The Safety and Clinical Efficacy of Dasatinib Plus Human CD19/CD22 Bispecific CAR-T Cell Therapy for Elderly Subjects With Ph-positive Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Number of patients achieving molecular CR
研究概览
简要总结
To evaluate the safety and efficacy of Dasatinib plus CD19/CD22 Bispecific CAR-T for the treatment of elderly Ph-positive lymphoblastic leukemia. Newly diagnosed Ph-positive patients will be given Dasatinib plus VP chemotherapy for induction treatment,if a hematologic complete remission was observed then a lymphocyte collection will be administrated to patients. Then chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19/CD22 CAR+ T cells
详细描述
Newly diagnosed ph-positive ALL patients over 60 and less than 70 years old will be enrolled. Patients will be given Dasatinib plus VP chemotherapy for induction remission treatment, if a hematologic complete remission was observed then a lymphocyte collection will be administrated to patients. Then chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19/CD22 CAR+ T cells
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
- 55 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(1)55 to 70 Years Old, Male and female;
- •(2) Newly diagnosed Ph-positive ALL
- •(3) ECOG score 0-1;
- •(4) The venous access required for collection can be established and mononuclear cell collection can be determined by the investigators;
- •(5) Liver, kidney and cardiopulmonary functions meet the following requirements:
- •Creatinine is in the normal range;
- •Left ventricular ejection fraction >50%;
- •Baseline oxygen saturation>92%;
- •Total bilirubin ≤ 1.5×ULN;
- •ALT and AST ≤ 2.5×ULN;
- •(6) Able to understand and sign the Informed Consent Document
排除标准
- •(1) Disease relapse;
- •(2) Malignant tumors other than acute lymphoblastic leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection;
- •（3) ECOG >=2 during CAR-T therapy
- •(4) Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease; Heart disease including the following condition
- •Ultrasound shows left ventricular ejection fraction <50%;
- •stable/unstable angina,myocardia infarction
- •Baseline oxygen saturation>92%;
- •history of pacemaker inplantation
- •more than 2 leads ST segments decrease>1mm,or more than 2 consecutive leads T wave inversion;
- •Long QT syndrom
- •A severe arrhythmia requiring medical treatments
- •bradycardia,HR<50BPM I.QTc>450ms
- •(5)Uncontrolled infection during screening peroid; Hemodynamic instability associated with infection,a new infection or aggravation of the original infection;new lesions on imaging;fever of unkown cause
- •(6) Patients with symptoms of central nervous system;greater than grade 2 requring treatment,paralysis,aphasia,acute cerebral infarction,severe traumatic brain injury,schizophrenia
- •(7)Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell transfusion;
- •(8) HIV infection
- •(9)Subjects with positive HBsAg or HBcAb and peripheral blood HBV DNA titer detection ≥ 1 × 102 copy number / L; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; CMV DNA positive; syphilis positive;
- •(10) Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion;
- •(11) allergy to Dasatinib
- •(12) history of autoimmune disaese
研究组 & 干预措施
Dasatinib plus anti-CD19/CD22 CAR-T cells
Administration with oral Dasatinib plus anti-CD19/ CD22 CAR-T cells in the elderly Ph-positive ALL patients.
干预措施: Dasatinib plus anti-CD19/CD22 CAR-T cells (Drug)
结局指标
主要结局
Number of patients achieving molecular CR
时间窗: 3 months after infusion of Anti-CD19/CD22 CAR-T cells
number of patients achieving molecular CR
次要结局
- RFS for patients receiving infusion of anti-CD19/CD22 CAR-T cells(2-year RFS)
- Number of patients achieving molecular CR(6 months after infusion of Anti-CD19/CD22 CAR-T cells)
- OS for patients receiving infusion of anti-CD19/CD22 CAR-T cells(2-year OS)
研究者
Xianmin Song, MD
principal investigator
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine