This phase II trial compares the safety, side effects and effectiveness of reduced dose radiation therapy to standard of care dose radiation in treating patients with indolent non-Hodgkin lymphoma. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Standard of care radiation treatment for indolent non-Hodgkin lymphoma is usually delivered in 12 treatments. Studies have shown indolent lymphoma to be sensitive to radiation treatment, however, larger doses have higher rates of toxicities. A reduced radiation dose may be safe, tolerable and/or effective compared to standard of care radiation dose in treating patients with indolent non-Hodgkin lymphoma.

开始日期2024-05-15

申办/合作机构

Mayo Clinic

NCT04635683 / Withdrawn临床1期IIT

A Phase I Trial of Lenalidomide, Umbralisib and Ublituximab in Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

This phase I trial studies the safety and how effective the combination of ublituximab, umbralisib, and lenalidomide is in certain types of indolent (slow-growing) non-Hodgkin's lymphoma or mantle cell lymphoma. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of non-Hodgkin's lymphoma by blocking blood flow to the cancer. Umbralisib is designed to block a protein called PI3 kinase in order to stop cancer growth and cause changes in the immune system that may allow the immune system to better act against cancer cells. Ublituximab is an antibody that attaches to the lymphoma cells and triggers immune reactions that may result in the death of the targeted lymphoma cells.

开始日期2022-09-30

申办/合作机构

Ohio State University Comprehensive Cancer Center

NCT04836832 / Withdrawn临床1期IIT

A Phase Ib/II Study of Duvelisib and Acalabrutinib in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (DUAL Trial)

This phase Ib/II trial studies the side effects of acalabrutinib and duvelisib and how well they work in treating patients with indolent non-Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Acalabrutinib inhibits a signaling molecule called Bruton tyrosine kinase and blocks cancer cell proliferation, growth, and survival. Duvelisib is designed to block a protein called PI3 kinase in order to stop cancer growth and cause changes in the immune system that may allow the immune system to better act against cancer cells. Giving acalabrutinib and duvelisib together may work better to block cancer growth than therapy of either drug alone.

开始日期2022-07-01

申办/合作机构

Ohio State University Comprehensive Cancer Center

100 项与难治性惰性非霍奇金淋巴瘤相关的临床结果

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0 项与难治性惰性非霍奇金淋巴瘤相关的专利（医药）

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项与难治性惰性非霍奇金淋巴瘤相关的文献（医药）

2024-08-01·eClinicalMedicine

Safety and activity of lenalidomide in combination with obinutuzumab in patients with relapsed indolent non-Hodgkin lymphoma: a single group, open-label, phase 1/2 trial

Article

作者: Feng, Lei ; Chin, Collin K ; Hagemeister, Fredrick B. ; Hagemeister, Fredrick B ; Gurumurthi, Ashwath ; Fayad, Luis E. ; Strati, Paolo ; Steiner, Raphael E ; Fowler, Nathan H ; Neelapu, Sattva S. ; Nastoupil, Loretta J ; Steiner, Raphael E. ; Flowers, Christopher R ; Obi, Chizobam ; Neelapu, Sattva S ; Nastoupil, Loretta J. ; Chin, Collin K. ; Arafat, Janine ; Flowers, Christopher R. ; Nair, Ranjit ; Westin, Jason R ; Fayad, Luis E ; Westin, Jason R. ; Fowler, Nathan H.

