MB-CART20.1 Lymphoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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)
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase I - Safety Dose Level 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 |
Biological: MB-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
Other Names:
|
| Experimental: Phase I - Dose Level 1 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 |
Biological: MB-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
Other Names:
|
| Experimental: Phase I - Dose Level 2 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 |
Biological: MB-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
Other Names:
|
| Experimental: Phase II 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 |
Biological: MB-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
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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.
- 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 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 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Refractory/relapsed CD20+ B-NHL (including malignant transformation like Richter's transformation) with no curative treatment option.
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At least 18 years of age
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Estimated life expectancy of more than 3 months
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ECOG performance status (Eastern cooperative oncology group) of 0-2
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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
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No childbearing potential or negative pregnancy test at screening and before chemotherapy in women with childbearing potential.
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Signed and dated informed consent before conduct of any trial-specific procedure
Exclusion Criteria:
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Participation in another interventional trial that could interact with this trial
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Any evidence 0f CNS (Central nervous system) involvement
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Known history or presence of clinically relevant CNS pathology
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Patients with history of primary immunodeficiency,
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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
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Patients with Chronic Lymphocytic Leukemia unless suffering from malignant transformation
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Active systemic fungal, viral or bacterial infection
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Serious cardiac functional incapacity (class III or IV as defined by the New York Heart Association Classification)
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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)
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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
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Creatinine clearance <50 ml/min calculated according to the modified formula of Cockcroft and Gault
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Pregnant or lactating women
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Active secondary malignancy requiring treatment (except basal cell carcinoma or malignant tumor curatively treated by surgery) within the last 5 years before enrollment.
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Medical condition requiring prolonged use of systemic corticosteroids (> 1 month)
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Prior therapy with genetically modified substances
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Use of anti-CD20 antibodies within 4 weeks before leukapheresis
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Chemotherapy within 4 weeks prior to leukapheresis
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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
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Concurrent systemic radiotherapy
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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
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Patients in which such medication is contraindicated for other reasons than hypersensitivity (e.g. live vaccines and fludarabine)
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Patients in which trial related procedures are contraindicated as judged by the investigator, e.g. lumbar punctures for CSF (Cerebrospinal fluid) sampling
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Patient's lack of accountability, inability to appreciate the nature, meaning and consequence of the trial and to formulate his/her own wishes correspondingly
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Patients who have a relationship of dependence or employer employee relationship to the sponsor or the investigator
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Committal to an institution on judicial or official order
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Cerebral dysfunction, legal incapacity
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Other investigational treatment within 4 weeks before IMP (Investigational Medicinal Product) infusion
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Clinically relevant autoimmune diseases or history of autoimmune disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital of Cologne - Clinic for Internal Medicine I | Cologne | Germany | 50937 | |
| 2 | Universitätsklikum Leipzig, AöR | Leipzig | Germany |
Sponsors and Collaborators
- Miltenyi Biomedicine GmbH
Investigators
- Principal Investigator: Peter Borchmann, Prof. Dr., Universitätsklinikum Köln
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- M-2016-312