Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma

Early Phase 1

Completed

• Conditions: Gliosarcoma; Glioblastoma; Giant Cell Glioblastoma
• Interventions: Other: Laboratory Biomarker Analysis; Biological: Malignant Glioma Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccine; Drug: Temozolomide

• Registration Number: NCT01957956
• Lead Sponsor: Mayo Clinic

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2013-10-04
• Study First Submitted QC: 2013-10-04
• Study First Posted: 2013-10-08
• Study Start: 2013-11-11
• Primary Completion: 2016-11-16
• Study Completion: 2016-11-16
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-16
• Last Update Posted: 2023-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (vaccine therapy and temozolomide)	Laboratory Biomarker Analysis	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.
Treatment (vaccine therapy and temozolomide)	Malignant Glioma Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccine	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.
Treatment (vaccine therapy and temozolomide)	Temozolomide	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.

Primary Outcome Measures

Name	Time	Method
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	Up to 84 days	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

Name	Time	Method
Duration of response	Up to 5 years	Duration of response will be summarized descriptively.
Overall response rate	Up to 5 years	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	Up to 5 years	Time to response will be summarized descriptively.
Change in immunologic correlates	Baseline to up to 5 years	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	Up to 5 years	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.

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States