CTL-119(CTL-119) - 药物靶点：CD19_在研适应症：前体B细胞急性淋巴细胞白血病，CD19阳性B细胞急性淋巴细胞白血病，前体B细胞成淋巴细胞白血病淋巴瘤_专利_临床

概要

基本信息

药物类型

自体CAR-T

别名

Anti-CD19 CAR-T cell therapy - Novartis/University of Pennsylvania、HUCART19

+ [2]

靶点

CD19

作用机制

CD19调节剂(B淋巴细胞抗原CD19调节剂)、T淋巴细胞替代物

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病+ [2]

在研适应症

前体B细胞急性淋巴细胞白血病CD19阳性B细胞急性淋巴细胞白血病前体B细胞成淋巴细胞白血病淋巴瘤+ [2]

非在研适应症

慢性淋巴细胞白血病弥漫性大B细胞淋巴瘤小淋巴细胞淋巴瘤

原研机构

Novartis Pharma AG

在研机构

University of Pennsylvania

The Children's Hospital of Philadelphia

Novartis AG

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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序列信息

Sequence Code 119909co-stimulatory domain

Sequence Code 163267CAR construct

Sequence Code 133244

关联

7

项与 CTL-119 相关的临床试验

NCT04419909 / Not yet recruiting临床1期IIT

Retreatment With CTL019/CTL119 in Patients With Late Relapse of B-Cell Lymphomas

This research study is designed to evaluate the effects of retreatment with CTL019/CTL119 in patients with late relapse of B-cell lymphomas.

开始日期2025-05-01

申办/合作机构

University of Pennsylvania

NCT05674175 / Recruiting临床1/2期IIT

Use of Autologous Anti-CD22 CAR T Cells (CART22-65s) Co-administered With Humanized Anti-CD19 CAR T Cells (huCART19) in Children and Young Adults With Relapsed or Refractory B-ALL

This study will evaluate the safety and efficacy of administering two CAR T cell products, huCART19 and CART22-65s, in children with advanced B cell Acute Lymphoblastic Leukemia (B-ALL).

开始日期2023-01-25

申办/合作机构

The Children's Hospital of Philadelphia

[+1]

NCT03792633 / Completed临床2期IIT

Phase 2 Study of Humanized CD19-directed Chimeric Antigen Receptor-modified T Cells (huCART19) for Very High-Risk Subsets of B Cell Acute Lymphoblastic Leukemia (B-ALL)

This is a phase 2 study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia. This study is targeting pediatric and young adult patients aged 1-29 years with CD19+ B cell malignancies in newly diagnosed B-ALL patients predicted to have an exceedingly poor outcome with conventional chemotherapy, in high-risk first relapse, or and in second or greater relapse in this phase 2 trial. In addition, a second cohort will test the efficacy of huCART19 in patients with poor response to prior B cell directed engineered cell therapy.

开始日期2019-01-18

申办/合作机构

University of Pennsylvania

[+1]

100 项与 CTL-119 相关的临床结果

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100 项与 CTL-119 相关的转化医学

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100 项与 CTL-119 相关的专利（医药）

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7

项与 CTL-119 相关的文献（医药）

2024-05-14·Blood Advances

Reinfusion of CD19 CAR T cells for relapse prevention and treatment in children with acute lymphoblastic leukemia

Article

作者: DiNofia, Amanda M. ; Fraietta, Joseph A. ; June, Carl H. ; Wray, Lisa ; McGuire, Regina ; Baniewicz, Diane ; Li, Yimei ; Lawrence, Sophie ; Grupp, Stephan A. ; Devine, Kaitlin ; Hunger, Stephen P. ; Kulikovskaya, Irina ; Rheingold, Susan R. ; Callahan, Colleen ; Wertheim, Gerald B. ; Aplenc, Richard ; Leahy, Allison Barz ; Maude, Shannon L. ; Vernau, Lauren ; Liu, Hongyan ; Myers, Regina M. ; Kadauke, Stephan ; Gonzalez, Vanessa E.

