Phase 2 Defibrotide PPX in High Risk SCD Pts w/MAC&Haplo AlloSCT IND127812 9-3-15

具有 MAC 的高风险 SCD 患者中的第 2 期去纤维蛋白肽 PPX

基本信息

  • 批准号:
    9764133
  • 负责人:
  • 金额:
    $ 50万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-04-16 至 2021-08-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Sickle cell disease (SCD) is a rare orphan disease in the United States (US), affecting approximately 100,000 people in the US. SCD is characterized by severe vaso-occlusive disease, resulting in endothelial cell dysfunction, chronic organ damage, poor health-related quality of life (HRQL) and early mortality. The only known curative therapy for patients with high-risk SCD is allogeneic stem cell transplantation (AlloSCT) from an unaffected HLA-matched sibling donor (MSD). However, only 15% of high-risk patients with SCD have such donors. In the last grant cycle we successfully demonstrated the safety and feasibility of familial haploidentical (FHI) AlloSCT utilizing CD34 enrichment and CD3 (T cell) addback after myeloimmunoablative conditioning (MIAC) in children and adolescents (IND#14359) (5R01FD004090) (NCT61461837). During that grant cycle the CD34 enrichment methodology utilizing the CliniMACS® technology was approved by the FDA, in part due to the results of this investigation. Limitations of this approach include: 1) lack of safety data in young adults with high-risk SCD; 2) high risk of transplant-related mortality secondary to endothelial dysfunction and sinusoidal obstructive syndrome (SOS); and 3) potential for long-term toxicity, especially infertility. Defibrotide is a mixture of polydisperse oligonucleotides that targets small vessel endothelium with antithrombotic and fibrinolytic activity. Defibrotide is approved in Europe, but not the US, and has been demonstrated to reduce mortality significantly in patients who have develop severe SOS post-MIAC AlloSCT. Our FHI AlloSCT SCD consortium (www.sicklecelltransplantconsortium.org) has obtained a new IND (127812) to investigate the safety, feasibility and efficacy of defibrotide prophylaxis prior to and during MIAC and FHI AlloSCT utilizing CD34 enrichment and T cell addback in children, adolescents and young adults with high-risk SCD. The specific aims include (brief): 1) assess safety, toxicity and efficacy of defibrotide prophylaxis to prevent severe SOS; 2) investigate safety and efficacy of decreasing the dose of cyclophosphamide in the MIAC by 50%; 3) identify new endothelial biomarkers and methods of non-invasive hepatic imaging associated with SOS; 4) determine the incidence of late effects in the current and two new cohorts, with a focus on fertility preservation; 5) determine the probability of acute and chronic GVHD, and levels of whole blood and RBC-enriched donor chimerism, and cellular immune reconstitution; 6) estimate changes in pulmonary, cardiovascular and pulmonary vascular function; and 7) characterize changes in neuroimaging, neurocognitive function and HRQL. The long-term objectives are to obtain sufficient data to contribute to FDA approval of defibrotide prophylaxis to prevent severe SOS in high-risk patients with SCD, facilitate this successful therapeutic approach to at-risk young adults with SCD, reduce the dose of cyclophosphamide by 50% in the MIAC regimen and maintain robust hematopoietic and cellular immune reconstitution, donor chimerism, low risk of acute and chronic GVHD and a robust EFS/OS in patients with high-risk SCD without an HLA MSD.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Mitchell S. Cairo其他文献

Race/ethnicity, gender, socioeconomic status-research exploring their effects on child health: a subject review.
种族/民族、性别、社会经济地位——探讨其对儿童健康影响的研究:主题回顾。
  • DOI:
  • 发表时间:
    2000
  • 期刊:
  • 影响因子:
    8
  • 作者:
    P. Mccarthy;K. Christoffel;C. Dungy;M. Gillman;F. Rivara;J. Takayama;D. Alexander;J. Almquist;Mitchell S. Cairo;R. Chesney;C. Irwin;L. Margolis;E. Mcanarney;B. Dreyer;P. C. Dyck;E. Rothstein;D. Schonfeld;L. Simpson;R. C. Tsang;B. Yudowsky
  • 通讯作者:
    B. Yudowsky
Hematopoietic growth factors: a new frontier in immunotherapy.
造血生长因子:免疫治疗的新领域。
  • DOI:
    10.1016/s0022-3476(05)82181-x
  • 发表时间:
    1991
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Mitchell S. Cairo
  • 通讯作者:
    Mitchell S. Cairo
IGF1R- and ROR1-Specific Chimeric Antigen Receptor (CAR) T Cell Immunotherapy for Poor Risk Sarcomas
  • DOI:
    10.1016/j.bbmt.2014.11.686
  • 发表时间:
    2015-02-01
  • 期刊:
  • 影响因子:
  • 作者:
    Haein Park;Xin Huang;Joseph Greene;James Pao;Erin Mulvey;Sophia X. Zhou;Deepali Sachdev;Douglas Yee;Christoph Rader;Catherine M. Albert;Carl Hamby;David Loeb;Mitchell S. Cairo;Xianzheng Zhou
  • 通讯作者:
    Xianzheng Zhou
Decreased Stimulated GM-CSF Production and GM-CSF Gene Expression but Normal Numbers of GM-CSF Receptors in Human Term Newborns Compared with Adults
与成人相比,人类足月新生儿中受刺激的 GM-CSF 产生和 GM-CSF 基因表达减少,但 GM-CSF 受体数量正常
  • DOI:
  • 发表时间:
    1991
  • 期刊:
  • 影响因子:
    3.6
  • 作者:
    Mitchell S. Cairo;Mitchell S. Cairo;Y. Suen;Y. Suen;E. Knoppel;E. Knoppel;C. Ven;C. Ven;Anna Nguyen;Anna Nguyen;Leonard S. Sender;Leonard S. Sender
  • 通讯作者:
    Leonard S. Sender
The Use of Granulocyte Transfusions in Neonatal Sepsis
粒细胞输注在新生儿败血症中的应用
  • DOI:
  • 发表时间:
    1990
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Mitchell S. Cairo
  • 通讯作者:
    Mitchell S. Cairo

