Booster Dose Trial

Phase 2

Terminated

Conditions: Cancer

Interventions: Biological: BNT162b2 vaccine

Registration Number: NCT05016622

Lead Sponsor: Montefiore Medical Center

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 106

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Booster dose	BNT162b2 vaccine	-

Primary Outcome Measures

Name	Time	Method
Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Were Seronegative After Primary Series of COVID-19 Vaccinations	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	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)

Secondary Outcome Measures

Name	Time	Method
Change in Anti-Spike Antibody Titer Among Patients With Hematologic Malignancy by Type	Baseline to 4 weeks after administration of 1st booster dose	Median change in Anti-S antibody titers was determined in patients who presented with Hematologic (either Lymphoid or Myeloid) malignancies.
Positive T-cell Response Among Patients With a Negative T-cell Response at Baseline	4 weeks after administration of 1st booster dose	Percentage of patients who demonstrated a Positive T-cell response among those who demonstrated a negative T-cell response at baseline.
Neutralizing Antibodies Detected Among Seropositive Patients	4 weeks after administration of 1st booster dose	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.
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	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.
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	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
Positive Anti-Spike Antibody (IgG) Titer	4 weeks after administration of 1st booster dose	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.
Spike Antibody Titer	4 weeks after administration of 1st booster dose	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.
Positive T-cell Response Among Patients With a Negative Anti-S Antibody	4 weeks after administration of 1st booster dose	Percentage of patients with a negative anti-S antibody following 1st booster dose who demonstrated a Positive T-cell response.
Percentage of Patients Who Remained Seropositive Following 1st Booster Dose	~4-6 months after administration of 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.
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	The percentage of patients determined to be seronegative before 2nd booster dose
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	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.
Change in Anti-Spike Antibody Titer for Patients With Hematologic Malignancies	Baseline to 4 weeks after administration of 1st booster dose	The median change in anti-S antibody titer for patients with Hematologic malignancies was determined.
Change in Anti-Spike Antibody Titer for Patients With Solid Tumor Malignancies	Baseline to 4 weeks after administration of 1st booster dose	The median change in anti-S antibody titer for patients with Solid tumor malignancies was determined.
Percentage of Patients Seropositive/Seronegative Following 1st Booster Dose	4 weeks after administration of 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.
Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy	Baseline to 4 weeks after administration of 1st booster dose	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.
Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy	Baseline to 4 weeks after administration of 1st booster dose	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.
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	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.
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	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.
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	The median Anti-S antibody titer following administration of the 2nd booster dose (Cohort B) was determined.
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	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.
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	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.
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	The median Anti-S antibody titer following administration of the primary vaccination series and 1st booster dose in Cohort B was determined.
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	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.
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	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.
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	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.
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 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.
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	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.