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

Wake Forest University (WFU)

Status: Completed

Conditions: Oligodendroglioma; Glioma; Astrocytoma

Treatments: Biological: Tetanus Toxoid Vaccine; Biological: Hepatitis A Vaccine; Biological: Trivalent Influenza Vaccine; Other: Laboratory Biomarker Analysis

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT02747407

P30CA012197 (U.S. NIH Grant/Contract)

CCCWFU 01316 (Other Identifier)

IRB00037250

NCI-2016-00472 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 55 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

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

Trial design

55 participants in 2 patient groups

Basic Science Group II (vaccination at 9 months)

Description:

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.

Treatment:

Other: Laboratory Biomarker Analysis

Biological: Trivalent Influenza Vaccine

Biological: Hepatitis A Vaccine

Biological: Tetanus Toxoid Vaccine

Basic Science Groups I (vaccination pre-treatment)

Description:

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.

Treatment:

Other: Laboratory Biomarker Analysis

Biological: Trivalent Influenza Vaccine

Biological: Hepatitis A Vaccine

Biological: Tetanus Toxoid Vaccine