Functional venous for administration of IMP.
* Fertile individuals must consent to use contraceptives during participation in the trial.

Exclusion Criteria:

* Other CD20-positive lymphomas i.e Burkitt lymphoma, primary CNS lymphoma, plasmablastic lymphoma or CLL transformed to DLBCL/HGBL (Richter transformation)
* Any significant medical or psychiatric illness that would prevent the subject from giving informed consent or from following the study procedures.
* Known human immunodeficiency virus (HIV) infection.
* Impending organ-compromising disease.
* Rapidly progressing disease
* Active and/or severe infection (e.g., tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
* Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the subject to perform the treatment.
* Treatment with an investigational product within 30 days prior to enrolment
* Potential sign of hypersensitivity reaction to tocilizumab or any of the agents used in this study
* Systemic corticosteroid treatment (\>10mg/day) \<5 days prior to IMP treatment or \<7 days prior leukapheresis.
* Pregnancy

主要终点：Incidence of dose limiting toxicity · The incidence of dose limiting toxicity (DLT). Number of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs) · First infusion up to 30 days；Adverse events · The nature, frequency, severity, and tolerability of adverse events (AEs) including clinically significant laboratory data, and their relation to dosage. · 24 months；Pharmacodynamic (PD) and pharmacokinetic (PK) · PD is assessed by determine circulating B cell level; PK is assessed by determine circulating CAR20(NAP)-T cells. · Either 24 month or 15 years during long-term follow up if clinically indicated
次要终点：Objective response rate [ORR]；Progression free survival [PFS]；Best Objective Response；Duration of Response (DOR)；Overall Survival (OS)

• Treatment · EXPERIMENTAL · CAR20(NAP)-T treatment

The purpose is to study the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of CAR20(NAP)-T for patients with B-cell malignancies.