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

摘要 现在众所周知，新冠肺炎在癌症患者中具有更高的发病率和死亡率， 特别是在血液病患者中1，2。已经开发出有效的疫苗，并 由FDA授权抗击这场混乱3-5。然而，新出现的数据表明，尽管有这些 在普通人群中诱导高水平免疫的疫苗，恶性血液病患者 SARS-CoV-2刺突抗体的血清转换率较低6-9。事实上，我们之前的数据表明 美国食品和药物管理局目前批准的新冠肺炎疫苗对大多数恶性肿瘤患者具有良好的免疫原性 诊断除特殊队列外--血液系统恶性肿瘤患者和高度关注患者 免疫抑制治疗(SCT、CAR-T、抗CD20)。我们目前的研究计划解决以下问题： 新冠肺炎在确诊为癌症的患者中加强疫苗接种，特别关注患有 检测不到或低水平的抗斯派克抗体。250名不同种族的患者，癌症 诊断和以前的癌症治疗将被纳入这项研究，对加强疫苗接种的反应将 使用标准的抗Spike免疫球蛋白以及调查性T细胞和病毒中和试验进行评估。在……里面 此外，在第二个队列中，我们将定义“混合匹配”疫苗接种策略是否在 在抗体水平持续为阴性/低水平的患者中实现可检测的免疫 接种疫苗。在这个队列中，将有100名患者通过抗尖峰免疫球蛋白检测没有出现。 可检测到的或体液免疫水平较低的。这些患者将随机接受额外的 基于mRNA的疫苗(BNT162b2)与腺病毒疫苗(AdCov2.S)的剂量。这两项研究都将评估 这些疫苗接种计划的安全性和有效性，并将提供24个月的随访的长期数据 有计划的。这些研究应提供关键信息，以最好地处理适当的保护战略 被诊断为癌症的独一无二的脆弱患者群体。

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.