Practical Clinical Study of Dual-targeting BCMA-CD19 CAR-T Cell Therapy for Extramedullary Infiltration in Refractory/Relapsed Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
This is a multicenter, open-label, non-randomized, single-arm clinical trial. Patients with relapsed/refractory multiple myeloma accompanied by extramedullary infiltration will receive BCMA - CD19 CAR-T cell therapy.
The primary objective is to prospectively evaluate the safety of dual-targeting BCMA and CD19 CAR - T cell therapy for extramedullary infiltration in relapsed/refractory multiple myeloma. The primary endpoints are to assess the type and incidence of dose-limiting toxicity (DLT) within one month after the infusion of BCMA-CD19 CAR-T cells in patients, as well as the incidence and severity of adverse events within one month after the infusion. It is expected that no more than 18 participants will be recruited.
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
- •Voluntarily participate in the trial and have good compliance.
- •Aged between 18 and 75 years old, regardless of gender.
- •Diagnosed with relapsed or refractory multiple myeloma according to the criteria of the International Myeloma Working Group (IMWG)2, and have measurable extramedullary lesions due to multiple myeloma.
- •Positive for BCMA in flow cytometry of bone marrow or cerebrospinal fluid tumor cells or immunohistochemistry of tumor tissue.
- •Organ functions: ① Cardiac function: Left ventricular ejection fraction > 50% (by echocardiogram) in the past 2 weeks. ② Liver function: Alanine aminotransferase and aspartate aminotransferase < 3 times the upper limit of normal (ULN). ③ Renal function: Creatinine clearance rate ≥ 40 mL/min (by Cockcroft and Gault formula). ④ Coagulation function: PT and APPT < 1.5 times the ULN. ⑤ Arterial oxygen saturation (SpO₂) > 95%. ⑥ Pulmonary function: FEV₁% predicted value ≥ 50%.
- •Female patients of childbearing age must have a negative serum pregnancy test at screening and before receiving cyclophosphamide and fludarabine or melphalan treatment; male patients should be willing to use effective contraceptive methods for 1 year after receiving the study treatment.
- •ECOG score ≤
- •Expected survival time > 3 months.
排除标准
- •Pregnant or lactating women.
- •Active infections that have not been effectively controlled.
- •Active autoimmune diseases that have not been effectively controlled.
- •Adverse reactions caused by previous treatments have not recovered to CTCAE grade ≤
- •For allogeneic transplant patients, active graft - versus - host disease (GVHD) that has not been effectively controlled.
- •Presence of any of the following: HBV - DNA copy number above the lower limit of detection; positive hepatitis C antibody (HCV - Ab) with HCV - RNA copy number above the lower limit of measurability; positive anti - Treponema pallidum antibody (TP - Ab); positive human immunodeficiency virus (HIV) antibody test.
- •Allergic or intolerant to fludarabine or cyclophosphamide.
- •Suffering from known symptomatic non - plasma cell infiltrative central nervous system diseases.
- •Uncontrollable cardiovascular and cerebrovascular diseases within 6 months, such as: a. New York Heart Association (NYHA) class III or IV congestive heart failure. b. Myocardial infarction occurred or coronary artery bypass grafting (CABG) was received ≤ 6 months before enrollment. c. Clinically significant ventricular arrhythmia or a history of unexplained syncope (excluding cases caused by vasovagal or dehydration). d. A history of severe non - ischemic cardiomyopathy.
- •A history of other untreated malignancies within the past 5 years or having other untreated malignancies concurrently.
- •The investigator assesses that the subject cannot or is unwilling to comply with the requirements of the study protocol.
- •Previous use of a CAR - T vector with the same structure.
研究组 & 干预措施
Dual-targeting BCMA-CD19 CAR-T cell therapy
Patients receive dual-targeting BCMA-CD19 CAR-T cell therapy
干预措施: Dual-targeting BCMA-CD19 CAR-T cell infusion (Drug)
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: 30 days
Incidence and type of dose-limiting toxicity(DLT) within 1 month of BCMA-CD19 CAR-T infusion.
Adverse events (AEs）
时间窗: 30 days
Total number, incidence and severity of adverse events (AEs) within 30 days of BCMA-CD19 CAR-T infusion
次要结局
- Overall remission rate (ORR)(90 days)
- Event Free Survival (EFS)(from enrollment to the end of treatment at 2 years)
- Duration of Response (DOR)(from enrollment to the end of treatment at 2 years)
- Overall Survival (OS)(from enrollment to the end of treatment at 2 years)
研究者
Jing Pan
Director of the department of Immunotherapy for Hematopoietic Malignancies
Beijing GoBroad Hospital