Clinical Trials /

Vaccine Therapy for the Treatment of Newly Diagnosed Glioblastoma Multiforme

NCT02465268

Description:

The purpose of this research study is to determine if an investigational dendritic cell vaccine, called pp65 DC, is effective for the treatment of a specific type of brain tumor called glioblastoma (GBM) when given with stronger doses of routine chemotherapy.

Related Conditions:
  • Glioblastoma
  • Malignant Supratentorial Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Vaccine Therapy for the Treatment of Newly Diagnosed Glioblastoma Multiforme
  • Official Title: A Phase II Randomized, Blinded, and Placebo-controlled Trial of CMV RNA-Pulsed Dendritic Cells With Tetanus-Diphtheria Toxoid Vaccine in Patients With Newly-Diagnosed Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: IRB201400697-N
  • SECONDARY ID: R01CA175517
  • SECONDARY ID: OCR14127
  • NCT ID: NCT02465268

Conditions

  • Glioblastoma Multiforme
  • Glioblastoma
  • Malignant Glioma
  • Astrocytoma, Grade IV
  • GBM

Interventions

DrugSynonymsArms
pp65-shLAMP DC with GM-CSFpp65-shLAMP mRNA DCs with GM-CSFpp65-shLAMP DC with GM-CSF and Td
unpulsed PBMC and salinePeripheral Blood Mononuclear Cellsunpulsed PBMC and Saline
TdTetanus and Diphtheria Toxoidpp65-shLAMP DC with GM-CSF and Td
SalineNormal Salineunpulsed PBMC and Saline
pp65-flLAMP DC with GM-CSFpp65-flLAMP mRNA DCs with GM-CSFpp65-flLAMP DC with GM-CSF and Td

Purpose

The purpose of this research study is to determine if an investigational dendritic cell vaccine, called pp65 DC, is effective for the treatment of a specific type of brain tumor called glioblastoma (GBM) when given with stronger doses of routine chemotherapy.

Detailed Description

      Dendritic cells (DC) are involved in activating, or turning-on, your body's immune system.
      Your immune system helps guard your body from germs, viruses, and other threats. Although
      dendritic cells are very strong, the number of them in the body is not high enough to cause a
      powerful immune response; therefore, more DC are made in a laboratory with cells collected
      from an individual's blood.

      In this study, we will make a vaccine that we hope will educate immune cells to target the
      pp65 antigen, a type of immune marker in GBM, thus resulting in what we call the pp65 DC
      vaccine. Use of a vaccine that activates your immune system is a type of immunotherapy. It is
      hoped that by giving the pp65 DC vaccine as a shot under the skin, the immune system will be
      activated to attack tumor cells in the brain while leaving normal cells alone.

      To see if the pp65 DC vaccine is effective for the treatment of GBM, subjects will be
      assigned to different treatment groups. Two groups of subjects will receive the pp65 DC
      vaccine and one group will receive a placebo.
    

Trial Arms

NameTypeDescriptionInterventions
pp65-shLAMP DC with GM-CSF and TdExperimentalGiven under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
  • pp65-shLAMP DC with GM-CSF
  • Td
pp65-flLAMP DC with GM-CSF and TdExperimentalGiven under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
  • Td
  • pp65-flLAMP DC with GM-CSF
unpulsed PBMC and SalinePlacebo ComparatorGiven under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.
  • unpulsed PBMC and saline
  • Saline

Eligibility Criteria

        Abbreviated Inclusion Criteria:

        To be assessed at study enrollment prior to standard of care chemo-radiation therapy:

          -  Age ≥ 18 years.

          -  Histopathologically proven newly-diagnosed de novo GBM (WHO Grade IV glioma)

          -  The tumor must have a supratentorial component.

          -  Must have undergone definitive surgical resection of tumor with less than
             approximately 3cm x 3cm residual enhancing tumor as product of longest perpendicular
             planes by MRI.

          -  Recovery from the effects of surgery, postoperative infection, and other
             complications.

