Cytomegalovirus peptide vaccine(City of Hope National Medical Center)(Cytomegalovirus peptide vaccine(City of Hope National Medical Center)) - 在研适应症：成人急性淋巴细胞白血病，成人急性髓性白血病，淋巴母细胞淋巴瘤_专利_临床

概要

基本信息

药物类型

合成肽疫苗、预防性疫苗

别名

CMV fusion peptide vaccines、CMVPepVax、CMVpp65-A*0201 peptide vaccine

+ [1]

靶点-

作用方式

刺激剂

作用机制

免疫刺激剂

治疗领域

肿瘤免疫系统疾病感染+ [3]

在研适应症

成人急性淋巴细胞白血病成人急性髓性白血病淋巴母细胞淋巴瘤+ [9]

非在研适应症

癌前状态

原研机构

City of Hope National Medical Center

在研机构

National Cancer Institute

City of Hope National Medical Center

非在研机构

University of Minnesota

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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结构/序列

Sequence Code 1120173650

关联

2

项与 Cytomegalovirus peptide vaccine(City of Hope National Medical Center) 相关的临床试验

NCT02396134

/ Completed临床2期IIT

A Phase II Randomized, Placebo-Controlled, Multicenter Trial to Evaluate Protective Function of an Optimized Dose of CMVPepVax in Recipients of an Allogeneic Hematopoietic Stem Cell Transplant

This randomized phase II trial studies how well vaccine therapy works in reducing the frequency of cytomegalovirus severe infections (events) in patients with hematologic malignancies undergoing donor stem cell transplant. Vaccines made from a peptide may help the body build an effective immune response and may reduce cytomegalovirus events after donor stem cell transplant.

开始日期2015-05-21

申办/合作机构

City of Hope National Medical Center

[+1]

NCT00712634

/ Completed临床1期IIT

A Phase I Dose Escalation Study of Lipopeptide Vaccines With Activity Against Human Cytomegalovirus

RATIONALE: Vaccines may help the body build an effective immune response against cytomegalovirus.
PURPOSE: This randomized phase I trial is studying the side effects and best dose of cytomegalovirus vaccine in healthy participants.

开始日期1997-11-01

申办/合作机构

City of Hope National Medical Center

[+1]

100 项与 Cytomegalovirus peptide vaccine(City of Hope National Medical Center) 相关的临床结果

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100 项与 Cytomegalovirus peptide vaccine(City of Hope National Medical Center) 相关的转化医学

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100 项与 Cytomegalovirus peptide vaccine(City of Hope National Medical Center) 相关的专利（医药）

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3

项与 Cytomegalovirus peptide vaccine(City of Hope National Medical Center) 相关的文献（医药）

2019-04-01·Biology of Blood and Marrow Transplantation2区 · 医学

Rapid Acquisition of Cytomegalovirus-Specific T Cells with a Differentiated Phenotype, in Nonviremic Hematopoietic Stem Transplant Recipients Vaccinated with CMVPepVax

2区 · 医学

Article

作者: Longmate, Jeffrey ; Zhou, Qiao ; La Rosa, Corinna ; Aldoss, Ibrahim ; Hardwick, Nicola ; Diamond, Don J ; Kaltcheva, Teodora ; Nakamura, Ryotaro ; Lingaraju, Chetan Raj

Early cytomegalovirus (CMV) reactivation remains a significant cause of morbidity and mortality in allogeneic hematopoietic cell transplant (HCT) recipients. CMVPepVax is an investigational peptide vaccine designed to control CMV infection in HCT recipients seropositive for CMV by stimulating the expansion of T cell subsets that target the CMV tegument protein pp65. In a randomized Phase Ib pilot trial (ClinicalTrials.gov NCT01588015), two injections of CMVPepVax (at days 28 and 56 post-HCT) demonstrated safety, immunogenicity, increased relapse-free survival, and reduced CMV reactivation and use of antivirals. In the present study, we assessed the phenotypes and time courses of the pp65-specific CD8 T cell subsets that expanded in response to CMVPepVax vaccination. The functionality and antiviral role of CMV-specific T cells have been linked to immune reconstitution profiles characterized predominantly by differentiated effector memory T (TEM) subsets that have lost membrane expression of the costimulatory molecule CD28 and often reexpress the RA isoform of CD45 (TEMRA). Major histocompatibility complex class I pp65₄₉₅_-₅₀₃ multimers, as well as CD28 and CD45 memory markers, were used to detect immune reconstitution in blood specimens from HCT recipients enrolled in the Phase Ib clinical trial. Specimens from the 10 (out of 18) vaccinated patients who had adequate (≥.2%) multimer binding to allow for memory analysis showed highly differentiated TEM and TEMRA phenotypes for pp65_495-503-specific CD8 T cells during the first 100days post-transplantation. In particular, by day 70, during the period of highest risk for CMV reactivation, combined TEM and TEMRA phenotypes constituted a median of 90% of pp65_495-503-specific CD8 T cells in these vaccinated patients. CMV viremia was not detectable in the patients who received CMVPepVax, although their pp65_495-503-specific CD8 T cell profiles were strikingly similar to those observed in viremic patients who did not receive the vaccine. Collectively, our findings indicate that in the absence of clinically relevant viremia, CMVPepVax reconstituted significant levels of differentiated pp65_495-503-specific CD8 TEMs early post-HCT. Our data indicate that the rapid reconstitution of CMV-specific T cells with marked levels of effector phenotypes may have been key to the favorable outcomes of the CMVPepVax clinical trial.