AbstractRelapse after CD19-directed chimeric antigen receptor (CAR)–modified T cells remains a substantial challenge. Short CAR T-cell persistence contributes to relapse risk, necessitating novel approaches to prolong durability. CAR T-cell reinfusion (CARTr) represents a potential strategy to reduce the risk of or treat relapsed disease after initial CAR T-cell infusion (CARTi). We conducted a retrospective review of reinfusion of murine (CTL019) or humanized (huCART19) anti–CD19/4-1BB CAR T cells across 3 clinical trials or commercial tisagenlecleucel for relapse prevention (peripheral B-cell recovery [BCR] or marrow hematogones ≤6 months after CARTi), minimal residual disease (MRD) or relapse, or nonresponse to CARTi. The primary endpoint was complete response (CR) at day 28 after CARTr, defined as complete remission with B-cell aplasia. Of 262 primary treatments, 81 were followed by ≥1 reinfusion (investigational CTL019, n = 44; huCART19, n = 26; tisagenlecleucel, n = 11), representing 79 patients. Of 63 reinfusions for relapse prevention, 52% achieved CR (BCR, 15/40 [38%]; hematogones, 18/23 [78%]). Lymphodepletion was associated with response to CARTr for BCR (odds ratio [OR], 33.57; P = .015) but not hematogones (OR, 0.30; P = .291). The cumulative incidence of relapse was 29% at 24 months for CR vs 61% for nonresponse to CARTr (P = .259). For MRD/relapse, CR rate to CARTr was 50% (5/10), but 0/8 for nonresponse to CARTi. Toxicity was generally mild, with the only grade ≥3 cytokine release syndrome (n = 6) or neurotoxicity (n = 1) observed in MRD/relapse treatment. Reinfusion of CTL019/tisagenlecleucel or huCART19 is safe, may reduce relapse risk in a subset of patients, and can reinduce remission in CD19+ relapse.

2023-03-01·Blood Cancer Discovery

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy

Article

作者: Ferthio, Regina ; Koterba, Natalka ; Mansfield, Keith G. ; Carreno, Beatriz M. ; Young, Regina M. ; Miao, Fei ; Cohen, Adam D. ; Lancaster, Eric ; Plesa, Gabriela ; Wilson, Wesley V. ; Gonzalez, Vanessa E. ; Gupta, Minnal ; Linette, Gerald P. ; Hexner, Elizabeth O. ; Lacey, Simon F. ; June, Carl H. ; Bu, Dexiu ; Stadtmauer, Edward A. ; Siegel, Don L. ; Patchin, Margaret ; Four, Megan ; Vogl, Dan T. ; Nelson, Anne Marie ; Brogdon, Jennifer L. ; Kulikovskaya, Irina ; Cosey, Angela ; Garfall, Alfred L. ; Bartoszek, Robert L. ; Leskowitz, Rachel ; Waxman, Adam J. ; Chen, Fang ; Susanibar-Adaniya, Sandra P. ; Fraietta, Joseph A. ; Shea, Kim-Marie ; Brennan, Andrea ; Xu, Rong ; Milone, Michael C. ; Hwang, Wei-Ting ; Tian, Lifeng

AbstractWe conducted a phase I clinical trial of anti-BCMA chimeric antigen receptor T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later-line therapy (phase A, N = 10) or high-risk patients responding to first-line therapy (phase B, N = 20), followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade cytokine release syndrome (CRS) and only one instance of low-grade neurologic toxicity. Among 15 subjects with measurable disease, 10 exhibited partial response (PR) or better; among 26 subjects responding to prior therapy, 9 improved their response category and 4 converted to minimal residual disease (MRD)–negative complete response/stringent complete response. Early maintenance therapy was safe, feasible, and coincided in some patients with CAR T-cell reexpansion and late-onset, durable clinical response. Outcomes with CART-BCMA + huCART19 were similar to CART-BCMA alone. Collectively, our results demonstrate favorable safety, pharmacokinetics, and antimyeloma activity of dual-target CAR T-cell therapy in early lines of MM treatment.Significance:CAR T cells in early lines of MM therapy could be safer and more effective than in the advanced setting, where prior studies have focused. We evaluated the safety, pharmacokinetics, and efficacy of CAR T cells in patients with low disease burden, responding to current therapy, combined with standard maintenance therapy.This article is highlighted in the In This Issue feature, p. 101

