Clinical Trials /

Trial of Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine

NCT02722512

Description:

The purpose of this study is to determine whether Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine is an feasible and safe treatment for pediatric patients with newly-diagnosed High-Grade Gliomas or recurrent, resectable High-Grade Gliomas and Ependymomas.

Related Conditions:
  • Ependymoma
  • High-Grade Glioma, NOS
  • Malignant Glioma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Trial of Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine
  • Official Title: A Phase I and Feasibility Trial of Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine for Pediatric Patients With Newly Diagnosed Intracranial High Grade Glioma and Recurrent Resectable Intracranial High Grade Glioma and Ependymoma

Clinical Trial IDs

  • ORG STUDY ID: 2016-362
  • NCT ID: NCT02722512

Conditions

  • Glioblastoma Multiforme
  • Astrocytoma, Grade III
  • Anaplastic Ependymoma
  • Clear Cell Ependymoma
  • Ependymoma

Interventions

DrugSynonymsArms
Heat Shock Protein Peptide Complex-96 (HSPPC-96)Newly Diagnosed High Grade Glioma (HGG)

Purpose

The purpose of this study is to determine whether Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine is an feasible and safe treatment for pediatric patients with newly-diagnosed High-Grade Gliomas or recurrent, resectable High-Grade Gliomas and Ependymomas.

Detailed Description

      Immunotherapy for Brain Tumors:

      Although it is usually ineffective alone, it has long been recognized that the immune system
      of tumor bearing hosts (human and animal models) does, indeed, mount an endogenous
      immune-mediated response to tumor. Unfortunately, this immune response alone is not
      sufficient in combating tumor. The balance of immune response and immune regulation often
      mitigates this anti-tumor response. Several mechanisms within tumor-bearing hosts compromise
      the efficacy of this anti-tumor immune response, including low levels of expression of
      co-stimulatory molecules such as the B7 family of immune-regulatory ligands, the tumor's
      local production of immunosuppressive factors and the tumor's ability to over-express
      pro-survival factors thus escaping destruction by the host immune system. However, many have
      hypothesized that if this immune response can be better harnessed and/or magnified, there is
      potential for heightened tumor responses.

      A number of specific observations support the use of immunotherapy to treat brain tumors.
      Data published supports a possible correlation between HIV mediated immunosuppression and
      the development of intracranial glial tumors. Immunosuppression in transplant recipients has
      also been implicated in the development of intracranial glioma. Further supporting this
      hypothesis are documented rare cases of long-term remission of malignant brain tumors
      following significant post-operative infection. These observations have fueled the idea that
      a heightened immune system may confer some protection against intracranial tumors. With this
      in mind, one hypothesis is that successful active immunotherapy for patients with brain
      tumors will require development of a specific peptide or polyvalent vaccines in an effort to
      further stimulate the host's immune system against specific tumor-associated antigens.

      It has been well established that mice can be immunized against syngeneic tumors. Heat shock
      protein-peptide complexes isolated from a specific tumor can been utilized to elicit both
      prophylactic and therapeutic immunity against the specific cancer from which the
      preparations have been isolated. Overexpression of heat shock protein-chaperone complexes
      (HSPPC) in brain tumor cells suggests that HSPPC are a meaningful target antigen for a brain
      tumor vaccine. Moreover, in addition to generating tumor-specific immunity, vaccination with
      heat shock protein peptide complexes in animal models generates therapeutic responses. Since
      an immune response has not been widely evaluated for pediatric brain tumors, this study will
      test the safety and feasibility of producing and administering a vaccine capable of
      generating an autologous, anti-tumor immune response.

      HSPPC-96:

      Heat shock proteins are up-regulated along with tissue-specific chaperone peptides in the
      setting of cellular stress to prevent damage and aggregation of the proteome. Therefore,
      heat shock protein peptide complexes (HSPPC) provide a cytoprotective effect. Overexpression
      of heat shock proteins has been described in malignant glioma and medulloblastoma cells.
      HSPPC-96 is an autologous tumor-derived vaccine that has been under clinical investigation
      for the treatment of a variety of cancer types, including adult high-grade glioma (HGG). It
      is composed of the 96-kilodalton (KDa) heat shock protein, glycoprotein 96 (gp96), attached
      to autologous tumor-derived peptides. The gp96 glycoprotein in HSPPC-96 is a highly
      conserved, abundant, non-polymorphic stress protein found in every cell type of the body.
      Gp96 isolated from normal or tumor tissues is found in complex with peptides that are
      specific to the original tissue. Mouse models have shown that HSPPC-96 confers protective
      immunity only to the tumor from which it is derived and not to genetically distinct tumors
      or normal tissue.

      When injected into the host, HSPPC-96 interacts with antigen presenting cells (APCs) via
      specific receptors. Once internalized by the APCs, the peptides chaperoned by the HSP are
      transferred to major histocompatibility complex (MHC) class I and class II molecules in
      intracellular compartments and eventually expressed at the cell surface. T-cells then
      recognize the MHC-peptide complexes and are stimulated. HSP-peptide complexes are unique in
      their ability to elicit an antigen-specific cytotoxic T-cell response. Additionally, cluster
      of differentiation 4 (CD4+) T cells and natural killer (NK) cells are also recruited adding
      to the tumor-associated immunity.

