Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

对现有 NIH 拨款和合作协议的行政补充（家长管理补充临床试验可选）

• 批准号: 10494563
• 负责人: EDWARD CHU
• 金额: $ 43.11万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-11-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10494563
• 关键词: 2019-nCoV; Address; Administrative Supplement; Antibodies; Antibody titer measurement; Biological Assay; CAR T cell therapy; COVID-19; COVID-19 booster; COVID-19 vaccination; COVID-19 vaccine; Cancer Patient; Case Study; Cellular Assay; Centers for Disease Control and Prevention (U.S.); Clinical Trials; Cohort Studies; Data; Diagnosis; Dose; Enrollment; Ethnic Origin; General Population; Grant; Hematologic Neoplasms; Hematology; Humoral Immunities; Immune; Immune response; Immunity; Immunocompromised Host; Immunoglobulin G; Immunologic Memory; Investigation; Laboratories; Malignant - descriptor; Malignant Neoplasms; Medical center; Moderna COVID-19 vaccine; Morbidity - disease rate; Organ Transplantation; Paper; Parents; Patients; Pfizer-BioNTech COVID-19 vaccine; RNA vaccination; RNA vaccine; Randomized; Recommendation; Research Design; SARS-CoV-2 negative; SARS-CoV-2 positive; Safety; Scheme; Secondary Immunization; Series; Solid; Solid Neoplasm; Stem cell transplant; T-Cell Activation; T-Lymphocyte; Testing; U-Series Cooperative Agreements; United States National Institutes of Health; Update; Vaccination; Vaccines; Viral; Virus; anti-CD20; antibody test; arm; base; booster vaccine; cancer diagnosis; cancer therapy; cohort; combat; coronavirus disease; follow-up; high risk; immunogenicity; inhibitor; mortality; neutralizing antibody; novel; patient population; primary endpoint; prospective; response; safety study; secondary endpoint; seroconversion; side effect; tositumomab; vaccination strategy

Abstract It is now well-established that COVID-19 in patients with cancer carries a higher morbidity and mortality, especially in amongst patients with hematologic malignancies1, 2. Effective vaccines have been developed and authorized by the FDA to combat this pandemic3-5. However, emerging data suggests that despite these vaccines inducing high levels of immunity in the general population, patients with hematologic malignancies have lower rates of seroconversion for the SARS-CoV-2 Spike antibody6-9. Indeed, our prior data had suggested excellent immunogenicity of the currently FDA authorized Covid-19 vaccines for most patients with a malignant diagnosis with exception of unique cohorts- patients with hematological malignancies and following highly immune suppressive therapies (SCT, CAR-T, anti-CD20). Our current study plans to address the efficacy of Covid-19 booster vaccinations amongst patients with a cancer diagnosis with a special focus on patients with undetectable or low anti-Spike IgG antibody levels. 250 patients with a diverse range of ethnicities, cancer diagnosis and prior cancer therapies will be enrolled in this study and the response to booster vaccinations will be assessed using standard anti-Spike IgG as well as investigational T cell and Virus Neutralization assays. In addition, in a second cohort we will define if a “mix and match” vaccination strategy might be more successful at achieving detectable immunity in patients with persistently negative/low antibody levels despite booster vaccinations. In this cohort, 100 patients will be accrued who by anti-spike IgG assays have not developed detectable or have low levels of humoral immunity. These patients will be randomized to receive an additional dose of an mRNA based vaccine (BNT162b2) versus an adenoviral vaccine (AdCov2.S).Both studies will assess safety and efficacy of these vaccination schemes and will provide long-term data with 24 months of follow up planned. These studies should provide critical information to best address proper protective strategies for uniquely vulnerable patient populations with a cancer diagnosis.

抽象的 现在，良好的癌症患者的Covid-19具有更高的发病率和死亡率， 尤其是在血液学恶性肿瘤患者中1，2。有效的疫苗已经开发出来，并且 由FDA授权与此大流行3-5作战。但是，新兴的数据表明希望这些 疫苗诱导普通人群中高水平的免疫力，血液学恶性肿瘤患者患有 SARS-COV-2 SPIKE抗体6-9的血清转化速率较低。确实，我们先前的数据建议 对于大多数恶性患者，目前FDA授权的Covid-19疫苗的出色免疫原性 除独特的队列 - 血液学恶性肿瘤患者外，诊断和高度关注 免疫抑制疗法（SCT，CAR-T，抗CD20）。我们目前的研究计划解决 癌症诊断患者的COVID-19助推器疫苗接种，特别关注患者 无法检测到的或低抗尖峰IgG抗体水平。 250名潜水员种族范围的患者，癌症 诊断和先前的癌症疗法将参加这项研究，对增强疫苗的反应将 使用标准抗尖峰IgG以及投资T细胞和病毒中和测定法进行评估。在 此外，在第二个队列中，我们将定义“混合和匹配”疫苗接种策略是否可能更成功 在持续阴性/低抗体水平助推器的患者中可检测到的免疫力 疫苗接种。在此队列中，将有100名因抗尖峰IgG测定的患者而造成的。 可检测或具有较低水平的体液免疫力。这些患者将被随机接收额外 基于mRNA的疫苗（BNT162B2）与腺病毒疫苗（ADCOV2.S）的剂量。 这些疫苗方案的安全性和易于性，并将提供长期数据，并随访24个月 计划。这些研究应提供关键信息，以最佳解决适当的保护策略 具有癌症诊断的独特脆弱患者人群。