2016-02-01·The Lancet Haematology1区 · 医学

Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial

1区 · 医学

Article

作者: Farol, Len ; Snyder, David S ; Drake, Jennifer ; Cai, Ji-Lian ; Forman, Stephen J ; La Rosa, Corinna ; Diamond, Don J ; Zhou, Qiao ; Aldoss, Ibrahim ; Lampa, Melanie G ; Slape, Cynthia ; Salhotra, Amandeep ; Nakamura, Ryotaro ; Longmate, Jeffrey ; Zaia, John A ; O'Donnell, Margaret ; Miller, Jeffrey S

BACKGROUNDPatients seropositive for cytomegalovirus (CMV) and undergoing allogeneic haemopoietic stem-cell transplantation (HCT) are at risk for CMV reactivation. Stimulating viral immunity by vaccination might achieve CMV viraemia control without the need for antiviral agents. CMVPepVax is a chimeric peptide composed of a cytotoxic CD8 T-cell epitope from CMV pp65 and a tetanus T-helper epitope. It is formulated with the adjuvant PF03512676, a Toll-like receptor 9 agonist, which augments cellular immunity. We aimed to assess safety, immunogenicity, and possible clinical benefit of the CMVPepVax vaccine in patients undergoing HCT.METHODSWe did a randomised, open-label, phase 1b trial at one transplant centre in the USA. Eligible patients were CMV-seropositive, positive for HLA-A*0201, aged 18-75 years, and undergoing HCT from a matched-related or matched-unrelated donor. Patients were reassessed for eligibility on day 28 after HCT. We randomly allocated patients to either the CMVPepVax vaccine or observation, in blocks stratified by CMV donor serostatus. CMVPepVax was administered subcutaneously on days 28 and 56. The primary outcome was safety, which consisted of secondary graft failure, grade III-IV acute GVHD, non-relapse mortality by day 100, serious adverse events related to the vaccine (judged by the data and safety monitoring committee [DSMC]) grade 3-4 adverse events related to the vaccine (judged by the DSMC) within 2 weeks of vaccination, and development of double-strand (ds) DNA autoantibodies. Statistical analyses included all randomised patients and were done per-protocol. This study is registered with ClinicalTrials.gov, number NCT01588015. This trial is closed to accrual and the final analysis is presented in this report.FINDINGSBetween Oct 31, 2012, and Nov 5, 2014, 36 eligible patients were allocated to either CMVPepVax (n=18) or observation (n=18), with no adverse effect on HCT (no secondary graft failures in either group) or cases of acute GVHD (seven patients assigned vaccine and six under observation had acute GVHD of grade 2 or less), and no unexpected adverse events. Compared with observation, better relapse-free survival was recorded in patients allocated the vaccine (seven vs one; hazard ratio [HR] 0·12, 95% CI 0·01-0·94; p=0·015). No patients had non-relapse mortality by day 100. One serious adverse event (grade 1 fever) was attributed to CMVPepVax but resolved within 48 h. Four patients assigned the vaccine had a serious adverse event, which was unrelated to the vaccine (grade 3 thrombocytopenia, grade 3 device-related infection, grade 2 nausea, and grade 1 fever), compared with nine patients under observation (grade 4 maculopapular rash, grade 3 nausea, grade 3 infection, grade 3 thrombotic thrombocytopenic purpurea, grade 2 nausea, grade 2 generalised muscle weakness, grade 2 infection, grade 1 fever, and grade 1 fatigue; p=0·16). 54 grade 3-4 adverse events were reported in patients assigned the vaccine compared with 91 in patients who were under observation (p=0·2). No patients had grade III-IV acute GVHD or developed dsDNA autoantibodies.INTERPRETATIONThe results show safety and immunogenicity of the CMVPepVax vaccine. The prospect of substantial clinical benefits warrant testing in a phase 2 trial.FUNDINGNational Cancer Institute.

