Booster Dose Trial

NCT ID: NCT05016622

Last Updated: 2024-07-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-10
• Study Completion Date: 2023-05-21

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.

Conditions

Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Booster dose

Group Type: EXPERIMENTAL

BNT162b2 vaccine

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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.

• 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Albert Einstein College of Medicine

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

The Leukemia and Lymphoma Society

OTHER

Sponsor Role: collaborator

Montefiore Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Balazs Halmos, MD

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center

Locations

Montefiore Medical Center

The Bronx, New York, United States

Countries

United States

References

Thakkar A, Pradhan K, Duva B, Carreno JM, Sahu S, Thiruthuvanathan V, Campbell S, Gallego S, Bhagat TD, Rivera J, Choudhary G, Olea R, Sabalza M, Shapiro LC, Lee M, Quinn R, Mantzaris I, Chu E, Will B, Pirofski LA, Krammer F, Verma A, Halmos B. Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trial. Elife. 2023 Mar 28;12:e83694. doi: 10.7554/eLife.83694.

Reference Type: DERIVED

PMID: 36975207 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2UG1CA189859-06

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRV-BC0004-22

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

3P30CA013330-49S3

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2021-13204

Identifier Type: -

Identifier Source: org_study_id