CAR20(NAP)-T Therapy for B Cell Lymphoma (CARMA-01 Study)

Prior treatment

• Treatment with an investigational product within 30 days prior to enrolment
• Systemic corticosteroid treatment (\>10mg/day) \<5 days prior to IMP treatment or \<7 days prior leukapheresis.

Other illness

• 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.
• Potential sign of hypersensitivity reaction to tocilizumab or any of the agents used in this study

Other

• Other CD20-positive lymphomas i.e Burkitt lymphoma, primary CNS lymphoma, plasmablastic lymphoma or CLL transformed to DLBCL/HGBL (Richter transformation)
• Pregnancy

• 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.