          -  Diagnostic contrast-enhanced MRI or CT scan of the brain preoperatively and
             postoperatively.

          -  Karnofsky Performance Status of ≥ 70.

          -  Signed informed consent.

          -  For females of childbearing potential, negative serum pregnancy test.

          -  Women of childbearing potential and male participants must be willing to practice
             adequate contraception throughout the study and for at least 24 weeks after the last
             dose of study drug.

        To be assessed prior to initiation of adjuvant TMZ:

          -  Must have completed RT (targeted total dose of 59.4-60.0 Gy over ≤ 7 weeks) and
             concomitant TMZ (targeted dose of 75mg/m2/d for ≤ 49 days) therapy without significant
             toxicity that persisted over 4 weeks.

          -  History & physical with neurologic examination prior to initiation of adjuvant TMZ.

          -  For patients receiving steroids, daily dose must be ≤ 4 mg.

          -  CBC with differential with adequate bone marrow function.

          -  Adequate renal function.

          -  Adequate hepatic function.

        Abbreviated Exclusion Criteria:

        To be verified in order to randomize subject:

          -  Prior invasive malignancy unless disease free for ≥ 3 years.

          -  Metastases detected below the tentorium or beyond the cranial vault and leptomeningeal
             involvement.

          -  Recurrent or multifocal malignant gliomas.

          -  HIV, Hepatitis B, or Hepatitis C seropositive.

          -  Known active infection or immunosuppressive disease.

          -  Prior chemotherapy or radiosensitizers (including Gliadel wafers) for cancers of the
             head and neck region.

          -  Prior radiotherapy to the head or neck, resulting in overlap of radiation fields.

          -  Severe, active co-morbidity.

          -  Pregnancy or women of childbearing potential and men who are sexually active and not
             willing/able to use medically acceptable forms of contraception for the entire study
             period.

          -  Pregnant or lactating women.

          -  Prior allergic reaction to temozolomide, GM-CSF or Td.

          -  Prior history of brachial neuritis or Guillain-Barré syndrome.

          -  Patients treated on any other therapeutic clinical protocols within 30 days prior to
             study entry.

        To be assessed prior to initiation of adjuvant TMZ:

          -  Did not start radiation therapy and temozolomide within 7 weeks of surgery.

          -  Progression of disease as defined by modified RANO criteria.

          -  More than 45 days after completion of radiation therapy and temozolomide
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in median overall survival
Time Frame:From date of randomization until the date of death, assessed up to 24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Changes in immune response
Time Frame:Change between baseline and vaccine #3, assessed up to 4 weeks
Safety Issue:
Description:Parameters include ELISPOT for evaluation of cellular immune responses is a sensitive detection assay for evaluation of antigen specific cytokine producing T cells
Measure:Change in progression-free survival
Time Frame:From randomization until first documentation of either disease progression or recurrence assessed up to 24 months
Safety Issue:
Description:
Measure:Changes in immune response
Time Frame:Change between baseline and vaccine #3, assessed up to 4 weeks
Safety Issue:
Description:Parameters include peak antibody titers to the CMV pp65, reported as humoral response to the specific antigens.
Measure:Changes in immune response
Time Frame:Change between baseline and vaccine #3, assessed up to 4 weeks
Safety Issue:
Description:Parameters include Cytokine Bead Array analysis to detect multiple cytokines secreted by lymphocytes after in vitro stimulation with specific and control antigens, examine the spectrum of Type 0,1,2, and 3 cytokines secreted by T cells after stimulation with overlapping peptides spanning CMV pp65, PHA, and control peptides
Measure:Changes in immune response
Time Frame:Change between baseline and vaccine #3, assessed up to 4 weeks
Safety Issue:
Description:Parameters include cytokine flow cytometric analysis which involves the rapid early detection and analysis of the production of IFN, TNF, and IL-2 prior to cellular secretion following antigen-specific stimulation in vitro as determined by CFC

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Florida

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