BackgroundRituximab and lenalidomide is a preferred option for relapsed indolent B cell non-Hodgkin lymphoma. Obinutuzumab may be a superior combination partner with lenalidomide given enhanced antibody dependent cellular cytotoxicity and phagocytosis compared to rituximab. Our aim was to determine the recommended phase 2 dose, safety, and activity of lenalidomide in combination with fixed dose of obinutuzumab in relapsed and refractory indolent B cell non-Hodgkin lymphoma.MethodsIn this single-arm, open-label, phase 1/2 trial, we enrolled patients with relapsed or refractory WHO Grade 1-3A follicular lymphoma, marginal zone lymphoma and small lymphocytic lymphoma and adequate performance status (ECOG 0-2) at the MD Anderson Cancer Center. We excluded patients with evidence of ongoing transformation to aggressive lymphoma. During phase 1, 1000 mg intravenous obinutuzumab was administered with three predefined levels of oral lenalidomide in a 3 + 3 dose escalation design to establish lenalidomide 20 mg as the recommended phase 2 dose. During phase 2, patients received induction therapy with six 28-day cycles of lenalidomide 20 mg with intravenous obinutuzumab 1000 mg. In accordance with our prior experience with lenalidomide plus rituximab, patients who were responding to the combination could receive up to 6 additional cycles (up to 12 cycles in total) of combination therapy. Dosing of obinutuzumab was continued in all responding patients after cycle 6 every 2 months for a total of 30 months from the start of therapy. The decision of number of cycles of combination therapy beyond 6 was at discretion of the investigator and was included to allow individualisation of therapy to maximise response while minimising exposure. The co-primary objectives were to evaluate the safety and overall response, defined as the proportion of patients who achieved a complete or partial response in relapsed and refractory indolent non-Hodgkin lymphoma at the end of induction therapy, according to Cheson and colleagues (2007 criteria). The secondary endpoints were complete response after induction therapy and time to event endpoints including time to progression, progression free survival, and overall survival. Analyses were intent to treat in the efficacy cohort and per-treated in the safety population in all patients who received at least one dose of either investigational agent. This trial is registered with ClinicalTrials.gov, NCT01995669.FindingsBetween June 03, 2014, and 07 March 2019, we completed planned enrolment, and 66 patients started therapy including 9 patients in phase 1 and 57 patients in phase 2. All patients were evaluated for safety and the 60 patients treated at the recommended phase 2 dose of lenalidomide 20 mg were evaluable for activity. Grade 3-4 haematological toxicities included neutropenia 21% (14/66) and thrombocytopenia 11% (7/66) with no cases of febrile neutropenia. Grade 3-4 non-haematological toxicities included lung infection 8% (5/66), fatigue 8% (5/66) and rash 6% (4/66). By Cheson 2007 criteria, 90% (54/60, 95% CI: 79-96) achieved an overall response at the end of induction meeting the prespecified activity endpoint. Complete responses were seen in 33% (20/60, 95% CI: 22-47) at the end of induction. Median progression free survival, time to progression and overall survival have not been reached after median follow-up of 41.7 months. Estimated 4-year progression free survival rates were 55% (95% CI: 42-73), time to progression of 56% (95% CI: 43-74) and overall survival of 84% (95% CI: 74-95).InterpretationOur findings suggest that oral lenalidomide with obinutuzumab is safe and highly active in patients with relapsed and refractory indolent B cell non-Hodgkin lymphoma and is associated with prolonged remission duration. The study is limited by the lack of a control arm leading to cross-trial comparisons to evaluate activity. Future randomised trials comparing this regime to rituximab and lenalidomide are warranted.FundingGenentech and an MD Anderson Core grant.

2024-08-01·eClinicalMedicine

Safety and activity of lenalidomide in combination with obinutuzumab in patients with relapsed indolent non-Hodgkin lymphoma: a single group, open-label, phase 1/2 trial

Article

作者: Feng, Lei ; Chin, Collin K ; Hagemeister, Fredrick B ; Gurumurthi, Ashwath ; Strati, Paolo ; Fowler, Nathan H ; Steiner, Raphael E ; Nastoupil, Loretta J ; Flowers, Christopher R ; Obi, Chizobam ; Neelapu, Sattva S ; Westin, Jason R ; Arafat, Janine ; Nair, Ranjit ; Fayad, Luis E

2024-02-08·Blood

Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5)

Article

作者: Neelapu, Sattva S ; Ulrickson, Matthew ; Bachy, Emmanuel ; Beygi, Sara ; Rosenblatt, Joseph ; Lui, Christine ; Casulo, Carla ; Khanal, Rashmi ; Jacobson, Caron A ; Yakoub-Agha, Ibrahim ; Korn, Ronald ; Jung, A Scott ; Maloney, David G ; Munshi, Pashna N ; Leslie, Lori A ; Wulff, Jacob ; Sehgal, Alison R ; Shen, Rhine ; Poddar, Soumya ; Chavez, Julio C ; Reshef, Ran ; Oluwole, Olalekan O ; Peng, Weixin ; de Vos, Sven ; Epperla, Narendranath ; Miao, Harry

AbstractAxicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R/R indolent non-Hodgkin lymphoma (iNHL; N = 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.5 months), the overall response rate (ORR) was 92% (complete response rate, 74%). Here, we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ≥2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2 × 106 CAR T cells per kg). The primary end point was ORR, assessed in this analysis by investigators in all enrolled patients (intent-to-treat). After median follow-up of 41.7 months in FL (n = 127) and 31.8 months in MZL (n = 31), ORR was comparable with that of the primary analysis (FL, 94%; MZL, 77%). Median progression-free survival was 40.2 months in FL and not reached in MZL. Medians of overall survival were not reached in either disease type. Grade ≥3 adverse events of interest that occurred after the prior analyses were largely in recently treated patients. Clinical and pharmacokinetic outcomes correlated negatively with recent exposure to bendamustine and high metabolic tumor volume. After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond 2 years, and manageable safety in patients with R/R iNHL. The ZUMA-5 study was registered at www.clinicaltrials.gov as #NCT03105336.

