Clinical Trial for the Safety and Efficacy of CD19/BCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
A Study of CD19/BCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma.
详细描述
This is a double-arm, single-center study. This study is indicated for relapsed and/or refractory B-cell acute lymphoblastic leukemia, B-cell non-Hodgkin's lymphoma and multiple myeloma, the selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 120 patients will be enrolled for this trial. Primary objective is to explore the safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of CD19+ ALL, CD19+ NHL, or BCMA+ MM per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2020.v2);
- •Relapsed or refractory B cell hematological malignancies (meeting one of the following conditions):
- •CR not achieved after standardized chemotherapy;
- •CR achieved following the first induction, but CR duration is less than 12 months;
- •Ineffectively after first or multiple remedial treatments;
- •2 or more relapses;
- •Relapse after hematopoietic stem cell transplantation;
- •Extramedullary leisions which were ineffective to radiotherapy or chemotherapy;
- •Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
- •Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
- •No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
- •Estimated survival time ≥ 12 weeks;
- •ECOG performance status 0 to 2;
- •Women of childbearing age had negative pregnancy test during screening period and before administration, and agreed to take effective contraceptive measures at least one year after infusion.
- •Patients volunteer to participate in the study and sign the informed consent.
排除标准
- •Subjects with any of the following exclusion criteria were not eligible for this trial:
- •History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
- •Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
- •Pregnant (or lactating) women;
- •Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
- •Active infection of hepatitis B virus or hepatitis C virus;
- •Concurrent therapy with systemic steroids within 2 weeks prior toscreening, except for the patients recently or currently receiving in haledsteroids;
- •Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
- •Creatinine >2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin >2.0 mg/dl;
- •Other uncontrolled diseases that were not suitable for this trial;
- •Patients with HIV infection;
- •Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.
研究组 & 干预措施
Administration of CD19/BCMA Targeted CAR T-cells and dasatinib
Dose levels of CAR-T cells are based on clinical trials of similar foreign products. Meanwhile, dasatinib would be combined as the following regimens: 1) Dasatinib preconditioning CAR-T cells during the manufacturing; 2) Dasatinib for the intervention of cytokine release storm after CAR-T cell infusion; 3) Dasatinib for the intervention of neurotoxicities after CAR-T cell infusion; 4) Dasatinib for the phase of CAR-T cell decreasing.
干预措施: CD19/BCMA Targeted CAR T-cells and dasatinib (Drug)
Administration of CD19/BCMA Targeted CAR T-cells
Dose levels of CAR-T cells are based on clinical trials of similar foreign products.
干预措施: CD19/BCMA Targeted CAR T-cells (Drug)
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: Baseline up to 28 days after CAR T-cells infusion
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to 2 years after CAR T-cells infusion
Incidence of treatment-emergent adverse events \[Safety and Tolerability\]
次要结局
- B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)(At Week 4, 12, and Month 6, 12, 18, 24)
- Multiple myeloma (MM), Overall response rate (ORR)(At Day 28)
- B-ALL, Event-free survival (EFS)(Up to 2 years after CAR-T cells infusion)
- B-NHL, disease control rate (DCR)(At Week 12 and Month 6, 12, 18, 24)
- Instrumental Activities of Daily Living (IADL) score(At Baseline, Month 1, 3, 6, 9 and 12)
- Hospital Anxiety and Depression Scale (HADS) score(At Baseline, Month 1, 3, 6, 9 and 12)
- B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)(At Month 1, 3, 6, 12, 18 and 24)
- MM, Overall survival (OS)(At Month 6, 12, 24)
- Quality of life(At Baseline, Month 1, 3, 6, 9 and 12)
- Activities of Daily Living (ADL) score(At Baseline, Month 1, 3, 6, 9 and 12)
- B-ALL, Overall survival (OS)(Up to 2 years after CAR-T cells infusion)
研究者
He Huang
Clinical Professor
Zhejiang University