Phase I/II Study to Evaluate Treatment of Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T Adoptive Cellular Immunotherapy With CAR-T Cells Targeting CD38
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
研究概览
简要总结
CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19 in tumor cells. CD38 CAR-T cells can recognize and kill the CD19 negative malignant cells through recognition of CD38. This is a phase 1/2 study designed to determine the safety of the gene-edited specificity CD38 CAR-T cells and the feasibility of making enough to treat patients with relapsed B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular immunotherapy.
详细描述
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PRIMARY OBJECTIVES:
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To evaluate the feasibility and safety of specificity CD38 CAR-T cells in patients with relapsed or refractory leukemia and lymphoma.
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To evaluate the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells.
Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM and lymph node will be used to detect and quantify survival of CD38 CAR-T cells over time. 2. SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-tumor response due to specificity CD38 CAR-T cell infusions.
- The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using Day 0: 1-5x10e6/kg total dose on day 0.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participant
- •12 Years to 70 Years (Child, Adult, Senior)
- •Patient with relapsed CD38+ B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular immunotherapy
- •Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- •Adequate organ function
排除标准
- •Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
- •Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
- •Richter's syndrome
- •Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
- •Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
- •Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
- •Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
- •Patient has an investigational medicinal product within the last 30 days prior to screening
- •Previous treatment with investigational gene or cell therapy medicine products
- •Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
- •Pregnant or nursing women
结局指标
主要结局
Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
时间窗: 24 weeks
Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes
时间窗: 24 weeks
MTD of specificity CD38 CAR-T cells
时间窗: 4 weeks
The highest dose of specificity CD38 CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of specificity CD38 CAR-T cells.
次要结局
- Six-month Objective response rate of complete remission and partial remission(24 weeks)
- Six-month Progression free survival(24 weeks)
- Six-month Overall survival(24 weeks)
研究者
Han weidong
Director of Molecular & Immunological Department,Biotherapeutic Department
Chinese PLA General Hospital