Safety and Efficacy Study of Novel CAR-T Cell Therapy in the Treatment of Hematopoietic and Lymphoid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- TEAEs
研究概览
简要总结
The primary purpose of this study is to determine the safety and efficacy of novel autologous CAR-T cells in patients with hematopoietic and lymphoid malignancies.
详细描述
Chimeric antigen receptor (CAR)-modified T cells targeted CD19 have demonstrated unprecedented successes. Besides CD19, many other molecules such as CD123, BCMA, and CD7 may be potential in developing the corresponding CAR-T cells to treat patients with hematopoietic and lymphoid malignancies. UTC Therapeutics Inc. have developed an efficient platform for constructing CAR-T cells that can remodel of tumor microenvironment and enhance the anti-tumor immune response and persistence of CAR-T cells. In this study, all eligible subjects will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by investigational treatment, CAR-T cells. Safety, efficacy, pharmacokinetic, and pharmacodynamic of the CAR-T cells will be assessed.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand and the willingness to sign informed consent.
- •Patients with relapsed or refractory Acute Myeloid Leukemia (AML), B-cell Non-Hodgkin's Lymphoma (B-NHL), Multiple Myeloma (MM), Adult T-cell Leukemia/Lymphoma (ATL), B-cell Acute Lymphoblastic Leukemia (B-ALL) after at least two cycles of first-line therapy or autologous hematopoietic stem cell transplantation (auto-HSCT).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0~
- •Adequate organ functions:
- •Sufficient bone marrow function evaluated by investigator to receive lymphodepleting preparative regimen;
- •Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN), or creatinine clearance rate (as estimated by Cockcroft Gault) > 30 mL/min/1.73 m^2;
- •Alanine aminotransferase (ALT) ≤ 5×ULN; and total bilirubin (TBIL) <2.0mg/dL; TBIL of patients with Gilbert's Syndrome or liver involvement must less than 3.0 mg/dL;
- •Left ventricular ejection fraction (LVEF) > 40%.
- •Subjects who have previously received CD19 targeted therapy must have biopsy-proven lymphoma lesions still express CD19 antigen.
排除标准
- •Lymphomas involving only the central nervous system (CNS) (subjects with secondary CNS lymphomas are admitted).
- •History of another malignancy that has not been in remission for at least 2 year (the following conditions may be excluded from the 2-year restriction: non-melanoma skin cancer, completely resected stage I tumor with low probability of recurrence, limited-stage prostate cancer after treatment, biopsy-proven cervical carcinoma in situ, or PAP smear showing squamous epithelium internal lesions).
- •History of treatment with Alemtuzumab within 6 months prior to leukapheresis, or Fludarabine or Cladribine within 3 months prior to leukapheresis.
- •Active hepatitis C (HCV), hepatitis B (HBV), human immunodeficiency virus (HIV), or syphilis infection.
- •Uncontrolled fungal, bacterial, viral, or other infection.
- •Acute or chronic graft-versus-host disease (GVHD).
- •History of any of the following cardiovascular diseases within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stent, myocardial infarction, unstable angina, or other clinically significant heart disease.
- •History or clinical evidence of CNS disease.
- •Female subjects who are pregnant or lactating.
- •Prior CAR-T therapy or other genetically modified T cell therapy.
研究组 & 干预措施
Autologous CAR-T cells
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CAR-T cells. CAR-T cells targeted CD19/BCMA/CD123/CD7 are autologous genetically modified T cells.
干预措施: Autologous CAR-T cells (Biological)
Autologous CAR-T cells
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CAR-T cells. CAR-T cells targeted CD19/BCMA/CD123/CD7 are autologous genetically modified T cells.
干预措施: Fludarabine (Drug)
Autologous CAR-T cells
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CAR-T cells. CAR-T cells targeted CD19/BCMA/CD123/CD7 are autologous genetically modified T cells.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
TEAEs
时间窗: 4 weeks
Incidence and severity of Treatment Emergent Adverse Event.
TRAEs
时间窗: 4 weeks
Incidence and severity of Treatment Related Adverse Events.
AESIs
时间窗: 4 weeks
Incidence and severity of AEs of Special Interest.
次要结局
- Duration of Overall Response (DOR)(12 months)
- Progression-Free Survival (PFS)(12 months)
- Overall survival (OS)(12 months)