2004-05-01·Human Immunology4区 · 医学

Progress made towards the development of a CMV peptide vaccine

4区 · 医学

Review

作者: S.J Paston ; I.A Dodi ; J.A Madrigal

Cytomegalovirus disease still remains a major cause of morbidity and mortality in hematopoietic stem cell transplantation recipients. The cell-mediated immune response is essential in the maintenance of latency and the resolution of primary infections. The identification of immunodominant cytomegalovirus antigens has enabled researchers to determine the best candidate antigens to be included in a cytomegalovirus vaccine. Such a vaccine would have to stimulate both a cell-mediated and humoral immune response. Recent advances have enabled the rapid identification of minimal cytotoxic epitopes required to trigger such responses. Epitope mapping to date has mainly focused on the pp65 antigen but other antigens such as IE1 are starting to be mapped. A human leukocyte antigen allele hierarchy is starting to emerge that is dependent on the alleles present in an individual; this is relevant when considering what peptides should be included in a vaccine. This review looks at the current methods available for epitope mapping and the progress that has been made to date.

100 项与 Cytomegalovirus peptide vaccine(City of Hope National Medical Center) 相关的药物交易

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外链

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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
巨细胞病毒感染	临床3期	-	University of Minnesota	-
成人急性髓性白血病	临床2期	美国	City of Hope National Medical Center	2015-05-21
成人急性髓性白血病	临床2期	美国	National Cancer Institute	2015-05-21
加速期慢性骨髄性白血病	临床2期	美国	National Cancer Institute	2015-05-21
骨髓增生异常综合征	临床2期	美国	City of Hope National Medical Center	2015-05-21
骨髓增生异常综合征	临床2期	美国	National Cancer Institute	2015-05-21
骨髓纤维化	临床2期	美国	City of Hope National Medical Center	2015-05-21
骨髓纤维化	临床2期	美国	National Cancer Institute	2015-05-21
骨髓增生性疾病	临床2期	美国	National Cancer Institute	2015-05-21
骨髓增生性疾病	临床2期	美国	City of Hope National Medical Center	2015-05-21

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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


NCT02396134 (CTgov)	临床2期	霍奇金淋巴瘤 \| 慢性期慢性髓性白血病 \| 慢性淋巴细胞白血病 \| 成人急性髓性白血病 \| 巨细胞病毒感染 \| 骨髓增生性疾病 \| 成人急性淋巴细胞白血病 \| 加速期慢性骨髄性白血病 \| 多发性骨髓瘤 \| 骨髓纤维化 \| 非霍奇金淋巴瘤 \| 骨髓增生异常综合征 \| 淋巴母细胞淋巴瘤	61	Laboratory Biomarker Analysis+CMVpp65-A0201 peptide vaccine (Arm I (CMVpp65-A0201 Peptide Vaccine))	鹹構製構壓窪壓窪蓋鬱(網繭構獵獵餘顧築範蓋) = 鏇壓積選鑰鏇鹽齋餘網簾齋膚積蓋醖築鏇鏇夢 (糧憲糧夢簾構衊簾壓餘, 遞廠膚艱顧繭鬱夢構蓋 ~ 繭蓋淵窪醖鑰鏇觸艱選) 更多	-	2023-07-12
				Placebo (Arm II (Placebo))	鹹構製構壓窪壓窪蓋鬱(網繭構獵獵餘顧築範蓋) = 遞網襯鏇淵鹽廠範餘膚簾齋膚積蓋醖築鏇鏇夢 (糧憲糧夢簾構衊簾壓餘, 繭製壓襯願範鬱簾醖鏇 ~ 繭鏇鑰鑰範壓淵鬱鹹鹽) 更多
NCT02396134 (ASH 12021 \| ASH 22021) 人工标引	临床2期	巨细胞病毒感染	61	Cmvpepvax	範願鬱鏇獵簾選膚襯顧(餘鏇網襯廠醖鏇糧鏇築) = 繭膚獵夢選繭膚艱襯繭鹽構鬱鑰選顧遞壓構壓 (憲鏇壓憲鑰觸艱廠選憲 )	不佳	2021-11-05
				Placebo	範願鬱鏇獵簾選膚襯顧(餘鏇網襯廠醖鏇糧鏇築) = 壓淵窪構範膚艱鑰淵淵鹽構鬱鑰選顧遞壓構壓 (憲鏇壓憲鑰觸艱廠選憲 )
Tandem Meetings ASTCT and CIBMTR2019	N/A	造血干细胞移植	-	CMVPepVax	壓襯鑰網築簾膚積獵淵(糧獵鬱憲觸鬱憲網餘簾) = 顧築鑰鬱築獵窪鑰築鹽夢襯餘蓋製襯襯遞顧鹹 (鹹衊衊衊鏇襯簾鏇鬱膚 )	-	2019-03-01