MB-CART20.1 Lymphoma

This trial is a phase I/II trial to assess safety, dose finding and feasibility of ex vivo generated MB-CART20.1 cells in patients with relapsed or refractory CD20 positive B-NHL.

MB-CART20.1 consists of autologous Anti-CD20 Chimeric Antigen Receptor (CAR) transduced CD4 /CD8 enriched T cells targeting CD20-positive tumor cells in Non-Hodgkin-Lymphoma (NHL)

Eligibility Criteria:
Inclusion Criteria:

* Refractory/relapsed CD20+ B-NHL (including malignant transformation like Richter's transformation) with no curative treatment option.
* At least 18 years of age
* Estimated life expectancy of more than 3 months
* ECOG performance status (Eastern cooperative oncology group) of 0-2
* Negative serological HBV (Hepatitis B virus) test, negative testing of HCVAb (Hepatitis C virus Antibody), negative HIV1/2 (Human immunodeficiency virus 1/2 ) test within 6 weeks prior to enrollment
* No childbearing potential or negative pregnancy test at screening and before chemotherapy in women with childbearing potential.
* Signed and dated informed consent before conduct of any trial-specific procedure

Exclusion Criteria:

* Participation in another interventional trial that could interact with this trial
* Any evidence 0f CNS (Central nervous system) involvement
* Known history or presence of clinically relevant CNS pathology
* Patients with history of primary immunodeficiency,
* Patients with any history of auto-immune induced condition such as those caused by checkpoint inhibitors, MEK inhibitors or BRAF inhibitors, for example pituitary hypophysitis must be excluded
* Patients with Chronic Lymphocytic Leukemia unless suffering from malignant transformation
* Active systemic fungal, viral or bacterial infection
* Serious cardiac functional incapacity (class III or IV as defined by the New York Heart Association Classification)
* Severe pulmonary disease (DLCO (Transfer factor of the lung for carbon monoxide) and/or FEV1 (Forced expiratory volume in 1 second) \< 65%, dyspnea at rest)
* Liver dysfunction as indicated by a total bilirubin, AST (Aspartate Aminotransferase), and ALT (Alanine aminotransferase) ≥ 2 the institutional ULN (Upper limit of normal) value, unless directly attributable to the patient's tumor
* Creatinine clearance \<50 ml/min calculated according to the modified formula of Cockcroft and Gault
* Pregnant or lactating women
* Active secondary malignancy requiring treatment (except basal cell carcinoma or malignant tumor curatively treated by surgery) within the last 5 years before enrollment.
* Medical condition requiring prolonged use of systemic corticosteroids (\> 1 month)
* Prior therapy with genetically modified substances
* Use of anti-CD20 antibodies within 4 weeks before leukapheresis
* Chemotherapy within 4 weeks prior to leukapheresis
* Other treatment within 4 weeks or two half-lives, whichever is longer before MB-CART20.1 infusion. This pertains to immunomodulatory therapies such as checkpoint inhibitors because of the influence on the immune system
* Concurrent systemic radiotherapy
* Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation e.g. as part of the mandatory lymphodepletion protocol, pre-medication for infusion, rescue medication/salvage therapies for treatment of related toxicities
* Patients in which such medication is contraindicated for other reasons than hypersensitivity (e.g. live vaccines and fludarabine)
* Patients in which trial related procedures are contraindicated as judged by the investigator, e.g. lumbar punctures for CSF (Cerebrospinal fluid) sampling
* Patient's lack of accountability, inability to appreciate the nature, meaning and consequence of the trial and to formulate his/her own wishes correspondingly
* Patients who have a relationship of dependence or employer employee relationship to the sponsor or the investigator
* Committal to an institution on judicial or official order
* Cerebral dysfunction, legal incapacity
* Other investigational treatment within 4 weeks before IMP (Investigational Medicinal Product) infusion
* Clinically relevant autoimmune diseases or history of autoimmune disease