A Phase II Study of CART Cell (MB-CART19.1) in Patients With Relapsed or Refractory CD19 Positive NHL
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- overall response rate
研究概览
简要总结
This is a Prospective Single Center, open label, Non-randomized, Single Arm, Single Dose, Phase II Clinical Trial. Adult patients >18-year-old with CD19+ Non-Hodgkin lymphoma are eligible for the study if they meet eligibility criteria. Patients will receive a fresh single dose of MB-CART-19.1 and will be followed for 12 months and evaluated for efficacy and safety.
详细描述
This is a prospective single center, open label, non-randomized, single arm, single dose, optimal 2-stage Simon design, and Phase II clinical trial. The trial includes Adult patients > 18-year-old and up to 75 years old, with CD19+ non-Hodgkin lymphoma including diffuse Large B-cell Lymphoma, primary mediastinal B-cell lymphoma and relapsed refractory follicular lymphoma.
Single infusion of freshly prepared MB-CART19.1 cells manufactured according to Miltinyi Biotec product manufacturing guidelines and good manufacturing product (GMP) of KHCC manufacturing standard operating procedures (SOPs).
The patients will receive one infusion of the MB-CART19.1 product in infusion solution at a final volume adapted to the patients' weight, over a time of approx. 5-20 minutes (intravenous infusion via a large peripheral vein or central line).
The objective of this trial is to assess the efficacy and safety of ex vivo generated MB-CART19.1 in adult patients with relapsed or refractory CD19 positive Non-Hodgkin lymphoma including diffuse Large B-cell Lymphoma, primary mediastinal B-cell lymphoma and relapsed refractory follicular lymphoma
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligible patients with a diagnosis of aggressive NHL:
- •Patients after progression on at least one standard chemotherapy and one salvage regimen or
- •Patients considered for alloSCT but are found ineligible or
- •Patients who have relapsed post alloSCT at least 100 days post-transplant, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
- •Patients with CNS disease (excluding isolated CNS lymphoma) are eligible only if disease has been successfully cleared at the time of inclusion.
- •CD19 expression must be detected on the malignant cells by flow cytometry or immunohistochemistry
- •Age > 18 year up to 75 years old (if deemed fit by treating investigator);
- •Baseline absolute CD3+ T cell count by FACS ≥100/µl;
- •ECOG performance score of 0-2 at screening;
- •No active Hepatitis B, Hepatitis C, HIV I/II
- •No childbearing potential or negative pregnancy test at screening within 7 days from starting lymphodepletion chemotherapy and before bridging chemotherapy in women with childbearing potential;
- •Signed and dated informed consent, before conduct of any trial-specific procedure.
排除标准
- •Residual CNS disease
- •Current autoimmune disease, or history of autoimmune disease with potential CNS involvement;
- •Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis)
- •History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease free for ≥3 years;
- •Pulmonary function: Patients with pre-existing severe lung disease or DLCO of less than 50% or active pulmonary infiltrates on imaging studies.
- •Cardiac function: left ventricular ejection faction <50% by echocardiogram,
- •Renal function: Creatinine clearance <50 mL/min/1.73 m2, by Cockcroft-Gault formula (Cockcroft and Gault 1976) for patients ≥18 years.
- •Liver function: patients with serum bilirubin ≥3 times upper limit of or AST or ALT > 5 times upper limit of normal, unless due to lymphoma liver infiltration in the estimation of the investigator.
- •Rapidly progressive disease that in the estimation of the investigator would compromise ability to complete study therapy;
- •Pregnant or breast-feeding females
- •Medications: systemic chemotherapies, corticosteroids with the exception of physiologic replacement dosing, Fludarabine/clofarabine or immunosuppressive (Calcineurin inhibitors) drugs and antibodies or investigational drugs or donor lymphocyte transfusions or radiation therapy within 30 days prior to apheresis, and rituximab within 2 weeks with the exception of Intrathecal chemotherapy is allowed prior to treatment, but should be discontinued 10 days prior to-CART19 infusion to limit the risk of neurotoxicities;
- •Patients of child-bearing or fathering potential not willing to practice an effective form of birth control from the time of enrollment and for three months after dosing of the CARTs;
- •Concurrent participation in another interventional trial that could interact with this trial, e.g. CAR T trials.
- •Other investigational treatment within 4 weeks before CARTs infusion;
- •Cerebral dysfunction, legal incapacity of adult patients;
- •Committal to an institution on judicial or official order.
结局指标
主要结局
overall response rate
时间窗: on week 4 and at month 3 in patients not achieving CR on week 4
ORR in NHL patients defined as the rate of overall response (CR or PR)
次要结局
- Safety and toxicity(From enrolment to the end of follow up at one year)
- CRS(From enrolment to the end of follow up at one year)
- Disease-free survival(at 1 year after receiving study treatment)
- Duration of response(From enrolment to end of follow up at one year)
- ICANS(From enrolment to the end of follow up at one year)
- relapse rate(From enrolment to the end of follow up at one year)
- time to relapse(From enrolment to the end of follow up at one year)
- overall survival(at 1 year after receiving study treatment)