      Some advantages of heat shock protein-peptide vaccines for immunotherapy are that it elicits
      a cluster of differentiation (CD8+) T cell response in spite of exogenous administration, it
      circumvents the need for identification of T-cell epitopes of individual cancers, and it
      minimizes the possibility of generating epitope variants. Furthermore, heat shock
      protein-peptide complexes have elicited tumor rejection and CD8+ T cell response without
      adjuvant therapies. Heat shock protein-peptide complexes, such as HSPPC-96, can be isolated
      from human tumors, and when injected back into the patient from whom they were isolated, may
      present a unique opportunity to deliver a vaccine specific to that patient.
    

Trial Arms

NameTypeDescriptionInterventions
Newly Diagnosed High Grade Glioma (HGG)ExperimentalHeat Shock Protein Peptide Complex-96 (HSPPC-96) therapy will be given between 0-28 days after the completion of radiation therapy (XRT) AND no more than 60 days from completion of XRT. Vaccine will be given once weekly for 4 weeks. The 4 weeks (28 days) of vaccine administration will be followed by four weeks (28 days) of observation. In patients with sufficient vaccine (on both Arms A and B), a maintenance therapy will be instituted. It will be administered at the same dose the patient was enrolled at and given every 2 weeks until vaccine is exhausted or there is evidence of tumor progression. The first dose of maintenance vaccine should be administered between day 0-14 (and no greater than 28 days) after completion of the 28 days observation period.
    Recurrent HGG and EpendymomaExperimentalOn Arm B, Heat Shock Protein Peptide Complex-96 (HSPPC-96) will be given as soon as possible after tumor resection post-operative recovery and sufficient time for vaccine preparation (typically 0-28 days post-operatively) AND no more than 60 days post-operatively. Vaccine will be given once weekly for 4 weeks. These 4 weeks (28 days) of vaccines will be followed by four weeks (28 days) of observation. In patients with sufficient vaccine, a maintenance therapy will be given. It will be given at the same dose the patient was enrolled at and given every 2 weeks until vaccine is exhausted or there is evidence of tumor progression. The first dose of maintenance vaccine should be given between day 0-14 (and no greater than 28 days) after completion of the 28 days observation period.

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Arm A: Newly Diagnosed High Grade Glioma Tumor
      
                -  Arm B: Recurrent, resectable High Grade Glioma or Ependymoma
      
                -  Stable Neurologic Status
      
                -  Lanksy/Karnofsky score greater than or equal to 50.
      
                -  Adequate Bone Marrow Function (ANC≥ 1000/μL, platelets≥ 100,000/μL transfusion
                   independent, Hemoglobin ≥ 8.0 gm/dL with or without transfusion support)
      
                -  Adequate Liver Function (Bilirubin ≤ 2x institutional normal for age, Alanine
                   transaminase (ALT) ≤ 5x institutional normal for age, Aspartate Aminotransferase
                   (AST) ≤ 5x institutional normal for age)
      
                -  Adequate Renal Function (Normal creatinine for age and/or glomerular filtration rate
                   ≥ 70 mls/min/1.73 m2)
      
                -  Female patients of childbearing potential must have a negative serum or urine
                   pregnancy test
      
              Exclusion Criteria:
      
                -  Patients with unresectable disease are not eligible.
      
                -  Patients with primary spinal cord tumors are not eligible.
      
                -  Patients with metastatic disease are not eligible for Arm A (this does NOT apply to
                   Arm B).
      
                -  Patients with a known allergy to any component of the vaccine or any compounds of
                   similar chemical or biologic composition of the vaccine are not eligible.
      
                -  Patients with known auto-immune disease are excluded.
      
                -  Patients with known immunodeficiency are excluded.
      
                -  Patients with a concurrent malignancy are excluded.
      
                -  Clinically Significant Concurrent Illness
      
                -  Patients receiving any other anticancer or investigational drug
      
                -  Patients with uncontrolled seizure disorders
      
                -  Patients whose central nervous system (CNS) tumor is considered a secondary
                   malignancy from prior therapies
            
      Maximum Eligible Age:21 Years
      Minimum Eligible Age:3 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:The rolling 6 statistical design will be utilized to establish the MTD and RP2D of HSPCC autologous vaccine in children with newly diagnosed high grade glioma (HGG) following focal radiation therapy and in recurrent HGG and ependymoma given alone.
      Time Frame:36 months
      Safety Issue:
      Description:

      Secondary Outcome Measures

      Measure:To estimate the progression-free survival distribution in children with recurrent and resectable HGG treated with HSPPC-96 vaccine therapy alone (Arm B).
      Time Frame:60 months
      Safety Issue:
      Description:
      Measure:To estimate the progression-free survival distribution in children with recurrent and resectable ependymoma treated with HSPPC-96 vaccine therapy alone (Arm B).
      Time Frame:60 months
      Safety Issue:
      Description:
      Measure:To evaluate patient immune responses as measured by intracellular cytokine staining and peripheral blood immune correlates in the above patient groups.
      Time Frame:60 months
      Safety Issue:
      Description:

      Details

      Phase:Phase 1
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Ann & Robert H Lurie Children's Hospital of Chicago

      Last Updated

      July 28, 2016