Mitchell S. Cairo的其他文献

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{{ truncateString('Mitchell S. Cairo', 18)}}的其他基金

A Randomized Study of Maternal Donor Derived CMV Cytotoxic T-Lymphocytes (CTLs) and Valganciclovir vs Valganciclovir in Neonates With Moderate/Severe Maternal Acquired CMV Infection
母体供体来源的 CMV 细胞毒性 T 淋巴细胞 (CTL) 和缬更昔洛韦与缬更昔洛韦在中度/重度母体获得性 CMV 感染新生儿中的随机研究
  • 批准号:
    10730709
  • 财政年份:
    2023
  • 资助金额:
    $ 50万
  • 项目类别:
Seventh International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma
第七届儿童、青少年和青年非霍奇金淋巴瘤国际研讨会
  • 批准号:
    10539036
  • 财政年份:
    2022
  • 资助金额:
    $ 50万
  • 项目类别:
CMV, ADV and EBV Viral Cytotoxic T-Lymphocytes Generated by a Novel Cytokine Capture System in Children, Adolescents and Young Adults with Refractory Viral Infection and T-Cell Immunodeficiency
新型细胞因子捕获系统在患有难治性病毒感染和 T 细胞免疫缺陷的儿童、青少年和年轻人中产生 CMV、ADV 和 EBV 病毒细胞毒性 T 淋巴细胞
  • 批准号:
    9807591
  • 财政年份:
    2019
  • 资助金额:
    $ 50万
  • 项目类别:
CMV, ADV and EBV Viral Cytotoxic T-Lymphocytes Generated by a Novel Cytokine Capture System in Children,Adolescents and Young Adults with Refractory Viral Infection and T-Cell Immunodeficiency
新型细胞因子捕获系统在患有难治性病毒感染和 T 细胞免疫缺陷的儿童、青少年和年轻人中产生 CMV、ADV 和 EBV 病毒细胞毒性 T 淋巴细胞
  • 批准号:
    10244910
  • 财政年份:
    2019
  • 资助金额:
    $ 50万
  • 项目类别:
CMV, ADV and EBV Viral Cytotoxic T-Lymphocytes Generated by a Novel Cytokine Capture System in Children,Adolescents and Young Adults with Refractory Viral Infection and T-Cell Immunodeficiency
新型细胞因子捕获系统在患有难治性病毒感染和 T 细胞免疫缺陷的儿童、青少年和年轻人中产生 CMV、ADV 和 EBV 病毒细胞毒性 T 淋巴细胞
  • 批准号:
    10466832
  • 财政年份:
    2019
  • 资助金额:
    $ 50万
  • 项目类别:
CMV, ADV and EBV Viral Cytotoxic T-Lymphocytes Generated by a Novel Cytokine Capture System in Children, Adolescents and Young Adults with Refractory Viral Infection and T-Cell Immunodeficiency
新型细胞因子捕获系统在患有难治性病毒感染和 T 细胞免疫缺陷的儿童、青少年和年轻人中产生 CMV、ADV 和 EBV 病毒细胞毒性 T 淋巴细胞
  • 批准号:
    10013179
  • 财政年份:
    2019
  • 资助金额:
    $ 50万
  • 项目类别:
Sixth International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma
第六届儿童、青少年和青年非霍奇金淋巴瘤国际研讨会
  • 批准号:
    9611656
  • 财政年份:
    2018
  • 资助金额:
    $ 50万
  • 项目类别:
1st Annual Tandem ASPHO/PBMTC Educational Mtg: New Frontiers in Pediatric AlloSCT
第一届年度串联 ASPHO/PMTC 教育 Mtg:儿科 AlloSCT 的新领域
  • 批准号:
    8529749
  • 财政年份:
    2013
  • 资助金额:
    $ 50万
  • 项目类别:
Ph2 of T-Cell Depl Familial Haploidentical SCT for tx Hi-Risk Sickle Cell Anemia
T 细胞 Depl 家族单倍相合 SCT 治疗 tx 高危镰状细胞性贫血的第二阶段
  • 批准号:
    8354332
  • 财政年份:
    2012
  • 资助金额:
    $ 50万
  • 项目类别:
Ph2 of T-Cell Depl Familial Haploidentical SCT for tx Hi-Risk Sickle Cell Anemia
T 细胞 Depl 家族单倍相合 SCT 治疗 tx 高危镰状细胞性贫血的第二阶段
  • 批准号:
    8459322
  • 财政年份:
    2012
  • 资助金额:
    $ 50万
  • 项目类别:

相似海外基金

Defibrotide for the treatment of severe hepatic veno-cc*
去纤苷用于治疗严重肝小静脉CC*
  • 批准号:
    7129042
  • 财政年份:
    2005
  • 资助金额:
    $ 50万
  • 项目类别:
defibrotide for the treatment of severe hepatic veno-cc*
去纤苷用于治疗严重肝小静脉CC*
  • 批准号:
    7129051
  • 财政年份:
    2004
  • 资助金额:
    $ 50万
  • 项目类别:
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