Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, B-cell Lymphoma Refractory, B-cell Lymphoma Recurrent
Conditions
Brief summary
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.
Detailed description
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)
Interventions
BIOLOGICALMB-CART20.1
MB-CART20.1 consists of autologous CD20 Chimeric Antigen Receptor (CAR) transduced CD4 /CD8 enriched T cells targeting CD20-positive tumor cells in NHL
Sponsors
Miltenyi Biomedicine GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I - Determination of the maximum tolerated dose (MTD) | until day 28 after infusion of MB-CART20.1 | MTD is defined as the highest dose level at which \< 33% of patients experience Dose Limiting Toxicity (DLT). Safety and toxicity assessment of MB-CART20.1 per adverse events (AE) reporting classified according to CTCAE version 5.0. |
| Phase II - Best overall response rate | 3 months after infusion of MB-CART20.1 | Response (Complete response (CR), Partial response (PR), Stable disease (SD), Progressive disease (PD)) is defined according to Cheson criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase I - Best overall response rate over 1 year | 1 year after infusion of MB-CART20.1 | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
| Phase I - Occurrence of B-cell aplasia | 1 year after infusion of MB-CART20.1 | Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry. |
| Phase I - Phenotype and Persistence of MB-CART20.1 | 1 year after infusion of MB-CART20.1 | Blood samples for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed. |
| Phase II - Best overall response rate over 1 year | 1 year after infusion of MB-CART20.1 | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
| Phase II - Overall response rate over 4 weeks and 3 months | 4 weeks and 3 months after infusion of MB-CART20.1 | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
| Phase I - Related safety and toxicity of MB-CART20.1 | months 3, 6, 9 and 12 after infusion of MB-CART20.1 | Per adverse events (AE) reporting classified according to CTCAE version 5.0. |
| Phase II - Number of patients with CR, PR, SD and PD | 1 year after infusion of MB-CART20.1 | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
| Phase II -Percentage of patients with CR, PR, SD and PD | 1 year after infusion of MB-CART20.1 | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
| Phase II - Safety and toxicity assessment of MB-CART20.1 | 1 year after infusion of MB-CART20.1 | Per adverse events (AE) reporting classified according to CTCAE version 5.0. |
| Phase II - Occurrence of B-cell aplasia | 1 year after infusion of MB-CART20.1 | Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry. |
| Phase II - Phenotype and Persistence of MB-CART20.1 | 1 year after infusion of MB-CART20.1 | Blood samples for determination of persistence/phenotyping of infused MB-CART20.1 will be analysed. |
| Phase II - Overall response rate over 1 year | 1 year after infusion of MB-CART20.1 | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
| Phase I - Best overall response rate over 4 weeks and 3 months | 4 weeks and 3 months after infusion of MB-CART20.1 | Response (CR, PR, SD and PD) is defined according to Cheson criteria. |
Countries
Germany
Outcome results
None listed