A Phase I Clinical Trial of Anti-CD19 Chimeric Antigen Receptor in PiggyBac Transposon-Engineered T Cells for the Treatment of Patients With Relapsed/Refractory/High-risk B-cell Lymphoma or B-cell Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Grade and number of cytokine release syndrome and neurotoxic effects in participants receiving treatment
研究概览
简要总结
Our previous study demonstrated that anti-CD19 chimeric antigen receptor in piggyBac transposon-engineered T cells have strong tumor-killing activity in vitro and therapeutic effects in cell line-derived xenograft models, and no obvious side effects such as neurotoxicity and cytokine storm occurred. Therefore, we want to evaluate the safety and clinical effect of anti-CD19 CAR-T cells in clinical trials.
详细描述
Using piggyBac transposon/transposase system to deliver genes into primary human T cells - example expression of CD19 CAR.CARs specific to the human CD19 antigen were used. All CARs contained the scFv against human CD19 (clone FMC-63), The third BBz CD28z CAR consisted of the scFv linked to the intracellular domains of CD28, 4-1BB and CD3z through a CD28 transmembrane domain;
Subjects with relapsed/refractory CD19-positive B-cell Lymphoma or B-ALL can participate if all eligibility criteria are met. All patients received chemotherapy with fludarabine and cyclophosphamide before the infusion of anti-CD19 CAR-T cells.. After the infusion, subjects will accept follow-up for side effects and effect of anti-CD19 CAR-T cells.
Follow-up :
Safety and adverse events (safety and tolerability of anti-CD19 CAR-T cell therapy within 14 days): The number and severity of adverse events, an evaluation of their association with the anti-CD19 CAR-T cell treatment, and the outcome of the adverse events. Possible adverse events include cytokine release syndrome, hypotension, reversible neurotoxicity, hypogammaglobulinemia, etc. CT was used to evaluate B-lymphoma lesions. B-ALL bone marrow samples were collected by bone marrow aspiration to assess minimal residual disease. Flow cytometry was used to detect proportion of T cells, B cells, and NK cells in the blood, and expression of CD3, CD4, CD8, anti-CD19 CAR to determine the effect of anti-CD19 CAR-T treatment. Plasma levels of the cytokines IFN-gamma, TNF-α, IL-2, GM-CSF, IL-10, and IL-6 were also determined.
Data analysis:
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
- •Patients or their legal guardians voluntarily participate and sign the Informed Consent Document;
- •Male or female patients aged 18 to 70 years (inclusive);
- •Pathologically and histologically confirmed CD19 + B cell tumors; Patients currently have no effective treatment options, such as chemotherapy or relapse after hematopoietic stem cell transplantation; Or patients voluntarily choose transfusion of anti-CD19 CAR-T cells as the first treatment program;
- •B-cell tumors / lymphomas and B-cell acute lymphoblastic leukemia include the following four types:1) B-cell acute lymphoblastic leukemia;2) Indolent B-cell lymphomas;3) Aggressive B-cell lymphoma; 4) Multiple myeloma;
- •(1) Residual lesions remain after treatment and Not suitable for Hematopoietic stem cell transplantation (auto/allo-HSCT); (2) Relapse after Complement receptor 1 (CR1) and unsuitable for HSCT; (3) Patients with high risk factors; (4) Relapse or no remission after hematopoietic stem cell transplantation or cell immunotherapy.
- •Have measurable or evaluable tumor foci;
- •Liver, kidney and cardiopulmonary functions meet the following requirements:
- •Serum glutamic pyruvic transaminase (ALT) and serum glutamic oxaloacetic transaminase (AST) <3 ×upper limit of normal (ULN);2) Total bilirubin ≤34.2μmol/L;3) Serum creatinine<220μmol/L;4) Baseline oxygen saturation≥95%;5) Left ventricular ejection fraction（LVEF）≥40%.
- •Subjects who did not receive Chemotherapy, Radiotherapy, Immunotherapy (immunosuppressive drugs) or other treatment within 4 weeks prior to enrollment; Relevant toxicity≤1 grade before enrollment (except for low toxicity such as hair loss);
- •Peripheral superficial venous blood flow is smooth, which can meet the needs of intravenous drip;
- •Clinical performance status of eastern cancer cooperation group (ECOG) score ≤2,Expected survival≥3 months;
排除标准
- •Pregnant (urine/blood pregnancy test positive) or lactating women;
- •Planned pregnancy during treatment or within 1 year after treatment, or a male subject whose partner plans pregnancy within 1 year of their cell transfusion;
- •Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment;
- •Active or uncontrollable infection within four weeks prior to enrollment;
- •Patients with active hepatitis B/C;
- •HIV-infected patients;
- •Severe autoimmune or immunodeficiency disorders;
- •Patients are allergic to macromolecule drugs such as antigens or cytokines;
- •Subjects participated in other clinical trials within 6 weeks before enrollment;
- •Systematic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones);
- •Mental illness;
- •Drug abuse/addiction;
- •The investigators consider other conditions unsuitable for enrollment.
结局指标
主要结局
Grade and number of cytokine release syndrome and neurotoxic effects in participants receiving treatment
时间窗: 14 day
Anti-CD19 CAR-T cells growing use requires further education/training and prompt management of safety and tolerability.
Persistence of anti-CD19 CAR-T cells in participants
时间窗: 1 year
Copies numbers of CAR in peripheral blood (PB)
次要结局
- Progress Free Survival(3 years)
- Duration of Response after administration(3 years)
- Overall survival(3 years)