ADMINISTRATION OF MOST CLOSELY MATCHED THIRD PARTY RAPIDLY GENERATED LMP, BARF1 and EBNA1 SPECIFIC CYTOTOXIC T-LYMPHOCYTES TO PATIENTS WITH EBV-POSITIVE LYMPHOMA AND OTHER EBV-POSITIVE MALIGNANCIES

The subject has a type of cancer or lymph gland disease associated with a virus called Epstein Barr Virus (EBV), which has come back, is at risk of coming back, or has not gone away after standard treatments. This research study uses special immune system cells called LMP, BARF-1 and EBNA1- specific cytotoxic T lymphocytes (MABEL CTLs).
Some patients with Lymphoma (such as Hodgkin (HD) or non-Hodgkin Lymphoma (NHL)), T/NK-lymphoproliferative disease, or CAEBV, or solid tumors such as nasopharyngeal carcinoma (NPC), smooth muscle tumors, and leiomyosarcomas show signs of a virus called EBV before or at the time of their diagnosis. EBV causes mononucleosis or glandular fever ("mono" or the "kissing disease"). EBV is found in the cancer cells of up to half the patients with HD and NHL, suggesting that it may play a role in causing Lymphoma. The cancer cells (in lymphoma) and some immune system cells (in CAEBV) infected by EBV are able to hide from the body's immune system and escape destruction. EBV is also found in the majority of NPC and smooth muscle tumors, and some leiomyosarcomas. We want to see if special white blood cells (MABEL CTLs) that have been trained to kill EBV infected cells can survive in your blood and affect the tumor.
In previous studies, EBV CTLs were generated from the blood of the patient, which was often difficult if the patient had recently received chemotherapy. Also, it took up to 1-2 months to make the cells, which is not practical when a patient needs more urgent treatment. To address these issues, the MABEL CTLs were made in the lab in a simpler, faster, and safer way. The MABEL CTLs will still see LMP proteins but also two other EBV proteins called EBNA-1 and BARF. To ensure these cells are available for use in patients in urgent clinical need, we have generated MABEL CTLs from the blood of healthy donors and created a bank of these cells, which are frozen until ready for use. We have previously successfully used frozen T cells from healthy donors to treat EBV lymphoma and virus infections and we now have improved our production method to make it faster.
In this study, we want to find out if we can use banked MABEL CTLs to treat HD, NHL, T/NK-lymphoproliferative disease, CAEBV, NPC, smooth muscle tumors or leiomyosarcoma. We will search the bank to find a MABEL CTL line that is a partial match with the subject.
MABEL CTLs are investigational and not approved by the Food and Drug Administration.

开始日期2015-02-01

申办/合作机构

Baylor College of Medicine

[+2]

NCT02578641

/ Completed临床3期

A Multicentre, Randomized, Open-Label, Phase III Clinical Trial Of Gemcitabine And Carboplatin Followed By Epstein-Barr Virus-Specific Autologous Cytotoxic T Lymphocytes Versus Gemcitabine And Carboplatin As First Line Treatment For Advanced Nasopharyngeal Carcinoma(NPC) Patients

This study is a multi-center, randomized, open label, Phase III clinical trial for advanced Nasopharyngeal Carcinoma(NPC) Patients.
Drugs used in chemotherapy, such as gemcitabine and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving an infusion of a person's cytotoxic T cells (CTL) that have been treated in the laboratory may help the body build an effective immune response to kill tumor cells. Giving combination chemotherapy together with laboratory-treated T cells may kill more tumor cells. This Phase III trial is to assess if combined gemcitabine-carboplatin (GC) followed by adoptive T-cell therapy would improve clinical outcome for patients with advanced nasopharyngeal carcinoma (NPC). It is also the world's first, and largest, Phase 3 T-cell therapy cancer trial ever conducted, and enrollment is ongoing for 330 patients from 30 hospital centers across Asia and the United States.
This clinical trial is conducted on the back of a successful Phase 2 NPC trial involving 38 patients at the National Cancer Centre, Singapore. This trial produced the best published 2-year (62.9%), and median overall survival (OS) data (29.9 months) in 35 patients with advanced NPC who received autologous EBV-specific CTL. Kindly see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978790/ for the Phase 2 publication titled "Adoptive T-cell Transfer and Chemotherapy in the First line treatment of Metastatic and/or Locally Recurrent Nasopharyngeal Carcinoma".

开始日期2014-07-01

申办/合作机构

Tessa Therapeutics Ltd

NCT00058773

/ Terminated临床1期IIT

Administration of Autologous Neomycin Resistant Gene Marked EBV Specific Cytotoxic T-Lymphocytes as Therapy for Patients Receiving Autologous Bone Marrow Transplant for Relapsed EBV-Positive Lymphoma.

Subjects have a type of lymph gland cancer called Hodgkin or non-Hodgkin Lymphoma, which has come back or not gone away after treatment, including the best treatment we know for relapsed Lymphoma. We are asking subjects to volunteer to be in a research study using Epstein Barr virus (EBV) specific cytotoxic T lymphocytes, a new experimental therapy. This therapy has never been used in patients with Hodgkin disease or this type of non-Hodgkin Lymphoma but it has been used successfully in children with other types of blood cancer caused by EBV after bone marrow transplantation.
Some patients with Hodgkin disease or non-Hodgkin Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis of Lymphoma. EBV is often found in the cancer cells suggesting that it may play a role in causing Lymphoma. The cancer cells infected by EBV are very clever because they are able to hide from the body's immune system and escape destruction. We want to see if we can grow special white blood cells, called T cells, that have been trained to kill EBV infected cells and give them back to subjects.

开始日期1996-01-01

申办/合作机构

Baylor College of Medicine

[+2]

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项与 TT-10x 相关的文献（医药）

2024-12-01·Annals of Oncology

Gemcitabine, carboplatin, and Epstein–Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial

Article

作者: Horak, I ; Algazi, A ; Algazi, A. ; Samol, J ; Colevas, A.D. ; Wang, H-M ; Hsieh, C.Y. ; Ang, M K ; Yang, M.-H. ; Lertbutsayanukul, C ; Ding, C ; Ho, K F ; Samol, J. ; Wirasorn, K. ; Chitapanarux, I. ; Ong, W S ; Horak, I. ; Ho, G.F. ; Sirachainan, E ; Ho, K.F. ; Wang, W-W ; Nadler, E. ; Myo, A ; Brenner, M.K. ; Toh, H.C. ; Wang, W.-W. ; Hong, R-L ; Ang, S F ; Liu, Y C ; Colevas, A D ; Toh, H C ; Brenner, M K ; Liu, Y.C. ; Yang, M-H ; Chitapanarux, I ; Wirth, L.J. ; Sirachainan, E. ; Tan, S.H. ; Low, S.H.J. ; Ong, W.S. ; Low, S H J ; Hasbullah, H.H. ; Lulla, P ; Hasbullah, H H ; Myo, A. ; Wirth, L J ; Hsieh, C Y ; Wirasorn, K ; Tan, S H ; Ho, G F ; Nadler, E ; Wang, H.-M. ; Hong, R.-L. ; Lulla, P. ; Tho, L.M. ; Lertbutsayanukul, C. ; Ang, S.F. ; Ding, C. ; Tho, L M ; Ang, M.K.

BACKGROUNDEpstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment.PATIENTS AND METHODSThis multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety.CLINICALTRIALSgov identifier: NCT02578641.RESULTSA total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL.CONCLUSIONSGC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

2022-08-01·Zhongguo shi yan xue ye xue za zhi

[Clinical Analysis of Post-Transplant Lymphoproliferative Disorder after Hematopoietic Stem Cell Transplantation in Severe Aplastic Anemia Patients].

Article

作者: Xue, Mei ; Li, Sheng ; Zheng, Xiao-Li ; Yan, Hong-Min ; Zhu, Ling ; Liu, Jing ; Wang, Heng-Xiang ; Ding, Li ; Han, Dong-Mei

