Safety and Efficacy of hCD1a-CAR T (OC-1) Therapy, in Patients With Relapsed/Refractory (R/R) T-cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/LL
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Number of adverse events grade III-IV
研究概览
简要总结
First in humans, exploratory, open-label, single-arm, multicentre, non-competitive, dose escalation study to assess the safety and efficacy of CD1a-CAR T therapy in patients with relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LL)
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
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children older than 2 years or adults, male and female in both groups.
- •Patients CD1a antigen blast expression ≥20% at inclusion, either immunophenotypically (flow cytometry) or histologically confirmed.
- •R/R CD1a-positive T-ALL/LL patients defined as:
- •Failure to achieve morphological complete remission (> 5% bone marrow blasts) or persistence of extramedullary disease after at least two cycles of chemotherapy.
- •First or subsequent relapse, including morphologic or MRD-detectable (≥1x10-4 ) bone marrow and/or extramedullary relapses after at least one standard frontline therapy.
- •Relapse after allogeneic haematopoietic stem cell transplantation (allo-HSCT).
- •Primary refractoriness, defined as either morphologic persistence or detectable MRD (≥1x10-4 ) after at least two cycles of chemotherapy, making the patient not candidate for allo-HSCT.
- •Patient without reproductive capacity or else, commitment to the use of a highly effective method of contraception during the study.
排除标准
- •Limiting organ dysfunction, such as uncontrolled cardiac (e.g., depressed left ventricular ejection fraction (LVEF), <45%), pulmonary, liver, renal or CNS dysfunction.
- •Allo-HSCT within a time frame <3 months, or requiring continued immunosuppressive treatment for graft versus host disease (GvHD).
- •Uncontrolled epilepsy or underlying central nervous system (CNS) severe disease.
- •Active bacterial, fungal or viral infection not controlled by adequate treatment.
- •Known HIV, active hepatitis B (HBV), or hepatitis C virus (HCV) infection.
- •Women who are pregnant (urine/blood pregnancy test positive) or lactating.
- •Severe illness or medical condition, which would not permit the patient to be managed according to the protocol.
- •Suffering from a serious autoimmune disease or immunodeficiency disease.
- •The patient participated in other experimental drug clinical trial within 6 weeks prior to OC-1 infusion.
- •Other non-controlled concomitant neoplasms.
研究组 & 干预措施
Experimental: CD1a-CAR T
CD1a CAR T cells transduced with a lentiviral vector to express CD1a chimeric receptor domain on T cells administered with a dose-escalation approach.
干预措施: CD1a-CAR T (Biological)
结局指标
主要结局
Number of adverse events grade III-IV
时间窗: 1 year particularly the first 28 days after infusion
Number of adverse events grade III-IV using common toxicity criteria (CTC)
Non-relapse treatment-related mortality (NRM)
时间窗: 1 year
Non-relapse treatment-related mortality (NRM)
Number of patients developing dose limiting toxicity (DLT)
时间窗: first 28 days after infusion
Number of patients developing dose limiting toxicity (DLT)
Incidence of severe Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS)
时间窗: 1 year particularly the first 28 days after infusion
Incidence of severe Cytokine release syndrome (CRS) (≥ grade III) and Immune effector cell-associated neurotoxicity syndrome (ICANS) (≥ grade II)
Number of adverse events of special interest (AESI)
时间窗: 1 year
Number of adverse events of special interest (AESI)
Assessment of the immunological homeostasis
时间窗: 1 year
Assessment of the immunological homeostasis, through the identification of lymphocytes subpopulations by flow cytometry at each study timepoint.
Incidence of the treatment-related dermatological events
时间窗: 1 year
Incidence of the treatment-related dermatological events
次要结局
- Remission rate(1 year)
- Minimal residual disease (MRD) response(1 year)
- Overall survival(1 year)
- Duration of remission(1 year)
- Persistence of OC-1(1 year)
- Progression-free survival (PFS)(1 year)
- Response rates(1 year)
- Complete remission duration (CRD)(1 year)