Safety and Efficacy of Booster Doses of COVID-19 Vaccine in Immunocompromised Patients With a Cancer Diagnosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 106
- 试验地点
- 2
- 主要终点
- Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Were Seronegative After Primary Series of COVID-19 Vaccinations
研究概览
简要总结
The goal of this study is to assess the safety and effectiveness of COVID vaccine booster doses in patients with cancer who have not developed an antibody after the U.S. Food and Drug Administration (FDA) Emergency Use Authorized COVID primary vaccination series.
详细描述
Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. Many healthcare regulatory agencies recommend administering 'booster' doses of COVID-19 vaccines beyond the standard two-dose series, for this group of patients. Therefore, studying the efficacy of these additional vaccine doses against SARS-CoV-2 and variants of concern is of utmost importance in this immunocompromised patient population.
The investigator team designed a prospective single arm clinical trial for consenting patients with cancer who had received two doses of mRNA, or one dose of AD26.CoV2.S vaccine, and were administered a third dose of mRNA vaccine. Patients who had no or low responses to three mRNA COVID vaccines were administered a fourth dose of mRNA vaccine. Efficacy was assessed by changes in anti-spike antibody, T-cell activity, and neutralization activity, at baseline and 4 weeks.
First Booster Dose ("3rd dose") study:
Following the informed consent process patients are enrolled into the study. After drawing baseline laboratory samples that include spike antibody, a sample for T-cell assay, and a biobank sample, patients will receive a third mRNA vaccine (initially BNT162b2 per protocol, later amended to allow for a third mRNA-1273 vaccine after the Food and Drug Administration [FDA] authorized 'booster' doses in the fall of 2021). Patients who had received Ad26.CoV2.S vaccine will receive a BNT162b2 booster vaccine. Follow-up visits are scheduled at ~4 weeks and 4-6 months following the booster dose and laboratory sample collections will be repeated.
Second Booster Dose ("4th dose") study:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(Cohort 1):
- •Above the age of 18
- •Meet one of the sub-criteria below:
- •Meet the CDC definition for immunocompromised status for cancer patients, i.e patients receiving active treatment for solid tumor or hematologic malignancy OR
- •Be a recipient of stem cell transplant or CAR-T cell therapy in the last 2 years OR
- •Have a negative SARS-CoV-2 spike IgG despite standard vaccination series, irrespective of active/inactive cancer status, on observation, or active therapy.
- •Underwent an in-person encounter at a study facility during the study period
- •Have received the second of the mRNA-based vaccines BNT162b2 and mRNA-1273 (Pfizer/BioNTech or Moderna, respectively) or one dose of the adenoviral Ad26CoV2.S (Johnson & Johnson) vaccine at least 28 days before the booster dose.
排除标准
- •(Cohort 1):
- •Patients who have had a serious adverse reaction to any prior COVID-19 vaccines resulting in emergency room visit or hospitalization, had events related to myocarditis, thrombosis and thrombocytopenia syndrome or anaphylaxis to any prior dose of the COVID-19 vaccines.
- •Patients who have had a documented COVID-19 infection in the 90 days prior to starting the study
- •Inclusion Criteria (Cohort 2):
- •Above the age of 18
- •Have a diagnosis of prior or active malignancy, either hematological or solid tumor
- •Have a negative or low-level SARS-CoV-2 spike IgG after 14 days of booster vaccination series irrespective of active/inactive cancer status, on observation, or active therapy.
- •Have received an FDA-authorized booster dose of mRNA (BNT162b2 and mRNA-1273) vaccine at least 28 days before study enrollment.
- •Exclusion Criteria (Cohort 2):
- •Patients who have had a serious adverse reaction to any prior COVID-19 vaccines resulting in emergency room visit or hospitalization, had events related to myocarditis, thrombosis and thrombocytopenia syndrome or anaphylaxis to any prior dose of the COVID-19 vaccines.
- •Patients who have had a documented COVID-19 infection in the 90 days prior to study enrollment
结局指标
主要结局
Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Were Seronegative After Primary Series of COVID-19 Vaccinations
时间窗: 4 weeks after administration of 1st booster dose
Rate will be determined as the percentage of patients demonstrating booster-induced seroconversion, as evidenced by anti-Spike antibody testing, who were seronegative after the primary series of FDA authorized COVID-19 vaccinations.
Percentage of Patients Who Were 'Responders' After 2nd Booster Dose
时间窗: 4 weeks after administration of 2nd booster dose
A patient was classified as a responder if they either (1) had positive anti-S antibody at 4 weeks if seronegative at baseline (following 1st booster dose) or (2) if they achieved a titer of \>1000 AU/mL at 4 weeks if they were sero-low at baseline (following 1st booster dose)
次要结局
- Change in Anti-Spike Antibody Titer Among Patients With Hematologic Malignancy by Type(Baseline to 4 weeks after administration of 1st booster dose)
- Positive T-cell Response Among Patients With a Negative T-cell Response at Baseline(4 weeks after administration of 1st booster dose)
- Neutralizing Antibodies Detected Among Seropositive Patients(4 weeks after administration of 1st booster dose)
- Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy Within 6 Months of Treatment(Within 6 months prior to treatment to 4 weeks after administration of 1st booster dose)
- Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy Within 6 Months of Treatment(Within 6 months prior to treatment to 4 weeks after administration of 1st booster dose)
- Positive Anti-Spike Antibody (IgG) Titer(4 weeks after administration of 1st booster dose)
- Spike Antibody Titer(4 weeks after administration of 1st booster dose)
- Positive T-cell Response Among Patients With a Negative Anti-S Antibody(4 weeks after administration of 1st booster dose)
- Percentage of Patients Who Remained Seropositive Following 1st Booster Dose(~4-6 months after administration of 1st booster dose)
- Percentage of Seronegative Patients Before 2nd Booster Dose(Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months)
- Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Remained Seronegative Following 1st Booster Dose(~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months)
- Change in Anti-Spike Antibody Titer for Patients With Hematologic Malignancies(Baseline to 4 weeks after administration of 1st booster dose)
- Change in Anti-Spike Antibody Titer for Patients With Solid Tumor Malignancies(Baseline to 4 weeks after administration of 1st booster dose)
- Percentage of Patients Seropositive/Seronegative Following 1st Booster Dose(4 weeks after administration of 1st booster dose)
- Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy(Baseline to 4 weeks after administration of 1st booster dose)
- Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy(Baseline to 4 weeks after administration of 1st booster dose)
- Percentage of Patients With Low (Anti-S Antibody) Serum Antibodies(Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months)
- Anti-spike IgG Responders After the 2nd Booster Dose(~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months)
- Anti-Spike Antibody Titer Following Administration of 2nd Booster Dose(~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months)
- Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Following 2nd Booster Dose(~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months)
- Percentage of Patients With Low Anti-Spike Antibody Who Responded Following 2nd Booster Dose(~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months)
- Anti-Spike Antibody Titer Following Administration of 1st Booster Dose(Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months)
- Positive Anti-Spike Antibody (IgG) Titer Prior to 2nd Booster Dose(Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months)
- Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Prior to 2nd Booster Dose(Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months)
- Positive Anti-Spike Antibody (IgG) Titer Following 2nd Booster Dose(~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months)
- Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Prior to 2nd Booster Dose(Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months)
- Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Following 2nd Booster Dose(~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months)