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Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01957956
Recruitment Status : Active, not recruiting
First Posted : October 8, 2013
Last Update Posted : September 27, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE October 4, 2013
First Posted Date  ICMJE October 8, 2013
Last Update Posted Date September 27, 2019
Actual Study Start Date  ICMJE November 11, 2013
Actual Primary Completion Date November 16, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2013)
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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2015)
  • Change in immunologic correlates [ Time Frame: 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 [ Time Frame: 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.
  • Duration of response [ Time Frame: Up to 5 years ]
    Duration of response will be summarized descriptively.
  • Overall response rate [ Time Frame: 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 [ Time Frame: Up to 5 years ]
    Time to response will be summarized descriptively.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2013)
  • Overall response rate [ Time Frame: 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.
  • Clinical benefit rate [ Time Frame: 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.
  • Time to response [ Time Frame: Up to 5 years ]
    Time to response will be summarized descriptively.
  • Duration of response [ Time Frame: Up to 5 years ]
    Duration of response will be summarized descriptively.
  • Change in immunologic correlates [ Time Frame: 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma
Official Title  ICMJE Pilot Clinical Trial of Allogeneic Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccination in Newly Diagnosed Glioblastoma
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Giant Cell Glioblastoma
  • Glioblastoma
  • Gliosarcoma
Intervention  ICMJE
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Malignant Glioma Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccine
    Given ID
  • Drug: Temozolomide
    Given PO
    Other Names:
    • 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
Study Arms  ICMJE Experimental: Treatment (vaccine therapy and 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.

Interventions:
  • Other: Laboratory Biomarker Analysis
  • Biological: Malignant Glioma Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccine
  • Drug: Temozolomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 17, 2017)
21
Original Estimated Enrollment  ICMJE
 (submitted: October 4, 2013)
10
Estimated Study Completion Date  ICMJE November 15, 2020
Actual Primary Completion Date November 16, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01957956
Other Study ID Numbers  ICMJE MC1272
NCI-2013-01743 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1272 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Ian Parney Mayo Clinic
PRS Account Mayo Clinic
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP