An Open, Prospective, Single-arm Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Allogeneic Anti CD19 CAR-T Combined With a Novel Third-generation TKI Olverembatinib in Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Incidence of adverse events (AEs)
研究概览
简要总结
This is an Open, Prospective, Single-arm Study, which is designed to evaluate the efficacy, safety and pharmacokinetics of ThisCART19A Combined With Olverembatinib for the treatment of Newly Diagnosed Ph-positive lymphoblastic leukemia.
详细描述
To evaluate the efficacy, safety and pharmacokinetics of ThisCART19A Combined With Olverembatinib for the treatment of Ph-positive lymphoblastic leukemia. Newly diagnosed Ph-positive patients will be given VP chemotherapy for induction treatment until the leukocyte count is less than 10×109/L. Then chemotherapy regimen of fludarabine and cyclophosphamide followed by a infusion of ThisCART19A. These patients will combination with Olverembatinib as maintenance therapy based on the hematologic complete remission of leukemia after 4 weeks of treatment.
Patients could receive an additional infusion of ThisCART19A if they achieved initial benefit and subsequently minimal residual disease positive (defined as Flow-cytometric MRD≥0.1%) during maintenance treatment. Additionally, a subset of patients which achieved complete molecular remission over 6 month were eligible for a second planned infusion as a consolidation therapy .
During the treatment, lumbar puncture combined with sheath injection will be performed to prevent central nervous system leukemia (CSNL). If CNSL occurs at the time of admission, patients should receive regular conventional lumbar puncture and sheath injection for treating CNSL.
During the treatment, each subject will be evaluated regularly, including hematological response, FCM-MRD, cytogenetic response and molecular remission rate, as well as adverse events. EFS and OS will be followed up for 2 years.
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 non-pregnant, non-lactating female patients who are 18 years of age or older.
- •Newly diagnosed Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL, as defined by the 2016-WHO criteria. Participants should not be treated with any kind of TKIs or chemotherapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, and expected survival period ≥ 3 months.
- •Organ function as indicated by the following laboratory indicators must be met:
- •1. Alanine aminotransferase (ALT) ≤ 5×upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 5×ULN;
- •Total bilirubin<2×ULN;
- •24-hour calculated creatinine clearance>30 mL/min;
- •Cardiac ejection fraction (EF)≥40%;
排除标准
- •Active hepatitis B virus (defined as serum HBV-DNA ≥ 2000 IU/mL), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or active syphilis infection prior to enrollment. (Subjects with HBV-DNA < 2000 IU/mL can be enrolled, but should be administered antiviral drugs such as entecavir and tenofovir with relative clinical indicators monitored simultaneously during the treatment.) ;
- •Uncontrolled active infection;
- •Patients who are currently suffering from active autoimmune disease or a history of autoimmune disease potentially involving the CNS;
- •Patients who have any history of heart or vascular disease, such as hypertension (systolic blood pressure(HBP) > 140mmHg and/or diastolic blood pressure > 90mmHg);
- •Cardiac ultrasonography indicates that pulmonary artery systolic blood pressure is >50 mmHg; or there are clinical symptoms related to pulmonary arterial hypertension;
- •Patients who suffer from severe bleeding disorders unrelated to Ph+ ALL;
- •Patients who have any other malignant tumors that require treatment;
- •Patients who have severe hypertriglyceridemia (triglyceride ≥ 5.6mmol/L);
- •Patients who are pregnant, planning to become pregnant or breastfeeding;
- •Patients who underwent major surgery (except for minor surgery such as catheter placement or bone marrow biopsy) within 14 days before the first drug;
- •Patients who may not be able to complete all study visits or procedures required by the study protocol, including follow-up visits, and/or fail to comply with all required study procedures;
- •Patients who suffer from any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the safety of the research drug.
研究组 & 干预措施
Treatment Group
ThisCART19A cells infusion, Given intravenously，Combined With Olverembatinib, Given PO
干预措施: ThisCART19A (Drug)
Treatment Group
ThisCART19A cells infusion, Given intravenously，Combined With Olverembatinib, Given PO
干预措施: Cyclophosphamide (Drug)
Treatment Group
ThisCART19A cells infusion, Given intravenously，Combined With Olverembatinib, Given PO
干预措施: Fludarabine (Drug)
Treatment Group
ThisCART19A cells infusion, Given intravenously，Combined With Olverembatinib, Given PO
干预措施: Olverembatinib (Drug)
结局指标
主要结局
Incidence of adverse events (AEs)
时间窗: 2 years
Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The proportion of patients with AEs will be estimated, along with the Bayesian 95% credible interval.
Number of Participants with Complete Molecular Remission
时间窗: 3 months
Will be estimated along with the 95% credible intervals. Complete molecular response (CMR) was defined as the absence of a detectable BCR-ABL1 transcript with a sensitivity of 0.01%.
次要结局
- Objective Response Rate (ORR)(2 years)
- Duration of Complete Molecular Remission(From the date of acquisition of complete molecular remission until the date of loss of complete molecular remission, assessed up to 2 years.)
- Event-free survival (EFS)(From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 2 years)
- Overall survival (OS)(From the first day of treatment to time of death from any cause, assessed up 2 years)