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

摘要 现在已经确定，癌症患者的COVID-19具有较高的发病率和死亡率， 特别是在血液恶性肿瘤患者中1，2。有效的疫苗已经开发出来， 由FDA授权对抗这种流行病3 - 5。然而，新出现的数据表明，尽管这些 疫苗在一般人群中诱导高水平的免疫力，血液恶性肿瘤患者 SARS-CoV-2刺突抗体的血清转化率较低6 - 9。事实上，我们之前的数据表明 目前FDA批准的Covid-19疫苗对大多数恶性肿瘤患者具有良好的免疫原性， 诊断，独特队列除外-血液恶性肿瘤患者和以下高度 免疫抑制疗法（SCT、CAR-T、抗CD20）。我们目前的研究计划解决的有效性， 在诊断为癌症的患者中接种Covid-19加强疫苗，特别关注以下患者 不可检测或低抗刺突IgG抗体水平。250名不同种族的患者，癌症 诊断和既往癌症治疗将入组本研究，对加强疫苗接种的反应将 使用标准抗刺突IgG以及试验性T细胞和病毒中和试验进行评估。在 此外，在第二个队列中，我们将确定"混合搭配"的疫苗接种策略是否可能在以下方面更成功： 在尽管加强免疫但抗体水平持续阴性/低的患者中实现可检测的免疫力 接种疫苗在该队列中，将招募100例通过抗加标IgG检测未出现 可检测到或具有低水平的体液免疫。这些患者将随机接受额外的 剂量的基于mRNA的疫苗（BNT162b2）与腺病毒疫苗（AdCov2.S）。 这些疫苗接种计划的安全性和有效性，并将提供24个月随访的长期数据 计划好了这些研究应提供关键信息，以最好地解决适当的保护策略， 被诊断为癌症的特殊弱势患者群体。

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.