项与难治性惰性非霍奇金淋巴瘤相关的新闻（医药）

2024-09-24

·药时代

吉利德退出，复星医药实现100%控权！

2024年9月13日，复星医药宣布，其控股子公司复星医药产业拟现金出资2700万美元受让Kite Pharma持有的复星凯特50%的股权。转让完成后，复星医药将全资持股，复星凯特也将迎来更名，新公司名拟定为复星凯瑞。签订《股权转让协议》的同日，复星凯特与Kite就原许可协议进行重新修订。根据修订后内容，复星凯特获得Kite许可区域（中国内地、香港和澳门）及领域（癌症治疗领域）内独家开发、生产及商业化奕凯达及Brexu-Cel（复星凯特在研项目FKC889）的权利。 Kite将获得药物销售额的7%~13%的分层特许权使用费。另对于复星凯特的管线资产，Kite有权获得2%~4%的销售特许权使用费。此外，复星医药除股权受让的2700万美金外，还将另增资1000万美元，强化复兴凯特在生物医药领域的布局。据悉，包括阿基仑赛注射液在内的四款CAR-T疗法均在即将开展的2024年国家医保谈判中递交了申请信息。 Kite、复兴医药、吉利德 2017年是CAR-T疗法元年。当年7月，诺华的CAR-T疗法产品tisagenlecleucel在ODAC会议上获10名专家咨询委员会成员的一致推荐。一个月后，即2017年8月30日，该产品被FDA正式批准上市，用于治疗 25 岁以下难治性/二次/更晚复发的 B 细胞前体急性淋巴细胞白血病患者，商品名Kymriah。据悉，这是FDA批准的首款CAR-T疗法。 Kite是CAR-T研发领域的领军企业之一。2016年年末，Kite就宣布其研发的CAR-T疗法阿基仑赛注射液（axicabtagene ciloleucel，KTE-C19）的BLA申请被FDA受理，PDUFA日期2017年11月29日，有望成为FDA批准的第一个治疗非霍奇金淋巴瘤的CAR-T产疗法。 2017年初，复星医药通过其全资子公司与Kite成立中外合营企业——复兴凯特。其中，复星医药现金出资2000万美元，Kite以产品及专有技术独家使用权作价2000万美元，双方各占合营企业50%股权。根据当时协议条款，复星医药将另向合营企业支付4000万美元用于支付相关专利和技术费用，合营企业将根据研发进展及市场情况向Kite支付3500万美元的里程碑及就阿基仑赛注射液产品支付销售提成。也就是说，在当时的这笔合作中，复星医药承诺金额最高达9500美元。吉利德与Kite的收购交易也是在2017年。2017年8月28日，吉利德/Kite共同宣布，吉利德将以每股118美元的现金价格（总值约119亿美元）收购Kite。收购行为与吉利德当时所面临的困境有关，当时其丙肝产品销售额萎缩，艾滋病业务遭遇挑战，管线产品储备不足。但根据当时吉利德H1财报，其账面资金充足，有大约360亿美元现金。因此，收购其实是吉利德解决当时困境最直接的方法。中外陆续上市在吉利德宣布收购Kite的消息后2个月，即2017年10月18日，FDA批准阿基仑赛注射液上市，商品名Yescarta。目前，吉利德的细胞疗法板块共两款上市CAR-T产品，分别为Yescarta和Tecartus，均来自Kite。其中，Tecartus与2020年首次被FDA批准上市。根据吉利德2024H1财报信息，两款CAR-T产品在过去的半年时间里共营收10.01亿美元，其中Yescarta贡献大部分，约7.94亿美元。 Yescarta是目前全球范围内所有上市CAR-T疗法中年营收唯一突破10亿美元的产品。自复兴医药通过合资共建公司将这款产品引入中国后，该产品已于2021年6月22日被NMPA批准上市，商品名奕凯达，是中国首个获批上市的CAR-T疗法，用于治疗既往接受二线或以上系统性治疗后复发或难治性大B细胞淋巴瘤成人患者。2023年6月26日，阿基仑赛注射液再被NMPA批准用于二线复发成人大B细胞淋巴瘤的治疗。据悉，目前奕凯达已治疗超过600位复发/难治性大B细胞淋巴瘤患者。根据复星医药官方消息，在全资控股后，将进一步提高产品可及性。此外，阿基仑赛注射液的第三项适应症的临床试验申请已在中国境内获批，目标人群为复发/难治性惰性非霍奇金淋巴瘤的成人患者。目前该项适应症于中国境内处于桥接临床试验阶段。小结近期，除Kite外，还有其他几家公司拆分了中国业务，将权益留给了本地制药商。其中包括： 2024年8 月 31 日，北京天坛生物制品股份有限公司发布《关于成都蓉生收购武汉中原瑞德生物制品有限责任公司100% 股权的公告》，宣布其控股子公司成都蓉生药业有限责任公司拟以 1.85 亿美元总金额收购杰特贝林（亚太区）有限公司（CSL BEHRING ASIA PACIFIC LIMITED）全资子公司武汉中原瑞德生物制品有限责任公司 100% 股权。 2024年8月26日，优时比（UCB）宣布将以 6.8 亿美元的价格将其在中国成熟业务（包括5款药物和珠海生产基地）出售给康桥资本和阿布扎比的投资公司Mubadala。参考资料： 1.各公司官网 2.其他公开资料封面图来源：pixabay 版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 药品上市被拒，Vanda再次破防！ 20周减重最高达21%！玛仕度肽16mg减重疗效更上一层楼，研究结果亮相EASD！ 2024年拉斯克奖揭晓，陈志坚获基础医学奖点击查看更多精彩！

