NCT03590574终止1 期
A Single Arm, Open Label, Multi-centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO4, a CAR T-cell Treatment Targeting TRBC1, in Patients With Relapsed or Refractory TRBC1 Positive Selected T Cell Non-Hodgkin Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 5
- 主要终点
- The Numbers of Patients With Grade 3 to 5 Toxicity Occurring Within 60 Days of AUTO4 Infusion.
研究概览
简要总结
The purpose of this study is to test the safety and efficacy of AUTO4 a chimeric antigen receptor (CAR) T cell treatment targeting TRBC1 in patients with relapsed or refractory TRBC1 positive selected T-Non-Hodgkin Lymphoma (NHL).
详细描述
The study will consist of 2 phases, a Phase I/dose escalation phase and a Phase II/expansion phase. Patients with relapsed or refractory TRBC1 positive selected T-NHL will be enrolled in both phases of the study. Eligible patients will undergo leukapheresis to harvest T cells, the starting material for the manufacture of the autologous CAR-T product AUTO4. Following preconditioning by a chemotherapeutic regimen, the patient will receive AUTO4 intravenously as a single dose following which they will then enter a 24-month follow-up period
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged ≥ 18 years.
- •Willing and able to give written, informed consent to be screened for TRBC1 positive T-NHL and to enter the main study.
- •Confirmed diagnosis of selected T-NHL, including:
- •Peripheral T cell lymphoma not otherwise specified, or
- •Angioimmunoblastic T cell lymphoma, or
- •Anaplastic large cell lymphoma
- •Confirmed TRBC1 positive tumour.
- •Relapsed or refractory disease and have had ≥1 prior lines of therapy.
- •Positron emission tomography (PET)-positive measurable disease per Lugano classification.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or
- •Adequate bone marrow function without the requirement for ongoing blood products.
- •Adequate renal, hepatic, pulmonary, and cardiac function.
- •For females of childbearing potential (defined as < 2 years after last menstruation or not surgically sterile), a negative serum or urine pregnancy test must be documented at screening, prior to pre-conditioning and confirmed before receiving the first dose of study treatment. For females who are not postmenopausal (< 24 months of amenorrhea) or who are not surgically sterile (absence of ovaries and/or uterus), a highly effective method of contraception together with a barrier method must be used from the start of the pre-conditioning stage and for at least 12 months after the last dose of AUTO4 (study treatment). They must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 12 months after receiving the last dose of study drug
- •For males, it must be agreed that 2 acceptable methods of contraception are used.
- •No contra-indications for leukapheresis, or the pre-conditioning regimen.
排除标准
- •Patients meeting any of the following exclusion criteria must not be enrolled into the study:
- •Patients with T cell leukaemia.
- •Females who are pregnant or lactating.
- •Prior treatment with investigational gene therapy or approved gene therapy or genetically engineered cell therapy product or allogeneic stem cell transplant.
- •Known history or presence of clinically relevant central nervous system (CNS) pathology. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the CNS.
- •Current or history of CNS involvement by malignancy.
- •Clinically significant, uncontrolled heart disease.
- •Patients with evidence of uncontrolled hypertension or with a history of hypertension crisis or hypertensive encephalopathy.
- •Patients with a history (within 3 months) or evidence of deep vein thrombosis or pulmonary embolism requiring ongoing therapeutic anticoagulation at the time of pre-conditioning.
- •Patients with active gastrointestinal bleeding.
- •Active infectious bacterial, viral disease or fungal disease (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T cell lymphotropic virus or syphilis) requiring treatment.
- •Active autoimmune disease requiring immunosuppression.
- •History of other neoplasms unless disease free for at least 2 years (adequately treated carcinoma in situ, curatively treated non-melanoma skin cancer, breast or prostate cancer on hormonal therapy are allowed).
- •Prior treatment with programmed cell death protein 1, programmed death ligand 1, or cytotoxic T lymphocyte-associated protein 4 targeted therapy, or tumour necrosis factor (TNF) receptor superfamily agonists including cluster of differentiation (CD)134 (OX40), CD27, CD137 (41BB), and CD357 (glucocorticoid induced TNF receptor family related protein) within 6 weeks prior to AUTO4 infusion.
- •Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
- •Use of rituximab (or rituximab biosimilar) within the last 6 months prior to AUTO4 infusion.
- •Patients, who in the opinion of the Investigator, may not be able to understand or comply with the safety monitoring requirements of the study.
研究组 & 干预措施
AUTO4
Experimental
Relapsed or refractory T cell non-Hodgkin Lymphoma patients
干预措施: AUTO4 (Biological)
结局指标
主要结局
The Numbers of Patients With Grade 3 to 5 Toxicity Occurring Within 60 Days of AUTO4 Infusion.
时间窗: 60 days of AUTO4 infusion
To assess the safety and tolerability of AUTO4 administration. The incidence of Grade 3-5 toxicities occurring within 60 days of AUTO4 infusion.
Frequency of Dose-limiting Toxicity (DLT) of AUTO4 Within 28 Days of AUTO4 Infusion.
时间窗: 28 days of AUTO4 infusion
To identify the recommended Phase II dose and maximum tolerated dose (MTD), if an MTD exists, of AUTO4 by monitoring the frequency of DLT of AUTO4 within 28 days of AUTO4 infusion.
次要结局
- Frequency and Severity of All Adverse Events (AEs) and Serious Adverse Events (SAEs).(24 months post treatment)
- To Assess the Overall Safety and Tolerability of AUTO4.(24 months post treatment)
- Feasibility of Generating AUTO4: Number of Patients Whose Cells Achieve Successful AUTO4 Manufacture as a Proportion of the Number of Patients Undergoing Leukapheresis.(Up to 8 weeks post leukapheresis)
- Determine the Complete Response (CR) Rate Following Treatment With AUTO4.(Up to 24 months)
- Evaluate Duration of Response (DOR) Following Treatment With AUTO4.(Up to 24 months)
- Evaluate Progression-free Survival (PFS) Following Treatment With AUTO4.(Up to 24 months)
- Evaluate Overall Survival (OS) Following Treatment With AUTO4.(Up to 24 months)
- Time to Response (PR and CR)(24 months post treatment)
- Evaluate Time to CR Following Treatment With AUTO4.(Up to 24 months)
- To Determine the Expansion and Persistence of AUTO4 Following Infusion.(Up to 24 months)
- Duration of TRBC1 Positive T Cell Aplasia.(Up to 24 months)
研究者
研究点 (5)
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