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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

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ClinicalTrials.gov Identifier: NCT02747407
Recruitment Status : Active, not recruiting
First Posted : April 21, 2016
Last Update Posted : April 22, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment
Astrocytoma Glioma Oligodendroglioma Biological: Hepatitis A Vaccine Other: Laboratory Biomarker Analysis Biological: Tetanus Toxoid Vaccine Biological: Trivalent Influenza Vaccine

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.

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Study Type : Observational
Actual Enrollment : 55 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Determining the Competence of the Immune System Over the First Year of Therapy in Patients With Glioma: A Battery of Quantitative, Qualitative and Functional Measures of Immune Readiness
Actual Study Start Date : May 2016
Actual Primary Completion Date : April 17, 2019
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Basic Science Group II (vaccination at 9 months)
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.
Biological: Hepatitis A Vaccine
Other Names:
  • Havrix
  • Hepatitis A Vaccine, Inactivated
  • Vaqta

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Tetanus Toxoid Vaccine
Other Names:
  • Tetanus Toxoid
  • TT

Biological: Trivalent Influenza Vaccine
Other Names:
  • Agriflu
  • Flu prevention
  • Flu prophylaxis
  • Flu shot
  • Flu vaccination
  • Fluarix
  • Flublok
  • FluLaval
  • Flushield
  • Fluvirin
  • Fluzone
  • Influenza Vaccine
  • Influenza Virus Vaccine, Trivalent, Types A and B
  • TIV

Basic Science Groups I (vaccination pre-treatment)
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.
Biological: Hepatitis A Vaccine
Other Names:
  • Havrix
  • Hepatitis A Vaccine, Inactivated
  • Vaqta

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Tetanus Toxoid Vaccine
Other Names:
  • Tetanus Toxoid
  • TT

Biological: Trivalent Influenza Vaccine
Other Names:
  • Agriflu
  • Flu prevention
  • Flu prophylaxis
  • Flu shot
  • Flu vaccination
  • Fluarix
  • Flublok
  • FluLaval
  • Flushield
  • Fluvirin
  • Fluzone
  • Influenza Vaccine
  • Influenza Virus Vaccine, Trivalent, Types A and B
  • TIV




Primary Outcome Measures :
  1. Proliferative ability of lymphocytes by carboxyfluorescein diacetate succinimidyl ester assay [ Time Frame: 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

  2. The quantity of cells determined by flow cytometry [ Time Frame: 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 :
  1. Response of the tetanus toxoid vaccine-specific IgG antibody [ Time Frame: 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

  2. Vaccine-specific total antibody response after hepatitis A vaccination. In hepatitis A exposed patients, hepatitis B will be used. [ Time Frame: 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


Other Outcome Measures:
  1. Frequency of viral infection [ Time Frame: Up to 1 year ]
    The distribution will be plotted using a histogram. Assessment of influenza vaccine immunogenicity will be performed. GMTs will be calculated at baseline and day 28. Seroconversion (i.e. 4-fold rise in GMT from baseline to day 28) will be determined. Proportions will be binned according to the timing of influenza vaccination: (1) pre-treatment, (2) during radiation, (3) during adjuvant chemotherapy, and (4) post-treatment. Seroconversion proportion within each time point will be compared against known normal using a one proportion test.

  2. Overall survival (OS) [ Time Frame: Date of surgery to death from any cause, assessed up to 14 months ]
    The Kaplan Meier method will be used to estimate OS probability and median time of survival along with 95% confidence interval. Proportional hazards models will be used to assess for associations between mortality and baseline quantitative immunologic values, baseline qualitative immunologic function, and baseline and post-treatment seroconversion to each vaccine (treated as a time dependent variable). All p-values will be reported as two-sided.

  3. Titer of the influenza vaccine-specific IgG antibody [ Time Frame: At 28 days following vaccination with the trivalent inactivated influenza vaccine ]
    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


Biospecimen Retention:   Samples With DNA
peripheral blood


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Adults with primary central nervous system astrocytoma or oligodendroglioma
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02747407


Locations
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United States, North Carolina
Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Roy Strowd Wake Forest University Health Sciences
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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT02747407    
Other Study ID Numbers: IRB00037250
NCI-2016-00472 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CCCWFU 01316 ( Other Identifier: Comprehensive Cancer Center of Wake Forest University )
P30CA012197 ( U.S. NIH Grant/Contract )
First Posted: April 21, 2016    Key Record Dates
Last Update Posted: April 22, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glioma
Astrocytoma
Oligodendroglioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Vaccines
Immunologic Factors
Physiological Effects of Drugs