Clinical Trials /

Vaccine Therapy in Treating Patients With Recurrent Glioblastoma

NCT03360708

Description:

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.

Related Conditions:
  • Glioblastoma
  • Gliosarcoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: MC1772
  • SECONDARY ID: NCI-2017-02159
  • SECONDARY ID: MC1772
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03360708

Conditions

  • Giant Cell Glioblastoma
  • Recurrent Glioblastoma
  • Recurrent Gliosarcoma

Interventions

DrugSynonymsArms
Malignant Glioma Tumor Lysate-Pulsed Autologous Dendritic Cell VaccineTreatment (vaccine therapy)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (vaccine therapy)ExperimentalPatients 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.
  • Malignant Glioma Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccine

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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Time Frame:Up to 5 years
Safety Issue:
Description: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

Measure:Clinical benefit rate
Time Frame:Up to 5 years
Safety Issue:
Description: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.
Measure:Duration of response
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
Safety Issue:
Description:Duration of response will be summarized descriptively.
Measure:Feasibility
Time Frame:Up to 5 years
Safety Issue:
Description: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.
Measure:Overall response rate
Time Frame:Up to 5 years
Safety Issue:
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.
Measure:Overall survival
Time Frame:Time from study registration to progression and death due to any cause, assessed up to 5 years
Safety Issue:
Description:
Measure:Progression-free survival
Time Frame:Time from study registration to progression and death due to any cause, assessed up to 5 years
Safety Issue:
Description:
Measure:Time to response
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
Safety Issue:
Description:Time to response will be summarized descriptively.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

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