Evaluation of Human Immune Responses Vaccination in Patients With Lymphoma

Sponsor

Emory University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03501576

Collaborator

(none)

200

Enrollment

Locations

54.5

Anticipated Duration (Months)

100

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This clinical trial evaluates the influenza virus vaccination in evaluating human immune response in patients with lymphoma. Evaluating immune response may increase the understanding of how the immune system changes when patients receive treatment for lymphomas by looking at the antibody levels and the level of the different cells that make up the immune system over time compared to those without lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia Diffuse Large B-Cell Lymphoma Follicular Lymphoma Mantle Cell Lymphoma Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma	Biological: Inactivated Influenza Vaccine

Detailed Description

PRIMARY OBJECTIVE:

To determine the seroprotection and seroconversion rates after influenza or SARS-CoV2 vaccination in patients with lymphoma receiving active treatment or in follow up observation.

SECONDARY OBJECTIVES:

To characterize virus-specific plasmablasts and memory B cells after vaccination in patients with lymphoma receiving active treatment or in follow up observation.
To investigate the longevity of viral-specific humoral immunity to influenza virus in patients with lymphoma receiving active treatment or in follow up observation.
To assess the timing and strength of the peak immune response to vaccination.
To assess the effect of different lymphomas and treatment modalities in the immune response to vaccination.

OUTLINE:

Patients receive seasonal inactivated influenza vaccine intramuscularly (IM) at day 0.

After completion of study treatment, patients are followed up at days 7, 28, 90, 180, and 365.

Study Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Evaluation of Human Immune Responses Vaccination in Patients With Lymphoma

Actual Study Start Date :

Apr 6, 2018

Anticipated Primary Completion Date :

Oct 22, 2022

Anticipated Study Completion Date :

Oct 22, 2022

Arms and Interventions

Arm	Intervention/Treatment
Inactivated Influenza Vaccine Patients will be vaccinated with an FDA approved seasonal inactivated influenza vaccine	Biological: Inactivated Influenza Vaccine Given seasonal inactivated influenza vaccine IM Other Names: Fluzone Quadrivalent Fluzone Quadrivalent Influenza Vaccine Quadrivalent Influenza Vaccine Quadrivalent Inactivated Influenza Vaccine Flu Vaccine
Qualifying subjects to receive a SARS-CoV2 vaccine. Patients receive a SARS-CoV2 vaccine.
Clinical Group Receiving SARS-CoV2 Booster Vaccines Patients receive a SARS-CoV2 vaccine.

Arm

Intervention/Treatment

Inactivated Influenza Vaccine

Patients will be vaccinated with an FDA approved seasonal inactivated influenza vaccine

Biological: Inactivated Influenza Vaccine

Given seasonal inactivated influenza vaccine IM

Other Names:

Fluzone Quadrivalent

Fluzone Quadrivalent Influenza Vaccine

Quadrivalent Influenza Vaccine

Quadrivalent Inactivated Influenza Vaccine

Flu Vaccine

Qualifying subjects to receive a SARS-CoV2 vaccine.

Patients receive a SARS-CoV2 vaccine.

Clinical Group Receiving SARS-CoV2 Booster Vaccines

Patients receive a SARS-CoV2 vaccine.

Outcome Measures

Primary Outcome Measures

Cohort 1: Percentage of subjects achieving seroprotection, defined as the percentage of subjects with a post-vaccination HI titer > 1:40 [Up to 180 days after immunization]
Rates of seroprotection will be calculated for each patient group, and 95% exact binomial confidence intervals will be estimated using the Clopper-Pearson method.
Percentage of subjects achieving seroconversion [Up to 180 days after immunization]
Seroconversion is defined as the percentage of subjects with either a pre-vaccination HI titer < 1:10 and a post-vaccination HI titer > 1:40 or a pre-vaccination HI titer > 1:10 and a minimum four-fold rise in post-vaccination HI antibody titer (day 0, 28). Rates of seroconversion will be calculated for each patient group, and 95% exact binomial confidence intervals will be estimated using the Clopper-Pearson method.
Cohort 2: Efficacy (immune response of COVID vaccines at least 7 days after the second dose. [Up to 365 days after immunization]
Assessments will be performed at baseline (time of enrollment), day 7 after first dose of SARS-CoV2 vaccine, day of second dose of vaccine, day 8 after second dose of vaccine, and days 90, 180, and 365.
Cohort 3: Efficacy (immune response) of COVID vaccines at least 7 days after each booster vaccine dose. [From baseline up to 365 days]
Assessments will be performed after each dose of SARS-CoV2 booster vaccine.

