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Vaccine Therapy in Treating Patients With Recurrent Glioblastoma

Primary Purpose

Giant Cell Glioblastoma, Recurrent Glioblastoma, Recurrent Gliosarcoma

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Laboratory Biomarker Analysis

Malignant Glioma Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccine

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:

First or second recurrence of previously histologically confirmed glioblastoma (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
Prior craniotomy and gross total or sub-total resection of tumor at this recurrence NOTE: biopsy of this recurrence alone without attempt at resection does not meet this inclusion criteria (i.e. craniotomy and resection is still required).
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
Absolute neutrophil count (ANC) >= 1500/uL
Monocytes >= 300/uL
Platelets (PLT) >= 100,000/uL
Hemoglobin (HgB) >= 9.0 g/dL
Total bilirubin =< 1.5 x upper limit of normal (ULN)
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN
Creatinine =< 1.5 x ULN
Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
Ability to understand and willingness to sign written informed consent
Willing to return to Mayo Clinic in Rochester, Minnesota 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

Exclusion Criteria:

Prior treatment
- Current or prior treatment for this cancer with immunotherapy and/or any other investigational agents
- Surgery =< 2 weeks prior to registration
- Radiotherapy =< 12 weeks prior to registration
- Treatment with bevacizumab or any cytotoxic chemotherapy =< 8 weeks prior to registration
Any of the following
- Pregnant persons
- Nursing persons
- Persons 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 other than glioma
- EXCEPTIONS: non-melanotic skin cancer, carcinoma-in-situ of the cervix, or systemic cancer that has been in documented remission for > 10 years
- 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) within 5 days prior to 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)

Arm Description

Patients receive malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 1, 3, and 5 of courses 2 and 3, and on day 1 of subsequent courses. Treatment with malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine repeats every 21 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Incidence of significant toxicity, defined as a dose limiting toxicity (DLT) that is possibly, probably, or definitely related to treatment as assessed by 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

Clinical benefit rate

The clinical benefit rate will be estimated by the number of patients with an overall survival for at least 6 months after enrollment 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.

Feasibility

The feasibility of the regimen will be estimated by the number of patients who received at least one dose of dendritic cell (DC) injection divided by the total number of patients who received leukapheresis in that arm.

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.

Overall survival

Progression-free survival

Time to response

Time to response will be summarized descriptively.

Full Information

NCT ID

NCT03360708

First Posted

November 28, 2017

Last Updated

June 27, 2023

Sponsor

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT03360708

Brief Title

Vaccine Therapy in Treating Patients With Recurrent Glioblastoma

Official Title

Pilot Clinical Trial of Allogeneic Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccination in Recurrent Glioblastoma

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

November 27, 2013 (Actual)

Primary Completion Date

June 2, 2021 (Actual)

Study Completion Date

June 2, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This pilot early phase I trial studies the side effects of vaccine therapy in treating patients with glioblastoma that has come back. Vaccines made from a person's white blood cells mixed with tumor proteins from another person's glioblastoma tumors may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy may work better in treating patients with glioblastoma.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the safety and feasibility of malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine (autologous dendritic cell [DC] / allogeneic glioblastoma multiforme [GBM] culture lysate vaccination) in glioblastoma patients at first or second recurrence. SECONDARY OBJECTIVES: I. To document survival and progression-free survival in glioblastoma patients at first or second recurrence receiving autologous DC / allogeneic GBM culture lysate vaccination and compared to historical data. TERTIARY OBJECTIVES: I. Determine the ability of autologous DC / GBM culture lysate vaccination to generate multiple tumor-associated antigen (TAA)-specific immune responses in GBM patients at first or second recurrence. II. Assess the relationship between ability tumor induced TAA-specific immune responses and evidence of immunosuppression (peripheral blood immunophenotyping by flow cytometry) following autologous DC / allogeneic GBM culture lysate vaccination in GBM patients at first or second recurrence. III. Assess the relationship between efficacy endpoints (survival, progression-free survival, tumor response) and tumor-associated antigen immune response following autologous DC / allogeneic GBM culture lysate vaccination IV. Assess the relationship between efficacy endpoints (survival, progression-free survival, tumor response) and evidence of immunosuppression at baseline and over time with autologous DC / allogeneic GBM culture lysate vaccination. OUTLINE: Patients receive malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine intradermally (ID) on days 1, 3, and 5 of courses 2 and 3, and on day 1 of subsequent courses. Treatment with malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine repeats every 21 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Giant Cell Glioblastoma, Recurrent Glioblastoma, Recurrent 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

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (vaccine therapy)

Arm Type

Experimental

Arm Description

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

Primary Outcome Measure Information:

Title

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 5 years

Secondary Outcome Measure Information:

Title

Clinical benefit rate

Description

Time Frame

Up to 5 years

Title

Duration of response

Description

Duration of response will be summarized descriptively.

Time Frame

Date at which the patient?s objective status is first noted to be either a CR or PR to the earliest date progression is documented, assessed up to 5 years

Title

Feasibility

Description

Time Frame

Up to 5 years

Title

Overall response rate

Description

Time Frame

Up to 5 years

Title

Overall survival

Time Frame

Time from study registration to progression and death due to any cause, assessed up to 5 years

Title

Progression-free survival

Time Frame

Time from study registration to progression and death due to any cause, assessed up to 5 years

Title

Time to response

Description

Time to response will be summarized descriptively.

Time Frame

Date of initiation of vaccination treatment to the date at which the patient?s objective status is first noted to be either a CR or PR, assessed up to 5 years

Other Pre-specified Outcome Measures:

Title

Change in immunologic correlates

Description

Change in immunologic correlates before and after vaccination treatment will be evaluated and summarized both quantitatively and graphically. Will use Spearman rank correlation coefficient to assess the correlations between baseline levels as well as between changes before and after treatment in these immunologic markers. In addition, these immunologic markers will be correlated with cancer and treatment-related outcomes (e.g. response, toxicities). Relationships will also be explored graphically using scatter plots.

Time Frame

Baseline up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: First or second recurrence of previously histologically confirmed glioblastoma (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 Prior craniotomy and gross total or sub-total resection of tumor at this recurrence NOTE: biopsy of this recurrence alone without attempt at resection does not meet this inclusion criteria (i.e. craniotomy and resection is still required). Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 Absolute neutrophil count (ANC) >= 1500/uL Monocytes >= 300/uL Platelets (PLT) >= 100,000/uL Hemoglobin (HgB) >= 9.0 g/dL Total bilirubin =< 1.5 x upper limit of normal (ULN) Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN Creatinine =< 1.5 x ULN Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only Ability to understand and willingness to sign written informed consent Willing to return to Mayo Clinic in Rochester, Minnesota 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 Exclusion Criteria: Prior treatment Current or prior treatment for this cancer with immunotherapy and/or any other investigational agents Surgery =< 2 weeks prior to registration Radiotherapy =< 12 weeks prior to registration Treatment with bevacizumab or any cytotoxic chemotherapy =< 8 weeks prior to registration Any of the following Pregnant persons Nursing persons Persons 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 other than glioma EXCEPTIONS: non-melanotic skin cancer, carcinoma-in-situ of the cervix, or systemic cancer that has been in documented remission for > 10 years 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) within 5 days prior to 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 in Treating Patients With Recurrent Glioblastoma

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