2022-11-08·Blood Advances2区 · 医学

Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia

2区 · 医学

Article

作者: Mato, Anthony R. ; Porter, David L. ; Vides, Vanessa ; Lamontagne, Anne ; Melenhorst, J. Joseph ; Frey, Noelle V. ; June, Carl H. ; Hexner, Elizabeth O. ; Byrd, John C. ; O'Brien, Megan ; Gill, Saar ; Gladney, Whitney L. ; Siegel, Donald L. ; Brogdon, Jennifer L. ; Pequignot, Edward ; Fraietta, Joseph A. ; Levine, Bruce L. ; Metzger, Susan ; Davis, Megan M. ; Maus, Marcela V. ; Shestov, Maksim ; Lacey, Simon F. ; Schuster, Stephen J. ; Hwang, Wei-Ting ; Ruella, Marco ; Gaymon, Avery L.

AbstractIn chronic lymphocytic leukemia (CLL) patients who achieve a complete remission (CR) to anti-CD19 chimeric antigen receptor T cells (CART-19), remissions are remarkably durable. Preclinical data suggesting synergy between CART-19 and the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib prompted us to conduct a prospective single-center phase 2 trial in which we added autologous anti-CD19 humanized binding domain T cells (huCART-19) to ibrutinib in patients with CLL not in CR despite ≥6 months of ibrutinib. The primary endpoints were safety, feasibility, and achievement of a CR within 3 months. Of 20 enrolled patients, 19 received huCART-19. The median follow-up for all infused patients was 41 months (range, 0.25-58 months). Eighteen patients developed cytokine release syndrome (CRS; grade 1-2 in 15 of 18 subjects), and 5 developed neurotoxicity (grade 1-2 in 4 patients, grade 4 in 1 patient). While the 3-month CR rate among International Working Group on CLL (iwCLL)-evaluable patients was 44% (90% confidence interval [CI], 23-67%), at 12 months, 72% of patients tested had no measurable residual disease (MRD). The estimated overall and progression-free survival at 48 months were 84% and 70%, respectively. Of 15 patients with undetectable MRD at 3 or 6 months, 13 remain in ongoing CR at the last follow-up. In patients with CLL not achieving a CR despite ≥6 months of ibrutinib, adding huCART-19 mediated a high rate of deep and durable remissions. ClinicalTrials.gov number, NCT02640209.

100 项与 CTL-119 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
CD19阳性B细胞急性淋巴细胞白血病	临床2期	美国	The Children's Hospital of Philadelphia	2023-01-25
前体B细胞成淋巴细胞白血病淋巴瘤	临床2期	美国	The Children's Hospital of Philadelphia	2023-01-25
前体B细胞急性淋巴细胞白血病	临床2期	美国	University of Pennsylvania	2019-01-18
难治性成人急性淋巴细胞白血病	临床1期	美国	University of Pennsylvania	2018-09-27
多发性骨髓瘤	临床1期	美国	Novartis AG	2018-05-09
多发性骨髓瘤	临床1期	美国	University of Pennsylvania	2018-05-09
慢性淋巴细胞白血病	临床前	美国	University of Pennsylvania	2016-01-29
小淋巴细胞淋巴瘤	临床前	美国	University of Pennsylvania	2016-01-29
弥漫性大B细胞淋巴瘤	药物发现	美国	University of Pennsylvania	2014-03-25

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临床结果

适应症

分期

评价

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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


NCT02640209 (Pubmed \| Blood Adv) 人工标引	临床1期	慢性淋巴细胞白血病	19	CTL-119+Ibrutinib	(繭製廠憲衊壓壓構鏇範) = 18pts cytokine release syndrome (CRS; grade 1-2 in 15pts) and 5pts neurotoxicity (grade 1-2 in 4pts, grade 4 in 1pt) 鑰構遞襯構範窪窪鬱憲 (齋構齋艱遞膚構選糧淵 )	积极	2022-03-29