NCT04206943Unknown1 期
Phase I/ II Study of Cluster of Differentiation 19 (CD19) Specific CAR-T Cells (ISIKOK 19) in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) and Non Hodgkin Lymphoma (NHL)
Acibadem University2 个研究点 分布在 1 个国家目标入组 24 人开始时间: 2019年10月12日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Incidence of Adverse Events
研究概览
简要总结
It is a treatment that activates and strengthens the immune system against cancer. Recently, T cell receptors have been genetically rearranged by adaptive T cell therapies, which are promising in the fight against cancer, and are now able to recognize antigens on tumor cells. These modified T cell receptors are called chimeric antigen receptors. Many previous clinical studies have shown that different CAR-T cells are effective in relapse / refractory B cell cancers and NHL.
详细描述
Clinical trials of CAR-T cell therapy started at the end of 1990s. Phase I and II trials have still evaluated the efficacy and safety of CAR-T cells in hematological and solid cancers. The therapy involves drawing blood from patients and isolation of the T cells. Next, the T cells are genetically engineered in a laboratory by using virus or sleeping beauty to produce receptors on their surface named as chimeric antigen receptors. As the last step, the CAR-T cells are infused back into the patient. After infusion, it is expected that the CAR-T cells further increase in number in the patient's body and with the help of their engineered receptor to recognize and target the antigen on the surface of the cancerous cells for antitumor effect.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Been diagnosed with CD19 (+) B-Acute lymphoblastic lymphoma or CD19 (+) Non-Hodgkin Lymphoma
- •Having a measurable disease
- •Relapsed/ refractory (at least 2 cases to the ward; in relapse after autologous transplantation in NHL) disease
- •CD19 (+) expression in tumor cells by bone marrow/tissue or peripheral blood flow cytometry for relapse patients in the 3-month before the study period
- •Bone marrow relapse after allogenic stem cell transplantation and at least 6 months between CAR-T (ISIKOK-19 ©) cell infusion and stem cell transplantation
- •Philadelphia gene + B-ALL patient should have received second line treatment with tyrosine kinase inhibitor (TKI) or the usage of tyrosine kinase inhibitor (TKI) for the patient is contraindicated
- •Patient; lack of appropriate donor, complications due to previous stem cell transplantation, or rejection of stem cell transplantation as a treatment option after consultation with a physician, or lack of allogenic stem cell transplantation due to high tumor burden.
- •Lack of organ dysfunction:
- •Maximum serum creatinine value: 1.7 mg / decilitre (male patients), 1.4 mg / decilitre (female patients)
- •Liver function tests are within normal limits
- •Bilirubin <2.0 mg / decilitre
- •Central oxygen pressure in room air > 91% and no dyspnea
- •Measurement of left ventricular ejection fraction ≥45% and left ventricular systolic function ≥28% by echocardiography during screening
- •Expected survival is ≥ 3 months
- •Performance condition: Karnofsky ≥ 50%
- •Consent to oral contraceptives
- •Approve treatment
排除标准
- •Concomitant history of cardiac, hepatic, neurologic, nephrologic, psychiatric, autoimmune and additional oncological diseases affecting physiological functions
- •Life expectancy <2 months
- •Hepatitis B, Hepatitis C, Human immunodeficiency virus infection
- •Before CAR-T (ISIKOK-19 ©) cell infusion
- •Systemic steroid treatments, tyrosine kinase inhibitors, hydroxyurea, short-acting cytotoxic drugs should be stopped 72 hours before.
- •1 week ago, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate (if <25 mg / m^2), cytosine arabinoside (if <100 mg / m^2), asparaginase and intrathecal treatments should be stopped.
- •2 weeks ago, salvage treatments (chemotherapy drugs other than lymphodepletion as part of the protocol, clofarabine, cytosine arabinoside (if> 100 mg / m^2), anthracyclines, methotrexate (if ≥25 mg / m^2), drugs used for graft versus host disease, long-acting growth factors, vincristine, immunomodulatory drugs should be stopped.
- •Radiotherapy taken outside the central nervous system should be stopped 2 weeks prior.
- •Any systemic treatment with pegylated asparaginase and donor lymphocyte infusion should be stopped 4 weeks prior.
- •Anti-t cell therapies containing T cell lysis or toxic antibodies should be stopped 8 weeks before.
- •Radiotherapy for the central nervous system should be stopped 8 weeks ago.
- •Less than 3 months after stem cell transplantation
- •Below 60% in tissue biopsies and / or CD19 expression in tumor cells by flow cytometric analysis in bone marrow is below 85%
- •Allergic to drugs that are used at any stage of treatment
- •Having received experimental drug treatment in the last month
- •Previously entered a cellular therapy and / or a gene therapy program
- •Disapproval of the storage of tissues and cells
- •Isolated disease that occurs outside the bone
- •A genetic disease associated with concomitant bone marrow failure
- •Active Grade 2-4 acute or diffuse chronic graft versus host disease
- •Being pregnant or breastfeeding
- •Disapproval the treatment
- •Patients with slow CAR-T cell expansion (the cell number is not doubled in 48 hours) and with less than 10% expression of CAR-T cells during production, < 60% cytotoxicity results in in-vitro study (i.e, patients whose product is inappropriate)
结局指标
主要结局
Incidence of Adverse Events
时间窗: 6 Months
Type, frequency and severity of adverse events (AEs) and laboratory abnormalities.
次要结局
- Complete Remission Rate(3 Months)
- Total Response Rate(3 Months)
- Duration of Remission (DOR)(6 Months)
- Relapse Free Survival (RFS)(6 Months)
- Progression Free Survival(6 Months)
- Event-Free Survival (EFS)(6 Months)
- Overall Survival(6 Months)
- Duration to maximum response(6 Months)
- The impact of baseline tumor burden on response(6 Months)
- The relationship between CRS/CRES efficiency(6 Months)
- The relationship between the total response and Car-T Cell persistence(6 Months)
- The relationship between Car-T Cell product content and responses(6 Months)
- Car-T cell proliferation capability(6 months)
- The relationship between MRD grade and clinical response(6 Months)
- The relationship between the incidence of immune response to Car-T cells and the persistence of Car-T cell(6 Months)
研究者
研究点 (2)
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