Booster Dose Trial

Safety and Efficacy of Booster Doses of COVID-19 Vaccine in Immunocompromised Patients With a Cancer Diagnosis

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.

Study Overview

• Status: Terminated
• Conditions: Cancer
• Intervention / Treatment: Biological: BNT162b2 vaccine

Detailed Description

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:

For patients who did not seroconvert after three doses or had low antibody response (<1000 AU/mL as determined by in-house Abbott assay), it was hypothesized that a 'mix and match' strategy with a 2nd booster dose ("4th dose") of COVID-19 vaccine would induce seroconversion and improve boosting of humoral antibody responses. To study this, a protocol was designed wherein patients who had received their 1st booster dose ("3rd dose") of mRNA vaccines and had undetectable anti-S antibody or had an anti-S antibody level of <1000 AU/mL measured at least 14 days after third dose would be randomized to an mRNA vs. adenoviral booster ("4th") vaccine dose. Responses would be then assessed at 4 weeks after the 2nd booster dose ("4th dose") through measurement of anti-S antibody results. Complete blood counts (CBC), quantitative immunoglobulin levels (IgG, IgA, and IgM), lymphocyte subsets, T-cell responses, and neutralization activity at baseline and 4 weeks will be assessed for each of these patients. Following the implementation of this protocol, the Centers for Disease Control (CDC) published a statement that advised that the mRNA vaccines should be preferentially administered over the adenoviral vaccines given concern over rare side effects such as thrombocytopenia and thrombosis syndrome. Given this advisory, the protocol was amended to allow recruitment in a cohort that would receive a fourth dose of the BNT162b2 vaccine to comply with CDC guidelines.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (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.

