Qualitative, Qualitative, and Functional Studies Over the First Year in Measuring Immune System Response During the First Year of Therapy in Patients With Brain Tumors

Completed

• Conditions: Astrocytoma; Glioma; Oligodendroglioma
• Interventions: Biological: Hepatitis A Vaccine; Other: Laboratory Biomarker Analysis; Biological: Tetanus Toxoid Vaccine; Biological: Trivalent Influenza Vaccine

• Registration Number: NCT02747407
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

This research trial studies qualitative, qualitative, and functional studies over the first year in measuring immune system response in patients with brain tumors. Measuring the number of immune cells, whether these immune cells work correctly, and response to 2 vaccines at several times during the first year of treatment may help find out how active the immune system responds to fight infection and cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. To describe the quantity of immune cells underlying the antitumor immune response including dendritic cells, naive and activated T- and B-cells, regulatory T-cells, and natural killer cells.

II. To determine the proliferative ability of lymphocytes via T-cell activation.

SECONDARY OBJECTIVES:

I. To describe the immunologic response to the hepatitis A vaccine (or hepatitis B vaccine in those who are hepatitis A exposed) in comparison to expected/known normal responses either prior to (i.e. pre-treatment) or following chemoradiation (i.e. post-treatment).

II. To describe the immunologic response to tetanus toxoid vaccination compared to expected/known normal responses either prior to (i.e. pre-treatment) or following chemoradiation (i.e. post-treatment).

TERTIARY OBJECTIVES:

I. To describe the immunologic response to the yearly influenza vaccination over the course of the first year of therapy for glioma (timing of administration will be when clinically indicated over this year of therapy).

II. To describe the frequency of viral infection in glioma patients hospitalized during the respiratory viral season within year 1 of therapy.

III. To describe the overall survival of glioma patients enrolled in this study and describe the overall survival in these patients by changes in immunologic function.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive standard of care hepatitis A or B vaccine, tetanus toxoid vaccine, and trivalent influenza vaccine and then undergo standard of care treatment external beam radiation therapy and receive standard of care temozolomide. Patients also undergo collection of blood Samples monthly for the first 8 months and then bimonthly for up to 12 months for analysis via flow cytometry, carboxyfluorescein diacetate succinimidyl ester (CFSE) assay, live cell/dead cell distinction assay, and determination of naïve and memory immune response.

GROUP II: Patients undergo standard of care treatment and collection of blood samples as in Group I. Patients then receive hepatitis A and tetanus toxoid vaccinations at month 9.

Study Timeline

• Study First Submitted: 2016-04-19
• Study First Submitted QC: 2016-04-20
• Study First Posted: 2016-04-21
• Study Start: 2016-05
• Primary Completion: 2020-01
• Study Completion: 2021-09-09
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-28
• Last Update Posted: 2021-10-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

• Clinically or histologically diagnosed primary central nervous system astrocytoma or oligodendroglioma of World Health Organization grade II, III or IV
• Anticipated to undergo treatment with concurrent chemoradiation with conformal external beam radiotherapy in combination with low-dose temozolomide (75 mg/m^2) followed by adjuvant temozolomide (150-200 mg/m^2)
• Able to provide informed consent
• Karnofsky performance status >= 50%
• Willing and able to receive the tetanus toxoid and hepatitis vaccination (though prior vaccination with either vaccine is not a contraindication to eligibility)

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Exclusion Criteria

• Concurrent enrollment on an experimental study involving an agent whose primary mechanism of action is the immune system (i.e. immune checkpoint inhibition, oncologic vaccine, or other immune-directed therapies); Note: patients enrolled on an experimental study or receiving another concurrent treatment in addition to standard chemoradiation whose primary mechanism of action is NOT the immune system will be eligible for enrollment

• Patients unable to receive tetanus toxoid vaccination

  • Guillain-Barré syndrome =< 6 weeks after previous dose of a tetanus toxoid-containing vaccine; unstable neurologic condition (e.g., cerebrovascular events and acute encephalopathic conditions) which does not include the patient's primary brain tumor; history of an Arthus reaction following a previous dose of a tetanus toxoid-containing and/or diphtheria toxoid-containing vaccine

