A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of BCMA-targeted LCAR-BCDR Cells Product in Patients With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 9
- 主要终点
- Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is a prospective, single-arm, open-label, dose-finding and dose-expansion study that evaluates the safety, tolerability, PK, and anti-tumor efficacy of LCAR-BCDR cell preparations in relapsed/refractory multiple myeloma subjects who received adequate standard therapy.
详细描述
The research plan stipulates that "four dose groups will be conducted, namely 30×10^6, 100×10^6, 200×10^6, and 400×10^6". The research team held a SET meeting and decided to increase the dose escalation to 600×10^6 and 800×10^6, and obtained ethical approval from all sites.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject voluntarily participates in the clinical study; Fully understand and be Informed of the study and sign the Informed consent (Informed Consent Form, ICF); Willing to follow and able to complete all test procedures; Informed consent must be obtained before initiating any tests or procedures related to the study that are not part of the standard treatment of the subject's disease;
- •Subjects ≥ 18 years of age.
- •Documented initial diagnosis of MM according to IMWG diagnostic criteria.
- •Presence of measurable disease at screening.
- •Received a PI and an IMiD (except thalidomide).
- •Received at least 3 prior lines of therapy for multiple myeloma, undergone at least 1 complete cycle of treatment for each line, unless progressive disease (PD) was documented by IMWG criteria as the best response to the regimen. Also, subjects refractory or intolerant to any PI and any IMiD in their previous treatment afterwards are eligible.
- •Expected survival ≥ 3 months.
- •Clinical laboratory values meet screening visit criteria
- •Fertile women must be negative using a highly sensitive serum pregnancy test (β human chorionic gonadotropin [β -HCG]) at screening time and before initial treatment with cyclophosphamide and fludarabine;
排除标准
- •No response to prior BCMA-targeted CAR-T therapy (except in subjects who relapsed after CR to prior CAR-T treatment).
- •Prior treatment with any antibody targeting BCMA.
- •Diagnosed or pretreated for an invasive malignancy other than multiple myeloma.
- •Prior anti-tumor treatment (before pretreatment) with insufficient washout period.
- •Known active, or prior history of central nervous system (CNS) involvement, or clinical signs of membrane/spinal membrane involvement of multiple myeloma.
- •Positive of any hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), human immunodeficiency virus antibody (HIV-Ab) at the time of screening.
- •Serious underlying medical conditions
- •Male subjects who have a birth plan during the study period or within 1 year after the study treatment.
- •Female subjects who are pregnant, breast-feeding, or plan to become pregnant during the study period or within 1 year after the study treatment.
- •The investigator considered that the subjects were not suitable for any conditions of participation in the study.
研究组 & 干预措施
LCAR-BCDR cells product
Each subject will receive LCAR-BCDR cells
干预措施: LCAR-BCDR cells product (Biological)
结局指标
主要结局
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
时间窗: Minimum 2 years after LCAR-BCDR infusion (Day 1)
An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment.
Recommended Phase 2 dose (RP2D) finding
时间窗: 30 days after LCAR-BCDR infusion (Day 1)
RP2D established through ATD+BOIN design
CAR positive T cells in peripheral blood and bone marrow
时间窗: Minimum 2 years after LCAR-BCDR infusion (Day 1)
CAR positive T cells in peripheral blood and bone marrow after LCAR-BCDR infusion
CAR transgene levels in peripheral blood and bone marrow
时间窗: Minimum 2 years after LCAR-BCDR infusion (Day 1)
CAR transgene levels in peripheral blood and bone marrow after LCAR-BCDR infusion
次要结局
- Overall Response Rate (ORR)(Minimum 2 years after LCAR-BCDR infusion (Day 1))
- Overall Survival (OS)(Minimum 2 years after LCAR-BCDR infusion (Day 1))
- Progression-free survival (PFS)(Minimum 2 years after LCAR-BCDR infusion (Day 1))
- Incidence of anti-LCAR-BCDR antibody(Minimum 2 years after LCAR-BCDR infusion (Day 1))
研究者
Weijun Fu
Shanghai Changzheng Hospital
Shanghai Changzheng Hospital