MB-CART20.1 Lymphoma
- Conditions
- B-cell Lymphoma RecurrentNon-Hodgkin's LymphomaRelapsed or Refractory B-cell Non-Hodgkin's LymphomaB-cell Lymphoma Refractory
- Interventions
- Registration Number
- NCT03664635
- Lead Sponsor
- Miltenyi Biomedicine GmbH
- 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)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 10
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase I - Dose Level 1 MB-CART20.1 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 Phase I - Dose Level 2 MB-CART20.1 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 Phase I - Safety Dose Level MB-CART20.1 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 Phase II MB-CART20.1 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
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 - 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 - 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 - 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 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 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 - 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.
Trial Locations
- Locations (2)
Universitätsklikum Leipzig, AöR
🇩🇪Leipzig, Germany
University Hospital of Cologne - Clinic for Internal Medicine I
🇩🇪Cologne, Germany