Clinical Study on the Safety and Efficacy of Bedside CD19 CAR T-cell Therapy for B-cell Acute Lymphoblastic Leukemia
概览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 发起方
- The General Hospital of Western Theater Command
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- the incidence rate of CAR-T-related adverse events
概览
简要总结
The purpose of this clinical trial is to learn if autologous bedside CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy works to treat B-cell acute lymphoblastic leukemia (B-ALL) in adults. It will also learn about the safety and efficacy of the autologous bedside CD19 CAR-T cell product.
The main questions it aims to answer are:
- What adverse events occur and the incidence rate of dose-limiting toxicities (DLTs) within 28 days and CAR-T-related adverse events (AEs) after the autologous CD19 CAR-T cell infusion for B-ALL?
- Which dose level is the optimal biological dose (OBD)?
- What is the rate of minimal residual disease (MRD) negativity, complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), duration of response (DOR), and overall survival (OS)?
Participants will:
- Receive autologous bedside CD19 CAR T-cell therapy on Day 0.
- Be hospitalized for at least 7 days post-infusion for close safety monitoring and remain within 2 hours of the treatment facility for at least 28 days.
- Visit the clinic at Day 7, Day 14, Day 28, then monthly for up to 12 months after CAR-T cells infusion, with continued long-term follow-up for safety and persistence.
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
- •Age 18 to 70 years inclusive at the time of signing informed consent.
- •Documented diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) according to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Acute Lymphoblastic Leukemia (2018, Version 1) or World Health Organization (WHO) classification criteria.
- •CD19 expression confirmed by flow cytometry, immunohistochemistry, or pathology on bone marrow, peripheral blood, or tissue specimens. For patients for whom current sampling is not clinically feasible, results from testing performed within 60 days prior to informed consent may be acceptable, as determined by the investigator.
- •Life expectancy ≥12 weeks in the opinion of the investigator.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or
- •Adequate organ function as demonstrated by the most recent assessment during the screening period, defined as:
- •Creatinine clearance ≥60 mL/min (calculated using the Cockcroft-Gault formula)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × upper limit of normal (ULN)
- •Total bilirubin ≤1.5 × ULN (for patients with documented Gilbert's syndrome, total bilirubin ≤2.5 × ULN is acceptable)
- •For women of childbearing potential (WOCBP), a negative serum pregnancy test must be documented within 7 days prior to enrollment. WOCBP and male patients with partners who are WOCBP must agree to use highly effective contraceptive methods from the screening period through 12 months after CAR-T cell infusion. Women are considered not of childbearing potential if they are postmenopausal for at least 1 year or have documented evidence of surgical sterilization or congenital infertility. Women who are pregnant or breastfeeding are excluded from this study.
排除标准
- •Patients meeting any of the following criteria are not eligible for enrollment:
- •Active central nervous system (CNS) involvement by B-ALL, defined as CNS-2 or CNS-3 status according to standard criteria.
- •History of another malignancy within 2 years prior to screening, except for adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
- •Patients who previously received CAR-T cell therapy and experienced Grade ≥4 cytokine release syndrome (CRS) or neurotoxicity are specifically excluded.
- •Treatment with any investigational or approved anti-B-ALL therapeutic agent within 5 half-lives prior to enrollment (excluding supportive care medications).
- •Radioimmunotherapy or radiotherapy within 8 weeks prior to enrollment.
- •Receipt of live attenuated vaccine within 4 weeks prior to screening.
- •Current or anticipated use of systemic corticosteroids at high dose (defined as a total cumulative dose equivalent to ≥60 mg dexamethasone or equivalent corticosteroid) within 4 weeks prior to lymphodepletion chemotherapy. Physiologic replacement doses, topical, inhaled, nasal, and ophthalmic corticosteroids are permitted.
- •Active acute or chronic graft-versus-host disease (GVHD) requiring systemic treatment within 4 weeks prior to CAR-T cell infusion.
- •Major surgical procedure within 3 months prior to screening.
研究组 & 干预措施
CAR T-cell treatment
干预措施: CD19 CAR T cells (Drug)
结局指标
主要结局
the incidence rate of CAR-T-related adverse events
时间窗: Up to 28 days after injection
Incidence of adverse events(AEs) after infusion, The number, frequency, severity, and laboratory findings of all treatment-related adverse events/serious adverse events are included. Description, time, classification, and outcome of AE events resulted from the investigational medical product, delivery method, or emergency measures will be recorded in the case report form.
The incidence rate of Dose limited toxicity (DLTs)
时间窗: Up to 28 days after infusion
Dose limited toxicity(DLT) was defined as the occurrence of any of the following adverse events within 28 days of the infusion of CAR-T cells after optimal supportive treatment, which were discussed with the investigator and determined to be associated or likely to be associated with the infusion. Any DTLs within 28 days after CAR-T infusion will be recorded in time, including severity, occurrence time, duration, treatment methods and prognosis.
次要结局
- the rate of minimal residual disease (MRD) negativity(up to 1 year after CAR-T cells infusion)
- overall response rate (ORR)(up to 1 year after CAR-T cells infusiion)
- Duration of Response (DOR)(up to 1 year after CAR-T cells infusion)
- overall survival (OS)(up to 1 year after CAR-T infusion)
研究者
Yihai2024
Head of department of hematology
The General Hospital of Western Theater Command