Exclusion Criteria (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Booster dose	Biological: BNT162b2 vaccine; Administer an additional dose of the BNT162b2 mRNA vaccine to patients with cancer who have a negative SARS-CoV-2 Spike IgG at least 14 days after 2 doses of the mRNA vaccines (BNT162b2/mRNA-1273) or 28 days after the adenoviral based Ad26CoV2.S vaccine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Were Seronegative After Primary Series of COVID-19 Vaccinations	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.	4 weeks after administration of 1st booster dose
Percentage of Patients Who Were 'Responders' After 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)	4 weeks after administration of 2nd booster dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Anti-Spike Antibody (IgG) Titer	The number of patients with evaluable T-cell immune responses who demonstrated positive anti-S antibody (IgG) titers against SARS-CoV-2 after 1st booster dose of vaccine.	4 weeks after administration of 1st booster dose
Spike Antibody Titer	The median SARS-CoV-2 spike antibody (IgG) titer among the entire cohort at 4 weeks after administration of the 1st booster dose of vaccine was determined.	4 weeks after administration of 1st booster dose
Change in Anti-Spike Antibody Titer for Patients With Hematologic Malignancies	The median change in anti-S antibody titer for patients with Hematologic malignancies was determined.	Baseline to 4 weeks after administration of 1st booster dose
Change in Anti-Spike Antibody Titer for Patients With Solid Tumor Malignancies	The median change in anti-S antibody titer for patients with Solid tumor malignancies was determined.	Baseline to 4 weeks after administration of 1st booster dose
Change in Anti-Spike Antibody Titer Among Patients With Hematologic Malignancy by Type	Median change in Anti-S antibody titers was determined in patients who presented with Hematologic (either Lymphoid or Myeloid) malignancies.	Baseline to 4 weeks after administration of 1st booster dose
Percentage of Patients Seropositive/Seronegative Following 1st Booster Dose	Percentage of Patients who were either seropositive or seronegative following administration of 1st booster dose as demonstrated by anti-S antibody testing.	4 weeks after administration of 1st booster dose
Neutralizing Antibodies Detected Among Seropositive Patients	The GenScript surrogate virus neutralization assay was used to analyze samples from seropositive patients to detect for the presence of neutralizing antibodies. The percentage of patients with neutralizing antibodies was determined.	4 weeks after administration of 1st booster dose
Positive T-cell Response Among Patients With a Negative Anti-S Antibody	Percentage of patients with a negative anti-S antibody following 1st booster dose who demonstrated a Positive T-cell response.	4 weeks after administration of 1st booster dose
Positive T-cell Response Among Patients With a Negative T-cell Response at Baseline	Percentage of patients who demonstrated a Positive T-cell response among those who demonstrated a negative T-cell response at baseline.	4 weeks after administration of 1st booster dose
Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy Within 6 Months of Treatment	In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed for patients on anti-CD20 antibody therapy within 6 months of administration of 1st booster dose.	Within 6 months prior to treatment to 4 weeks after administration of 1st booster dose
Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy	In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed for patients on anti-CD20 antibody therapy just prior to the study.	Baseline to 4 weeks after administration of 1st booster dose
Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy	In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed for patients not on anti-CD20 antibody therapy just prior to the study.	Baseline 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	In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed 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
Percentage of Patients Who Remained Seropositive Following 1st Booster Dose	Percentage of Patients who maintained a positive anti-S antibody (seropositive) following administration of 1st booster dose as demonstrated by anti-S antibody testing.	~4-6 months after administration of 1st booster dose
Percentage of Seronegative Patients Before 2nd Booster Dose	The percentage of patients determined to be seronegative 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
Percentage of Patients With Low (Anti-S Antibody) Serum Antibodies	The percentage of patients with low serum antibodies before administration of the 2nd booster dose was determined by assay. Patients with anti-S antibody titers of <1000 AU/mL were determined to have low 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	The percentage of patients who were classified as 'responders' after the 2nd Booster dose. A patient was classified as a responder if they: (1) had positive anti-S antibody at 4 weeks if seronegative after 1st booster dose or (2) if they achieved a titer of >1000 AU/mL at 4 weeks if they were sero-low after 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
Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Remained Seronegative Following 1st Booster Dose	Rate was determined as the percentage of patients demonstrating booster-induced seroconversion to positive anti-S antibody who had remained seronegative following administration of Primary Vaccination series and 1st Booster dose of BNT162b2, mRNA-1273, or AdCoV2.S COVID vaccine.	~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	The percentage of Patients with low anti-Spike antibody, determined to be IgG <1000 AU/mL by assay, who responded following administration of 2nd booster dose. Responses in this context were determined to be those patients with assay results of IgG > 1000 AU/mL.	~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	The median Anti-S antibody titer following administration of the primary vaccination series and 1st booster dose in Cohort B was determined.	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 Antibody Titer Following Administration of 2nd Booster Dose	The median Anti-S antibody titer following administration of the 2nd booster dose (Cohort B) was determined.	~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
Positive Anti-Spike Antibody (IgG) Titer Prior to 2nd Booster Dose	The number of Cohort B patients with evaluable T-cell immune responses who demonstrated positive anti-S antibody (IgG) titers against SARS-CoV-2 following 1st booster dose and prior to 2nd booster dose of vaccine.	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	The percentage of Cohort B patients who demonstrated positive anti-S antibody (IgG) titers against SARS-CoV-2 following administration of 2nd booster dose of vaccine.	~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	Neutralization activity against the WT variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported.	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 Wildtype (WT) SARS-CoV-2 Variant Following 2nd Booster Dose	Neutralization activity against the WT variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported.	~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 Omicron BA.1 SARS-CoV-2 Variant Prior to 2nd Booster Dose	Neutralization activity against the Omicron BA.1 variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported.	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	Neutralization activity against the Omicron BA.1 variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported.	~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

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Collaborators: National Cancer Institute (NCI); Albert Einstein College of Medicine; The Leukemia and Lymphoma Society
• Investigators: Principal Investigator: Balazs Halmos, MD, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2021
• Primary Completion (Actual): April 20, 2022
• Study Completion (Actual): May 21, 2023

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 16, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: July 5, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Booster; COVID-19
• Other Study ID Numbers: 2021-13204; 2UG1CA189859-06 (U.S. NIH Grant/Contract); IRV-BC0004-22 (Other Grant/Funding Number: Leukemia & Lymphoma Society); 3P30CA013330-49S3 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No