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Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma

Primary Purpose

Giant Cell Glioblastoma, Glioblastoma, Gliosarcoma

Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Malignant Glioma Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccine
Temozolomide
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Giant Cell Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Willing and capable of undergoing apheresis for collection of mononuclear cells
  • Histologically confirmed GBM (grade 4 astrocytoma) NOTE: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) may be included, primitive neuroectodermal tumor (PNET) variants are excluded; grade 4 oligodendrogliomas or oligoastrocytomas are specifically excluded
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Absolute neutrophil count (ANC) >= 1500 / uL
  • Platelets (PLT) >= 100,000 / uL
  • Hemoglobin (HgB) >= 9.0 g/dL
  • Total bilirubin =< 1.5 x upper normal limit (UNL)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x UNL
  • Creatinine =< 1 x UNL
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Ability to understand and willingness to sign a written informed consent
  • Willing to return to Mayo Clinic Rochester for follow-up
  • Willing to provide tissue and blood samples for mandatory correlative research purposes
  • Fixed or decreasing dose of corticosteroids (or no corticosteroids) >= 7 days prior to registration
  • Completed standard external beam radiation with temozolomide
  • Achieved a gross total or sub-total resection at time of surgery

Exclusion Criteria:

  • Current or prior treatment for this cancer with immunotherapy and/or any other investigational agents

  • Any of the following

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), hepatitis B (HepB), or hepatitis C (HepC) positive
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • History of other malignancy including treated lower grade gliomas; EXCEPTIONS: non-melanotic skin cancer, carcinoma-in-situ of the cervix, or lower grade glioma that has never been treated previously; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
  • History of myocardial infarction =< 180 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Active infection =< 5 days prior to registration or fever > 38 degrees Celsius (C) on day of registration
  • History of tuberculosis or positive purified protein derivative (PPD) test
  • Inability or unwillingness to have magnetic resonance imaging (MRI) scans performed (e.g. cardiac pacemaker-dependent)

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (vaccine therapy and temozolomide)

Arm Description

COURSE 1: Patients receive temozolomide PO daily on days 1-5. COURSES 2-3: Patients receive temozolomide PO daily on days 1-5 and malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 1, 3, and 5. COURSES 4-6: Patients receive temozolomide PO daily on days 1-5 and malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on day 1. COURSES 7-12: Patients receive malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Incidence of significant toxicity, defined as grade 3 or higher adverse event that is possibly, probably, or definitely related to treatment measured using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Incidence of significant toxicity will be estimated by the number of patients with significant toxicity divided by the total number of evaluable patients.

Secondary Outcome Measures

Change in immunologic correlates
Change in immunologic correlates before and after vaccination treatment will be evaluated and summarized both quantitatively and graphically. Spearman rank correlation coefficient will be used to assess the correlations between baseline levels as well as between changes before and after treatment in these immunologic markers.
Clinical benefit rate
The clinical benefit rate will be estimated by the number of patients with an objective status of stable disease (SD) for at least 12 months or an objective status of CR or PR at any time divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true clinical benefit rate will be calculated.
Duration of response
Duration of response will be summarized descriptively.
Overall response rate
The overall response rate will be estimated by the number of patients with an objective status of complete response (CR) or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Time to response
Time to response will be summarized descriptively.