题目重型再生障碍性贫血患者造血干细胞移植治疗后淋巴组织增殖性疾病的临床分析.目的分析重型再生障碍性贫血(SAA)患者造血干细胞移植（HSCT）后淋巴组织增殖性疾病(PTLD)的临床特征,以提高对PTLD的诊疗水平.方法回顾分析2010年9月至2017年9月在单中心行HSCT的192例SAA患者的临床资料，分析PTLD的有效预警和治疗方法。本组患者预处理方案中均含有ATG并接受间充质干细胞（MSC）输注.结果192例SAA患者HSCT移植后有14例并发了EBV+ PTLD，总体发生率为7.29%，其中临床诊断5例，病理诊断9例，移植后PTLD发生中位时间72(35-168)d,所有PTLD均发生了EBV感染，且EBV高载量大于1×10⁴copies/ml（P<0.01）。年龄≤12岁和＞12岁患者分别有11.11%和2.38%发生PTLD（P<0.01）。单因素及多因素分析结果显示,EBV感染、≤12岁患者、非血缘HSCT中HLA配型不相合供者移植及发生II度以上aGVHD均为PTLD高危因素（P<0.05）。监测发现EBV>10⁴ copies/ml时,减停免疫抑制剂(RIS)和利妥昔单抗(RTX)抢先治疗有效，疗效不佳者及时联合化疗及EBV-CTL治疗后所有患者PTLD得到控制，治疗有效率100%。随访中位时间为65（62-115）个月，除1例患者在PTLD控制后7个月时死于脑出血外，余下患者均长期生存，总体生存率为92.85.结论SAA患者接受预处理含有ATG和MSC的HSCT后PTLD发生与EBV高拷贝密切相关，年龄≤12岁儿童、非血缘HSCT中供者为HLA不全相合的移植及合并有II度以上aGVHD者移植后PTLD高发； RIS/RTX抢先治疗有效，疗效不佳患者及时应用CTL及联合化疗是控制病情有效及重要方法.

2021-12-01·Transplant International2区 · 医学

EBV‐specific cytotoxic T lymphocytes for refractory EBV‐associated post‐transplant lymphoproliferative disorder in solid organ transplant recipients: a systematic review

2区 · 医学

Review

作者: Zhan, Hao‐Su ; Liu, Jing‐Yi ; Sun, Li‐Ying ; Wei, Lin ; Zhang, Jin‐Ming

The use of Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) in adoptive immunotherapy in hematopoietic stem cell transplantation (HSCT) patients with post-transplantation lymphoproliferative disorder (PTLD) has demonstrated safety and effectiveness. EBV-CTLs might also be the effective treatment of refractory PTLD of solid organ transplantation (SOT) recipients. Two independent assessors searched Pubmed, Embase, Cochrane Library, and Web of Science from their inception to November 2020. Eleven studies with 76 patients (42, 55% male) were included. We extracted the data and completed the quality assessments. Most of the studies were from Europe and the USA. Liver and kidney transplantation accounted for most of the transplant types. Thirty-five (46.1%) patients were diagnosed with monomorphic PTLD, and B lymphocyte type was the most common. All the patients received primary treatment for PTLD while it was ineffective. CTLs included autologous EBV-CTLs (15/76, 22%) and HLA-matched third-party EBV-CTLs (61/76, 78%). The response rate for EBV-CTL treatment of refractory PTLD was 66%. Of 50 patients, 36 achieved complete remission and 14 achieved partial remission. EBV-DNA level decreased in 39 patients. Adverse reactions were rare and mild. We conclude that adoptive therapy with EBV-specific CTLs is safe, well-tolerated, and effective in PTLD.

100 项与 TT-10x 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
晚期鼻咽癌	药物发现	马来西亚	Tessa Therapeutics Ltd	2014-07-01
晚期鼻咽癌	药物发现	中国台湾	Tessa Therapeutics Ltd	2014-07-01
晚期鼻咽癌	药物发现	新加坡	Tessa Therapeutics Ltd	2014-07-01
晚期鼻咽癌	药物发现	泰国	Tessa Therapeutics Ltd	2014-07-01
晚期鼻咽癌	药物发现	美国	Tessa Therapeutics Ltd	2014-07-01
鼻咽癌	药物发现	新加坡	Tessa Therapeutics Ltd	2014-07-01
鼻咽癌	药物发现	泰国	Tessa Therapeutics Ltd	2014-07-01
鼻咽癌	药物发现	马来西亚	Tessa Therapeutics Ltd	2014-07-01
鼻咽癌	药物发现	中国台湾	Tessa Therapeutics Ltd	2014-07-01
鼻咽癌	药物发现	美国	Tessa Therapeutics Ltd	2014-07-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02578641 (VANCE, Pubmed \| Ann Oncol) 人工标引	临床3期	鼻咽癌一线	330	Gemcitabine ancarboplatinin EBV-CTLEBV-CTL	(廠顧繭範淵膚製艱獵衊) = 鹽鑰衊範鏇鏇選觸網衊蓋簾鬱艱遞簾築齋膚蓋 (鹹衊蓋簾觸鏇鑰淵壓鑰 )	不佳	2024-09-01
				Gemcitabine carboplatinatin (GC)	(廠顧繭範淵膚製艱獵衊) = 糧膚願選壓構衊築衊獵蓋簾鬱艱遞簾築齋膚蓋 (鹹衊蓋簾觸鏇鑰淵壓鑰 )