Efficacy and Safety of Chemotherapy Combined With CAR-T Cells in Newly Diagnosed Adult Patients With Philadelphia Chromosome-Negative B-cell Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 77
- 试验地点
- 1
- 主要终点
- Disease-free Survival (DFS)
研究概览
简要总结
In recent years, immunotherapy (eg. blinatumomab, inotuzumab ozogamicin, CAR-T cells) has demonstrated a high safety and efficacy profile in relapsed/refractory (R/R）B-ALL. The available data suggest that the advancement of immunotherapy from relapsed/refractory (R/R) field to the frontline setting may be an important approach to increase the depth of remission, which ultimately translates into a survival benefit. In this study, the investigators propose a treatment regimen using CAR-T cell therapy as a consolidation method for Ph- B-ALL patients achieving complete remission (CR) with chemotherapy, aiming to reduce the total cycles of chemotherapy and related toxicities, shorten length of hospitalization, and ultimately improve patients' survival and quality of life.
详细描述
The CAR-T cells were murine-derived second-generation CD19 CAR-T with a co-stimulation domain of 4-1BB, and the infusion dose was 1×10^6/kg CAR+ cells in a single infusion.
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
- •De novo and primary Ph/BCR-ABL1 negative acute lymphoblastic leukemia diagnosed by the bone marrow cytomorphology, immunophenotyping, cytogenetics and molecular biology according to WHO classification
- •Male or female patients aged 18 years or older
- •CD19 expression on blasts
- •Expected survival time greater than 3 months
- •Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of normal（ULN）; serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤5 x ULN if leukemic involvement of the liver is present; Creatinine ≤ 1.5 x ULN; Serum amylase and lipase ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related; normal electrolytes: Potassium ≥ LLN; Magnesium ≥ LLN; Phosphorus ≥ LLN; Cardiac color Doppler ultrasound ejection fraction ≥ 45%
- •Subject has provided written informed consent prior to any screening procedure
排除标准
- •Burkitt lymphoma/leukemia
- •Acute Leukemia of Ambiguous Lineage
- •Clinical manifestations of active CNS or extramedullary involvement with ALL
- •Female patients who are pregnant or breast feeding
- •Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
- •Known HIV seropositivity
- •Clinically significant ventricular arrhythmias, unexplained syncope (not vasovagal) or sinus block, history of chronic bradycardia with a high degree of atrioventricular (AV) conduction block (unless a permanent pacemaker is implanted)
- •Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment
- •Other conditions assessed by the investigators to be inappropriate for this study
研究组 & 干预措施
Chemotherapy and Sequential CAR-T Cells
Ph-ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with pediatric-inspired regimen and venetoclax.
干预措施: CAR-T cells (Combination Product)
Chemotherapy and Sequential CAR-T Cells
Ph-ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with pediatric-inspired regimen and venetoclax.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Disease-free Survival (DFS)
时间窗: Up to 2 years post-registration
From CR1 to relapse, death from any cause or last follow-up
次要结局
- Event-free survival (EFS)(Up to 5 years post-registration)
- Overall survival (OS)(Up to 5 years post-registration)
- Cumulative incidence of relapse (CIR)(Up to 2 years post-registration])
- The rate of adverse events(Up to 5 years post-registration)
- MRD-negative complete remission rate measured by flow cytometry.(After induction (4 week)])
- MRD-negative complete remission rate measured by NGS tracking clonal IG/TR rearrangements(Up to 1 year post-registration)