细胞疗法免疫疗法并购上市批准财报

2024-09-20

·药渡Daily

更名为复星凯瑞，复星凯特将独占Yescarta

根据行业媒体报道，日前吉利德旗下的Kite Pharma将出售其在复星凯特公司的50%股份。另在9月13日，复星向上海证券交易所提交的文件中也得以透露：计划支付2700万美元收购Kite Pharma的股份。这笔交易将使复星在中国完全控制Yescarta和Brexu-Cel。 Yescarta Yescarta是中国首个获批的CD19靶向的CAR-T疗法，于2021年6月获批用于治疗2线或以上系统治疗后的复发/难治性大B细胞淋巴瘤患者。2023年6月，Yescarta用于治疗1线免疫化疗无效或在1线免疫化疗后12个月内复发的成人大B细胞淋巴瘤，获NMPA附条件批准。目前，Yescarta的第3项适应症的临床试验申请已在中国境内获批，目标人群为复发/难治性惰性非霍奇金淋巴瘤的成人患者。目前该项适应症于中国境内处于桥接临床试验阶段。 Brexu-Cel Brexu-Cel同为靶向CD19的CAR-T疗法，2021年获FDA批准用于治疗复发/难治性B细胞前体急性淋巴细胞白血病成人患者。国内曾迎来CAR-T疗法的上市井喷。根据药渡数据，目前已有6款CAR-T疗法上市，分别为复星凯特的阿基仑赛注射液（Yescarta）、药明巨诺的瑞基奥仑赛注射液、驯鹿生物/信达生物的伊基奥仑赛注射液、合源生物的纳基奥仑赛注射液、科济生物/华东医药的泽沃基奥仑赛注射液、以及传奇生物的西达基奥仑赛注射液。因此，复星凯特在血癌领域面临激烈的竞争。2023年，复星凯特的收入为2.42亿元；相比之下，同靶向CD19的竞争对手瑞基奥仑赛注射液去年的销售额为1.74亿美元，且今年8月又斩获了新的适应症——用于治疗成人复发或难治性套细胞淋巴瘤。复星凯特的先发优势正在减小。 Yescarta在中国的价格为120万元人民币。尽管在同类产品中，不算是高价，但对于大多数中国家庭来说，这个价格仍然是天文数据。据悉，自2016年推出以来，Yescarta已经在中国治疗了700多名大B细胞淋巴瘤患者。 CAR-T疗法的高价使得人群寻求医保之外的支付覆盖。为了帮助获取，复星凯特多年来探索了商业保险覆盖，包括上海政府设计的补充保险计划。根据公司的说法，这些政策能够覆盖药品成本的高达42%。此外，在1月份，复星凯特与中国医药集团的子公司合作推出了基于结果的支付计划，如果Yescarta在三个月内没有诱导完全反应，将退还患者自付成本的一半。截至目前，复星凯特已在全国28个省区市建立170多家Yescarta高标准治疗中心，并推动Yescarta纳入超过110款城市惠民保项目以及超过80款商业健康保险项目，让细胞治疗创新疗法进一步惠及更多患者，帮助更多患者重拾生存的希望。为了在2017年初组建中国合资企业，复星向Kite提供了4000万美元的首付款，并承诺为Yescarta在中国的权利支付3500万美元的里程碑款项，外加为新公司提供2000万美元的初始资金。当时，合资企业有选择权获得Kite的其他候选药物，包括TCR疗法 KITE-439和KITE-718，这两种疗法后来都被Kite终止。此次全资控股后，复星凯特拟更名为复星凯瑞；并且复星表示将向该公司额外投资1000万美元。参考资料 FIERCE PHARMA 复星凯特官网

细胞疗法免疫疗法并购临床研究临床结果

2024-09-15

·同写意

复星医药锚定创新加码优势领域，全资控股复星凯特深耕细胞疗法

细胞疗法免疫疗法财报上市批准