Safety and Efficacy of Anti-CD7 CAR-Engineered T Cells for Relapsed/Refractory T Lymphoid Malignancies: a Single-center, Open-label, Non-randomized, Single-arm Clinical Study
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-related Adverse Events
研究概览
简要总结
This is a single-center, open-label, single-arm study to evaluate the primary safety and efficacy of anti-CD7 chimeric antigen receptor(CAR)-modified T cells(CAR7-Ts) in patients with relapsed or refractory T lymphoid malignancies.
详细描述
Chimeric antigen receptor-T cells (CAR-T) have made breakthroughs in the treatment of B-cell tumors, especially refractory/relapsed acute B lymphocytes. CD7 is a transmembrane glycoprotein expressed by T cells and natural killer cells and their precursors; it is also expressed in >95% of lymphoblastic T-cell leukemias and lymphomas . CD7 was previously evaluated as a target for immunotoxin-loaded antibodies in patients with T-cell malignancies, but tumor responses were limited.
Enhancing the potency of CD7-directed cytotoxicity by substituting donor-derived CAR-T cells for a monoclonal antibody would augment the efficacy of CD7-targeted therapy in patients with T-cell malignancies. To prepare CAR7-T cells, CD7 expression is suppressed on donor-derived T cells by unique blocking technique, and CD7-negative T cells are transduced with a humanized anti-CD7-41BB-CD3ζ lentiviral vector.
This is an investigational study. The objectives are to evaluate the safety and efficacy of CAR7-T cells in patients with CD7+ T-cell malignancies.
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
- 14 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged from 14 to 70 years;
- •Expected survival over 60 days;
- •Eastern Cooperative Oncology Group score 0-2;
- •Diagnosed as T-cell hematologic malignancies (including leukemia and lymphoma) according to WHO2016 criteria;
- •Patients must relapse or be refractory after at least two lines of therapy.
- •CD7 were positive in bone marrow or cerebrospinal fluid by immunohistochemistry or flow cytometry at screening, and one of the following conditions is satisfied:
- •A. No remission was achieved after at least 2 lines of standard therapy; B. Relapse or progression after standard treatment; C. Relapse after autologous or allogeneic hematopoietic stem cell transplantation;
- •Have no fertility requirements or plans for one year since enrollment in this clinical trial;
- •Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
排除标准
- •Complicated with central system leukemia/lymphoma with active intracranial lesions;
- •Existing or preexisting CNS conditions, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS related autoimmune disease;
- •Symptomatic heart failure or severe arrhythmias;
- •Symptoms of severe respiratory failure;
- •Complicated with other types of malignant tumors;
- •Serum creatinine and/or urea nitrogen ≥ 1.5 times of normal value;
- •Suffer from sepsis or other uncontrollable infections;
- •Intracranial hypertension or brain consciousness disorder;
- •Severe mental disorders;
- •Have received organ transplantation (excluding bone marrow transplantation);
- •Female patients (fertile patients) had positive blood HCG test;
- •Hepatitis (including hepatitis B and C), AIDS and syphilis were screened positive;
- •Patients with graft-versus-host disease (GVHD) or who require immunosuppressant treatment;
- •The absolute value of lymphocytes was too low to manufacture CART cells;
- •Other conditions considered inappropriate by the researcher.
研究组 & 干预措施
Fludarabine + Cyclophosphamide + anti-CD7 CAR-T Cells
Patients will received lymphodepletion with fludarabine (30 mg/kg) and cyclophosphamide (250 mg/kg) on day -5, -4, and -3, followed by the infusion of CAR7-T cells with the dose of 1×10^6/kg and 2×10^6/kg (with an allowance of ±20%). If no dose-limited toxicity (DLT) emerges in the group, then the subsequent higher dose will be used in the next group. If DLT emerges in a single subject in any dose level, 3 more subjects will be enrolled to the same dose level. The maximum dose could be extended.
干预措施: Fludarabine + Cyclophosphamide + CAR7-T Cells (Drug)
结局指标
主要结局
Incidence of Treatment-related Adverse Events
时间窗: within 2 years after infusion
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
次要结局
- Overall response rate(ORR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.(within 2 years after infusion)
- Complete response rate(CRR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.(within 2 years after infusion)
- Progress-free survival(PFS) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.(within 2 years after infusion)
- Duration of Response(DOR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.(within 2 years after infusion)
- Overall survival(OS) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.(within 2 years after infusion)
研究者
MEI HENG
Proferssor, Cheif Doctor
Wuhan Union Hospital, China