Secondary Outcome Measures

Measurement of virus-specific serum antibody levels after vaccination [Up to 180 days after immunization]
For serum antibody responses directed against the vaccine epitopes, endpoint IgG titers after vaccination at each time point will be determined.
Measurement of virus-specific plasmablasts (PBs) after influenza vaccination [Up to 180 days after immunization]
PBs responses against influenza or SARS-CoV2 will be determined by direct ex vivo enzyme-linked immunospot (ELISPOT). Changes in the PB population will be measured to assess the timing and strength of the peak immune response to vaccination.
Measurement of virus-specific memory B-cells (MBCs) after vaccination [Up to 180 days after immunization]
The frequency of hemagglutinin (HA)-specific immunoglobulin G (IgG)-secreting MBCs per total IgG-secreting cells after vaccination will be determined. Changes in the MBC population will be measured to assess the timing and strength of the peak immune response to vaccination.
Maximum fold rise in antibody titer [Up to 180 days after immunization]
Hemagglutination inhibition assays will be used to assess the timing and strength of the peak immune response to vaccination.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects with a diagnosis of lymphoma falling into the following categories:
B-NHL who have received 1 cycle of chemotherapy
B-NHL in complete remission and within 12 months after completion of chemotherapy
Chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) receiving ibrutinib for at least 1 month
B-NHL in complete remission for over 12 months
Aggressive peripheral T-cell lymphoma (PTCL) who have received 1 cycle of chemotherapy
Subject capable of providing written or electronic informed consent prior to initiation of any study procedures; subjects able to understand and comply with planned study procedures and be available for all study visits.
Screening labs must be within the following ranges or considered to be not clinically significant by the investigator:

Hematology:

Hemoglobin: 7.0-16.1 gm/dL
Platelet count: 10-600/µL
Subjects who have not received the seasonal influenza vaccine in the current flu season and are not suspected to have had an influenza infection in the current flu season *- Platelet count: 10-600/uL
For cohort 1: Subjects who have not received the seasonal influenza vaccine in the current flu season and are not suspected to have had an influenza infection in the current flu season.
For cohort 3: Subjects must have previously received at least 1 dose of SARS-CoV2 vaccine. Patients who have not receive a prior SARS-CoV2 vaccine will be eligible to enroll in cohort.

Exclusion Criteria:

Known infection with human immunodeficiency virus (HIV). This information will be obtained verbally from the patient
Have any medical disease or condition that, in the opinion of the site principal investigator is a contraindication to study participation; this includes any chronic medical condition, defined as persisting 3 months (defined as 90 days) or longer, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject?s successful completion of this study
Have an acute illness, as determined by the site principal investigator within 72 hours prior to study vaccination; an acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol and was not due to an influenza infection
Subjects taking long-term systemic steroids defined as greater than 3 months in the past 12 months
Have known hypersensitivity or allergy to eggs, egg or chicken protein, or other components of the study vaccine
Have a history of Guillain-Barre syndrome (GBS)
Subjects who had or are suspected to have had an influenza infection in the current influenza season
Subjects who, at screening, have abnormal vital signs and/or physical exam, including a temperature ≥ 38.0 C, systolic blood pressure ≤ 90 or > 180 mmHg, pulse ≤ 60 or > 130 beats per minute, new rash, signs of infection
Subjects who have already received the seasonal influenza vaccine in the current influenza vaccination season
Subjects enrolled in hospice or whose life expectancy is less than 6 months