• Patients unable to receive hepatitis vaccination

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Basic Science Group II (vaccination at 9 months)	Hepatitis A Vaccine	Patients undergo standard of care treatment and collection of blood samples as in Group I. Patients then receive hepatitis A and tetanus toxoid vaccinations at month 9.
Basic Science Groups I (vaccination pre-treatment)	Tetanus Toxoid Vaccine	Patients receive standard of care hepatitis A or B vaccine, tetanus toxoid vaccine, and trivalent influenza vaccine and then undergo standard of care treatment external beam radiation therapy and receive standard of care temozolomide. Patients also undergo collection of blood Samples monthly for the first 8 months and then bimonthly for up to 12 months for analysis via flow cytometry, (CFSE) assay, live cell/dead cell distinction assay, and determination of naïve and memory immune response.
Basic Science Groups I (vaccination pre-treatment)	Hepatitis A Vaccine	Patients receive standard of care hepatitis A or B vaccine, tetanus toxoid vaccine, and trivalent influenza vaccine and then undergo standard of care treatment external beam radiation therapy and receive standard of care temozolomide. Patients also undergo collection of blood Samples monthly for the first 8 months and then bimonthly for up to 12 months for analysis via flow cytometry, (CFSE) assay, live cell/dead cell distinction assay, and determination of naïve and memory immune response.
Basic Science Group II (vaccination at 9 months)	Laboratory Biomarker Analysis	Patients undergo standard of care treatment and collection of blood samples as in Group I. Patients then receive hepatitis A and tetanus toxoid vaccinations at month 9.
Basic Science Group II (vaccination at 9 months)	Trivalent Influenza Vaccine	Patients undergo standard of care treatment and collection of blood samples as in Group I. Patients then receive hepatitis A and tetanus toxoid vaccinations at month 9.
Basic Science Groups I (vaccination pre-treatment)	Laboratory Biomarker Analysis	Patients receive standard of care hepatitis A or B vaccine, tetanus toxoid vaccine, and trivalent influenza vaccine and then undergo standard of care treatment external beam radiation therapy and receive standard of care temozolomide. Patients also undergo collection of blood Samples monthly for the first 8 months and then bimonthly for up to 12 months for analysis via flow cytometry, (CFSE) assay, live cell/dead cell distinction assay, and determination of naïve and memory immune response.
Basic Science Groups I (vaccination pre-treatment)	Trivalent Influenza Vaccine	Patients receive standard of care hepatitis A or B vaccine, tetanus toxoid vaccine, and trivalent influenza vaccine and then undergo standard of care treatment external beam radiation therapy and receive standard of care temozolomide. Patients also undergo collection of blood Samples monthly for the first 8 months and then bimonthly for up to 12 months for analysis via flow cytometry, (CFSE) assay, live cell/dead cell distinction assay, and determination of naïve and memory immune response.
Basic Science Group II (vaccination at 9 months)	Tetanus Toxoid Vaccine	Patients undergo standard of care treatment and collection of blood samples as in Group I. Patients then receive hepatitis A and tetanus toxoid vaccinations at month 9.

Primary Outcome Measures

Name	Time	Method
Proliferative ability of lymphocytes by carboxyfluorescein diacetate succinimidyl ester assay	Up to 1 year	Mean values of the quantitative measures and proliferative ability will be calculated for each four time points and compared to determine the trajectory over time as described. In addition, the repeated measures for quantitative measures will be displayed graphically with individual trajectories. The linear mixed model will be performed to identify predictors (e.g., sex) that are associated with the quantitative measures. Furthermore, the generalized estimating equations model with the logit link and binomial distribution will be used to identify predictors for qualitative measures (e.g., prol
The quantity of cells determined by flow cytometry	Up to 1 year	Mean values of the quantitative measures and proliferative ability will be calculated for each four time points and compared to determine the trajectory over time as described. In addition, the repeated measures for quantitative measures will be displayed graphically with individual trajectories. The linear mixed model will be performed to identify predictors (e.g., sex) that are associated with the quantitative measures. Furthermore, the generalized estimating equations model with the logit link and binomial distribution will be used to identify predictors for qualitative measures (e.g., prol

Secondary Outcome Measures

Name	Time	Method
Response of the tetanus toxoid vaccine-specific IgG antibody	At 28 days following tetanus toxoid vaccination	Baseline and day 28 geometric mean titers (GMTs) will be calculated for hepatitis A or B and tetanus. GMTs for patients undergoing vaccination pre- and post-treatment will be performed. The difference in 28 day GMT between pretreatment and posttreatment will be compared using the paired t test. Analysis of covariance will be used to identify predictors that are associated with the change of 28 day difference in GMT. Seroconversion or a 4-fold rise in GMT from baseline to day 28 will be determined for pre and post treatment patient cohorts. Seroconversion proportion will be compared against kno
Vaccine-specific total antibody response after hepatitis A vaccination. In hepatitis A exposed patients, hepatitis B will be used.	At 28 days post hepatitis A vaccination	Baseline and day 28 geometric mean titers (GMTs) will be calculated for each vaccine (i.e. hepatitis A or B and tetanus). GMTs for patients undergoing vaccination pre- and post-treatment will be performed. The difference in 28-day GMT between pre-treatment and post-treatment will be compared using the paired-t test. Analysis of covariance will be used to identify predictors that are associated with the change of 28-day difference in GMT. Seroconversion or a 4-fold rise in GMT from baseline to day-28 will be determined for pre- and post-treatment patient cohorts. Seroconversion proportion will

Trial Locations

Locations (1)

Comprehensive Cancer Center of Wake Forest University; 🇺🇸 Winston-Salem, North Carolina, United States