A Phase I/II Safety, Dose Finding and Feasibility Trial of MB-CART20.1 in Patients with Relapsed or Resistant CD20 Positive B-NHL
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Phase I - Determination of the maximum tolerated dose (MTD)
研究概览
简要总结
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.
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: MB-CART20.1 (Biological)
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
干预措施: MB-CART20.1 (Biological)
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
干预措施: MB-CART20.1 (Biological)
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
干预措施: MB-CART20.1 (Biological)
结局指标
主要结局
Phase I - Determination of the maximum tolerated dose (MTD)
时间窗: 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
时间窗: 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.
次要结局
- Phase II - Best overall response rate over 1 year(1 year after infusion of MB-CART20.1)
- Phase I - Best overall response rate over 4 weeks and 3 months(4 weeks and 3 months after infusion of MB-CART20.1)
- Phase I - Occurrence of B-cell aplasia(1 year after infusion of MB-CART20.1)
- Phase I - Phenotype and Persistence of MB-CART20.1(1 year after infusion of MB-CART20.1)
- Phase II - Overall response rate over 4 weeks and 3 months(4 weeks and 3 months after infusion of MB-CART20.1)
- Phase II - Occurrence of B-cell aplasia(1 year after infusion of MB-CART20.1)
- Phase I - Related safety and toxicity of MB-CART20.1(months 3, 6, 9 and 12 after infusion of MB-CART20.1)
- Phase I - Best overall response rate over 1 year(1 year after infusion of MB-CART20.1)
- Phase II - Overall response rate over 1 year(1 year after infusion of MB-CART20.1)
- Phase II - Number of patients with CR, PR, SD and PD(1 year after infusion of MB-CART20.1)
- Phase II -Percentage of patients with CR, PR, SD and PD(1 year after infusion of MB-CART20.1)
- Phase II - Safety and toxicity assessment of MB-CART20.1(1 year after infusion of MB-CART20.1)
- Phase II - Phenotype and Persistence of MB-CART20.1(1 year after infusion of MB-CART20.1)