Clinical trial NCT05016622: Booster Dose Trial
Official title: Safety and Efficacy of Booster Doses of COVID-19 Vaccine in Immunocompromised Patients With a Cancer Diagnosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cancer
Keywords: COVID-19
Booster
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
Collaborators: name: Albert Einstein College of Medicine
name: National Cancer Institute (NCI)
name: The Leukemia and Lymphoma Society
First posted: 2021-08-23
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Were Seronegative After Primary Series of COVID-19 Vaccinations
timeFrame: 4 weeks after administration of 1st booster dose
measure: Percentage of Patients Who Were 'Responders' After 2nd Booster Dose
timeFrame: 4 weeks after administration of 2nd booster dose
Secondary outcomes:
measure: Positive Anti-Spike Antibody (IgG) Titer
timeFrame: 4 weeks after administration of 1st booster dose
measure: Spike Antibody Titer
timeFrame: 4 weeks after administration of 1st booster dose
measure: Change in Anti-Spike Antibody Titer for Patients With Hematologic Malignancies
timeFrame: Baseline to 4 weeks after administration of 1st booster dose
measure: Change in Anti-Spike Antibody Titer for Patients With Solid Tumor Malignancies
timeFrame: Baseline to 4 weeks after administration of 1st booster dose
measure: Change in Anti-Spike Antibody Titer Among Patients With Hematologic Malignancy by Type
timeFrame: Baseline to 4 weeks after administration of 1st booster dose
measure: Percentage of Patients Seropositive/Seronegative Following 1st Booster Dose
timeFrame: 4 weeks after administration of 1st booster dose
measure: Neutralizing Antibodies Detected Among Seropositive Patients
timeFrame: 4 weeks after administration of 1st booster dose
measure: Positive T-cell Response Among Patients With a Negative Anti-S Antibody
timeFrame: 4 weeks after administration of 1st booster dose
measure: Positive T-cell Response Among Patients With a Negative T-cell Response at Baseline
timeFrame: 4 weeks after administration of 1st booster dose
measure: Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy Within 6 Months of Treatment
timeFrame: Within 6 months prior to treatment to 4 weeks after administration of 1st booster dose
measure: Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy
timeFrame: Baseline to 4 weeks after administration of 1st booster dose
measure: Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy
timeFrame: Baseline to 4 weeks after administration of 1st booster dose
measure: Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy Within 6 Months of Treatment
timeFrame: Within 6 months prior to treatment to 4 weeks after administration of 1st booster dose
measure: Percentage of Patients Who Remained Seropositive Following 1st Booster Dose
timeFrame: ~4-6 months after administration of 1st booster dose
measure: Percentage of Seronegative Patients Before 2nd Booster Dose
timeFrame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
measure: Percentage of Patients With Low (Anti-S Antibody) Serum Antibodies
timeFrame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
measure: Anti-spike IgG Responders After the 2nd Booster Dose
timeFrame: ~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
measure: Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Remained Seronegative Following 1st Booster Dose
timeFrame: ~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
measure: Percentage of Patients With Low Anti-Spike Antibody Who Responded Following 2nd Booster Dose
timeFrame: ~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
measure: Anti-Spike Antibody Titer Following Administration of 1st Booster Dose
timeFrame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
measure: Anti-Spike Antibody Titer Following Administration of 2nd Booster Dose
timeFrame: ~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
measure: Positive Anti-Spike Antibody (IgG) Titer Prior to 2nd Booster Dose
timeFrame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
measure: Positive Anti-Spike Antibody (IgG) Titer Following 2nd Booster Dose
timeFrame: ~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
measure: Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Prior to 2nd Booster Dose
timeFrame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
measure: Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Following 2nd Booster Dose
timeFrame: ~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
measure: Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Prior to 2nd Booster Dose
timeFrame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
measure: Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Following 2nd Booster Dose
timeFrame: ~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
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Balazs Halmos, MD
role: PRINCIPAL_INVESTIGATOR
References: