NCT03464916已完成1 期
A Phase 1, Open-Label, Dose-Escalation, Pharmacokinetic, and Pharmacodynamic Study of the Safety and Efficacy of CAR2 Anti-CD38 A2 CAR-T Cells in Patients With Relapsed or Refractory Multiple Myeloma
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 7
- 主要终点
- Determine the MTD
研究概览
简要总结
The study is an open-label Phase 1 single dose-escalation safety study of CAR2 Anti-CD38 A2 CAR-T Cells in patients with Relapsed or Refractory Multiple Myeloma, who meet all other eligibility criteria.
详细描述
All subjects who received investigational CAR-T therapy will be included in the analyses and summaries of safety, efficacy, pharmacokinetic, and pharmacodynamic assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •The patient must either have relapsed refractory multiple myeloma (RRMM) after receiving prior lines of anti-myeloma treatments that included at least lenalidomide (Revlimid®), pomalidomide (Pomalyst®), bortezomib (Velcade®), carfilzomib (Kyprolis®), and daratumumab (Darzalex®) (refractory MM is defined as the development of disease progression during therapy with an anti-myeloma regimen or within 60 days of the last dose of an anti-myeloma regimen or the achievement of less than a partial response (PR) after greater than or equal to 2 cycles; for relapsing patients the duration from the last dose of the last prior treatment regimen to relapse must be less than or equal to 12 months); OR have multiple myeloma that is refractory to or has relapsed within 1 year of receiving high-dose therapy [HDT]/autologous stem cell transplantation [ASCT] in first- or second-line (refractory is defined as the achievement of less than a PR at the Day 90 to 100 post-ASCT response assessment)
- •Must have measurable disease as defined by the following: Serum M-protein greater than or equal to 1 g/dL; OR Urine M-protein greater than or equal to 200 mg/24 hours; OR Serum free light chain (FLC) assay; involved FLC level greater than or equal to 10 mg/dL provided the serum FLC ratio is abnormal; OR greater than or equal to 30% clonal plasma cells in the bone marrow aspirate or biopsy sample
- •Must have a life expectancy of at least 12 weeks
- •Subjects should be willing and able to comply with the study schedule and protocols
- •Females of childbearing potential must have 2 negative pregnancy tests, agree to ongoing pregnancy testing during the study, and sexually active female and male subjects must be willing to use an effective method to avoid pregnancies.
排除标准
- •Subjects who received anticancer therapy or investigational drug within 28 days of first dose
- •Subjects who received any approved anticancer chemotherapy within 21 days of first dose (exception cyclophosphamide as NMA conditioning)
- •Subjects with unresolved toxicity greater than Grade 2 from previous therapies
- •Have myeloma involvement of central nervous system (CNS) or a history of brain metastasis or spinal cord compression
- •Subjects with an ECOG performance status greater than or equal to 3
- •Has received allogenic hematopoietic stem cell transplantation (HSCT) within 6 months, have active graft-versus-host disease (GVHD) following transplant, or receiving immunosuppressive therapy following a transplant
- •Has received any CAR cell line therapies
- •Has any clinically significant low baseline lab results for hemoglobin, platelet counts, and neutrophil counts, at screening unless resulting from underlying RRMM.
- •Has any clinically significant elevated baseline lab results for serum creatinine, AST, and total bilirubin (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome) at screening regardless of causality.
- •Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.
- •Female subjects who are pregnant or breastfeeding
- •Active bacterial, viral or fungal infections
- •Has active plasma cell leukemia
- •Has medical condition, abnormality, or psychiatric illness that would prevent study participation
- •Left ventricular ejection fraction (LVEF) less than 40%
结局指标
主要结局
Determine the MTD
时间窗: 28 days
The MTD is assessed according to a 3+3 dose-escalation design by the occurrence of treatment-emergent dose-limiting toxicities during the 28-day Treatment Period in the dose-escalation phase of the study
次要结局
- Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the Cmax(28 days)
- Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the AUC(28 days)
- The determination of the recommended phase 2 dose will be based on an evaluation of overall response rate.(6 months)
- The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of overall survival.(6 months)
- Evaluate the safety of Anti-CD38 A2 CAR-T cells in Patients with RRMM by incidence of treatment-emergent adverse events(6 months)
- Assess preliminary efficacy by response rate in accordance with the modified International Myeloma Working Group (IMWG) criteria(6 months)
- Assess preliminary efficacy by overall survival.(6 months)
- The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of duration of response.(6 months)
- Assess preliminary efficacy by duration of response in accordance with the modified International Myeloma Working Group (IMWG) criteria.(6 months)
- The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of treatment-emergent events.(6 months)
- The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of depth of response.(6 months)
- Assess preliminary efficacy by depth of response in accordance with the modified International Myeloma Working Group (IMWG) criteria.(6 months)
- Assess preliminary efficacy by progression-free survival.(6 months)
- The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of progression-free survival.(6 months)
研究者
研究点 (7)
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