Full Information

First Posted
October 4, 2013
Last Updated
November 11, 2022
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01957956
Brief Title
Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma
Official Title
Pilot Clinical Trial of Allogeneic Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccination in Newly Diagnosed Glioblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 11, 2013 (Actual)
Primary Completion Date
November 16, 2016 (Actual)
Study Completion Date
November 15, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This pilot clinical trial studies vaccine therapy and temozolomide in treating patients with newly diagnosed glioblastoma. Vaccines made from a person's white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vaccine therapy and temozolomide may be an effective treatment for glioblastoma.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the safety and feasibility of adjuvant temozolomide plus combined allogeneic tumor primary tumor culture lysate / autologous dendritic cell (DC) vaccination (malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine) in newly diagnosed glioblastoma patients following surgical debulking and external beam radiation therapy with concurrent temozolomide. SECONDARY OBJECTIVES: I. To document survival and progression-free survival in newly diagnosed glioblastoma patients receiving adjuvant temozolomide plus allogeneic tumor primary tumor culture lysate / autologous DC vaccination to historical data. TERTIARY OBJECTIVES: I. Determine the ability of allogeneic tumor primary tumor culture lysate / autologous DC vaccine to generate multiple tumor-associated antigens (TAA)-specific immune responses in newly diagnosed glioblastoma multiforme (GBM) patients. II. Assess the relationship between ability tumor induce TAA-specific immune responses and evidence of immunosuppression (peripheral blood immunophenotyping by flow cytometry) following allogeneic tumor primary tumor culture lysate / autologous DC vaccine in newly diagnosed GBM patients. III. Assess the relationship between efficacy endpoints (survival, progression-free survival, tumor response) and tumor-associated antigen immune response following combined autologous or allogeneic tumor lysate / DC vaccination and adjuvant temozolomide. IV. Assess the relationship between efficacy endpoints (survival, progression-free survival, tumor response) and evidence of immunosuppression at baseline and over time with combined autologous or allogeneic tumor lysate / DC vaccination and adjuvant temozolomide. OUTLINE: COURSE 1: Patients receive temozolomide orally (PO) daily on days 1-5. COURSES 2-3: Patients receive temozolomide PO daily on days 1-5 and malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine intradermally (ID) on days 1, 3, and 5. COURSES 4-6: Patients receive temozolomide PO daily on days 1-5 and malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on day 1. COURSES 7-12: Patients receive malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Giant Cell Glioblastoma, Glioblastoma, Gliosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (vaccine therapy and temozolomide)
Arm Type
Experimental
Arm Description
COURSE 1: Patients receive temozolomide PO daily on days 1-5. COURSES 2-3: Patients receive temozolomide PO daily on days 1-5 and malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 1, 3, and 5. COURSES 4-6: Patients receive temozolomide PO daily on days 1-5 and malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on day 1. COURSES 7-12: Patients receive malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
Malignant Glioma Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccine
Intervention Description
Given ID
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Incidence of significant toxicity, defined as grade 3 or higher adverse event that is possibly, probably, or definitely related to treatment measured using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Description
Incidence of significant toxicity will be estimated by the number of patients with significant toxicity divided by the total number of evaluable patients.
Time Frame
Up to 84 days
Secondary Outcome Measure Information:
Title
Change in immunologic correlates
Description
Change in immunologic correlates before and after vaccination treatment will be evaluated and summarized both quantitatively and graphically. Spearman rank correlation coefficient will be used to assess the correlations between baseline levels as well as between changes before and after treatment in these immunologic markers.
Time Frame
Baseline to up to 5 years
Title
Clinical benefit rate
Description
The clinical benefit rate will be estimated by the number of patients with an objective status of stable disease (SD) for at least 12 months or an objective status of CR or PR at any time divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true clinical benefit rate will be calculated.
Time Frame
Up to 5 years
Title
Duration of response
Description
Duration of response will be summarized descriptively.
Time Frame
Up to 5 years
Title
Overall response rate
Description
The overall response rate will be estimated by the number of patients with an objective status of complete response (CR) or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Time Frame
Up to 5 years
Title
Time to response
Description
Time to response will be summarized descriptively.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Willing and capable of undergoing apheresis for collection of mononuclear cells Histologically confirmed GBM (grade 4 astrocytoma) NOTE: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) may be included, primitive neuroectodermal tumor (PNET) variants are excluded; grade 4 oligodendrogliomas or oligoastrocytomas are specifically excluded Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 Absolute neutrophil count (ANC) >= 1500 / uL Platelets (PLT) >= 100,000 / uL Hemoglobin (HgB) >= 9.0 g/dL Total bilirubin =< 1.5 x upper normal limit (UNL) Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x UNL Creatinine =< 1 x UNL Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only Ability to understand and willingness to sign a written informed consent Willing to return to Mayo Clinic Rochester for follow-up Willing to provide tissue and blood samples for mandatory correlative research purposes Fixed or decreasing dose of corticosteroids (or no corticosteroids) >= 7 days prior to registration Completed standard external beam radiation with temozolomide Achieved a gross total or sub-total resection at time of surgery Exclusion Criteria: Current or prior treatment for this cancer with immunotherapy and/or any other investigational agents Any of the following Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), hepatitis B (HepB), or hepatitis C (HepC) positive Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements History of other malignancy including treated lower grade gliomas; EXCEPTIONS: non-melanotic skin cancer, carcinoma-in-situ of the cervix, or lower grade glioma that has never been treated previously; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer History of myocardial infarction =< 180 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias Active infection =< 5 days prior to registration or fever > 38 degrees Celsius (C) on day of registration History of tuberculosis or positive purified protein derivative (PPD) test Inability or unwillingness to have magnetic resonance imaging (MRI) scans performed (e.g. cardiac pacemaker-dependent)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ian Parney
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma

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