Efficacy and Safety of Molecular Targeted Therapy Combined With Chemotherapy and Sequential CAR-T Cells in Newly Diagnosed Adult Patients With Philadelphia Chromosome-Positive B-cell Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 82
- 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 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+ ALL patients achieving complete remission (CR) with overembatinib, venetoclax and reduced-intensity 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.The study endpoints include 2-year disease-free survival (DFS) rate, overall survival (OS) rate, event-free survival (EFS) rate, cumulative molecular remission rate, immune repertoire-minimal residual disease (MRD) remission rate, cumulative relapse rate, treatment-related toxicities, and quality of life. Additionally, an interim analysis will be conducted, with the 1-year DFS rate as the key index for this analysis.
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
- •Male or female patients aged 18 years or older
- •Newly diagnosed Philadelphia chromosome positive(either t(9;22) and/or BCR-ABL positive and/ or FISH positive) acute lymphoblastic leukemia
- •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
- •Lymphoid blast crisis of chronic myelocytic leukemia (CML)
- •Previous or ongoing systemic anti-ALL therapy (including but not restricted to TKI and/or radiotherapy, except for appropriate pre-treatment)
- •Patients with a history of myocardial infarction within 12 months or clinically significant cardiac disorders disease (e.g., unstable angina, congestive heart failure, uncontrollable hypertension, uncontrollable arrhythmia, etc.)
- •Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
- •Known HIV seropositivity
- •History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis
- •Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
- •Another malignancy diagnosed and treated within 5 years prior to diagnosis or previously diagnosed with another malignancy with evidence of residual disease. Patients with non-melanoma skin cancer or any type of carcinoma in situ that has been completely excised should not be excluded
- •Female patients who are pregnant or breast feeding
- •Clinical manifestations of active CNS or extramedullary involvement with ALL
- •Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded
- •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
TKI Combined With Chemotherapy and Sequential CAR-T Cells
Ph+ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with overembatinib, venetoclax and reduced-intensity chemotherapy.
干预措施: CAR-T cells (Combination Product)
TKI Combined With Chemotherapy and Sequential CAR-T Cells
Ph+ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with overembatinib, venetoclax and reduced-intensity chemotherapy.
干预措施: Venetoclax (Drug)
TKI Combined With Chemotherapy and Sequential CAR-T Cells
Ph+ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with overembatinib, venetoclax and reduced-intensity chemotherapy.
干预措施: Olverembatinib (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)
- Cumulative rate of complete molecular response(Up to 1 year post-registration)
- MRD-negative complete remission rate measured by NGS tracking clonal IG/TR rearrangements(Up to 1 year post-registration)
- The rate of adverse(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)