Clinical trial NCT03664635: MB-CART20.1 Lymphoma
Official title: A Phase I/II Safety, Dose Finding and Feasibility Trial of MB-CART20.1 in Patients with Relapsed or Resistant CD20 Positive B-NHL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Non-Hodgkin's Lymphoma
B-cell Lymphoma Refractory
B-cell Lymphoma Recurrent
Lead sponsor: Miltenyi Biomedicine GmbH
Sponsor class: INDUSTRY
First posted: 2018-09-10
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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)

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

Primary outcomes:
measure: Phase I - Determination of the maximum tolerated dose (MTD)
timeFrame: until day 28 after infusion of MB-CART20.1
measure: Phase II - Best overall response rate
timeFrame: 3 months after infusion of MB-CART20.1
Secondary outcomes:
measure: Phase I - Related safety and toxicity of MB-CART20.1
timeFrame: months 3, 6, 9 and 12 after infusion of MB-CART20.1
measure: Phase I - Best overall response rate over 4 weeks and 3 months
timeFrame: 4 weeks and 3 months after infusion of MB-CART20.1
measure: Phase I - Best overall response rate over 1 year
timeFrame: 1 year after infusion of MB-CART20.1
measure: Phase I - Occurrence of B-cell aplasia
timeFrame: 1 year after infusion of MB-CART20.1
measure: Phase I - Phenotype and Persistence of MB-CART20.1
timeFrame: 1 year after infusion of MB-CART20.1
measure: Phase II - Best overall response rate over 1 year
timeFrame: 1 year after infusion of MB-CART20.1
measure: Phase II - Overall response rate over 4 weeks and 3 months
timeFrame: 4 weeks and 3 months after infusion of MB-CART20.1
measure: Phase II - Overall response rate over 1 year
timeFrame: 1 year after infusion of MB-CART20.1
measure: Phase II - Number of patients with CR, PR, SD and PD
timeFrame: 1 year after infusion of MB-CART20.1
measure: Phase II -Percentage of patients with CR, PR, SD and PD
timeFrame: 1 year after infusion of MB-CART20.1
measure: Phase II - Safety and toxicity assessment of MB-CART20.1
timeFrame: 1 year after infusion of MB-CART20.1
measure: Phase II - Occurrence of B-cell aplasia
timeFrame: 1 year after infusion of MB-CART20.1
measure: Phase II - Phenotype and Persistence of MB-CART20.1
timeFrame: 1 year after infusion of MB-CART20.1
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: University Hospital of Cologne - Clinic for Internal Medicine I
city: Leipzig
country: Germany
facility: Universitätsklikum Leipzig, AöR
Study officials:
affiliation: Universitätsklinikum Köln
name: Peter Borchmann, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: