MB-CART20.1 Lymphoma

Miltenyi Biotec

Status and phase: Completed; Phase 2; Phase 1

Conditions: Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; B-cell Lymphoma Recurrent; B-cell Lymphoma Refractory

Treatments: Biological: MB-CART20.1

Study type: Interventional

Funder types: Industry

Identifiers

NCT03664635

M-2016-312

Details and patient eligibility

About

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.

Full 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)

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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10 participants in 4 patient groups

Phase I - Safety Dose Level

Experimental group

Description:

In phase I three (3) + 3 patients will be treated with 1x10\^5 MB-CART20.1 cells per kg body weight administered intravenously as single dose in the preceding safety dose level

Treatment:

Biological: MB-CART20.1

Phase I - Dose Level 1

Experimental group

Description:

In phase I six (6) + 3 patients will be treated with 1x10\^6 MB-CART20.1 cells per kg body weight administered intravenously as single dose in the dose level 1

Treatment:

Biological: MB-CART20.1

Phase I - Dose Level 2

Experimental group

Description:

In phase I six (6) + 3 patients will be treated with 3x10\^6 MB-CART20.1 cells per kg body weight administered intravenously as single dose in the dose level 2

Treatment:

Biological: MB-CART20.1

Phase II

Experimental group

Description:

The number of additional patients who will be treated with MB-CART20.1 cells in Phase II is depending on the number of evaluable patients treated with the maximum tolerated dose (MTD) level and the results in Part I

Treatment:

Biological: MB-CART20.1