Anti-CD7 Protein Expression Blocker (PEBL) Chimeric-Antigen Receptor (CAR) T-Cell Therapy for Relapsed/ Refractory T-Lineage Acute Lymphoblastic Leukaemia (CARTALL)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Proportion of participant who are flow cytometry minimal residual disease (MRD) negativity at 1 month after Anti-CD7 PEBL CAR T-cell infusion.
研究概览
简要总结
The objective of this study is to assess the safety and efficacy of anti-CD7 CAR T-cells in patients with refractory or relapsed T-lineage acute lymphoblastic leukemia (T-ALL).
详细描述
A major obstacle to the development of effective CAR T-cells for T-cell malignancies is that the surface marker profile of malignant T-cells largely overlaps that of activated T lymphocytes. We developed a CAR T-cell approach that targets CD7, a T-cell marker highly expressed in all cases of T-cell ALL, including ETP-ALL. Its expression is also highly stable even in T-ALL cells exposed to chemotherapy. To prevent fratricide effect of the T cells, surface CD7 expression are effectively downregulated with the expression of an anti-CD7 Protein Expression Blocker (PEBL). Patients will receive anti-CD7 PEBL CART-cells. This will allow targeting the entire leukemia cell population to induce deeper and more durable remissions.
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
- 6 Months 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis/ Disease define as:
- •Relapsed T-cell acute lymphoblastic leukaemia/ lymphoma as defined by:
- •Bone marrow disease = or > 0.01% by MRD as determined by flow cytometry
- •Or CNS disease as defined as > 5 WBCs/ uL in CSF with morphological evidence of blasts or biopsy proven recurrence in the eye or brain
- •Or Extramedullary relapse as defined by morphological evidence of blasts in the testis or any other extramedullary sites
- •Induction failure as defined by:
- •MRD = or > 1% by flow cytometry at the end of induction on day 33
- •Or Failure to achieve morphological remission defined as > 5% blasts after standard induction chemotherapy
- •Refractory disease as defined by:
- •MRD = or > 0.01% by flow cytometry or molecular methods during 2 or more timepoints after induction therapy
- •Minimum level of pulmonary reserve defined as Grade ≤ 1 dyspnoea and oxygen saturation (SpO2) of > 95% on room air
- •Left ventricular systolic function (LVSF) ≥ 28% confirmed by echocardiogram, or left ventricular ejection fraction (LVEF) ≥ 45% confirmed by echocardiogram within 3 months of screening
- •Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50 at screening
- •Normal Age-adjusted eGFR Creatinine Clearance within 3 months of screening
- •Alanine aminotransferase ≤ 5 times the upper limit of normal for age
- •Patients with > 99% CD7 expression on blast cells will be eligible for anti-CD7 PEBL-CAR-T cell infusion.
排除标准
- •Failure to meet any of the inclusion criteria
- •Patients who test positive on urine pregnancy testing and are pregnant or are lactating
- •Concomitant genetic syndromes associated with bone marrow failure states, such as Fanconi anaemia, Kostmann syndrome, Schwachman syndrome, or any other bone marrow failure syndrome with the exception of Down syndrome
- •Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and no evidence of active disease
- •Active or latent hepatitis B or hepatitis C infections within 8 weeks of screening, or any uncontrolled infection at screening
- •Positive Human Immunodeficiency Virus (HIV) test within 8 weeks of screening
- •Grade 2 to 4 acute graft-vs-host disease (GVHD) or extensive chronic GVHD
- •Received an investigational medicinal product within 30 days of screening
- •Central nervous system : Uncontrolled seizures or status epilepticus; increased intra-cranial pressure as evidenced by papilledema and CSF opening pressure > 20 cm water; decreased conscious state (any cause)
结局指标
主要结局
Proportion of participant who are flow cytometry minimal residual disease (MRD) negativity at 1 month after Anti-CD7 PEBL CAR T-cell infusion.
时间窗: 30 days
MRD levels will be determined by flow cytometry. The target sensitivity of flow MRD is \<0.01% when available.
次要结局
- Proportion of participant who are minimal residual disease (MRD) negative with molecular base assay at the end of 1 month after Anti-CD7 PEBL CAR T-cell infusion.(30 days)
- Proportion of patient who shows CAR T-cell persistence by immunophenotyping using flow cytometry in bone marrow, peripheral blood and CSF samples at multiple study time points following CAR T cell infusion(1 month to 5 years)