Chemotherapy, Radiation Therapy, and Vaccine Therapy With Basiliximab in Treating Patients With Glioblastoma Multiforme That Has Been Removed by Surgery
Condition: Malignant Neoplasms of Brain
MeSH terms: Glioblastoma; Neoplasms; Brain Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: 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.
      Radiation therapy uses high-energy x-rays to kill tumor cells. Vaccines may help the body
      build an effective immune response to kill tumor cells. Monoclonal antibodies, such as
      basiliximab, can block tumor growth in different ways. Some block the ability of tumor cells
      to grow and spread. Others find tumor cells and help kill them or carry tumor-killing
      substances to them. It is not yet known whether giving chemotherapy, radiation therapy, and
      vaccine therapy together with basiliximab is a more effective treatment for glioblastoma
      multiforme than chemotherapy, radiation therapy, and vaccine therapy alone.

      PURPOSE: This randomized phase I trial is studying the side effects and best way to give
      chemotherapy and radiation therapy followed by vaccine therapy with basiliximab in treating
      patients with glioblastoma multiforme that has been removed by surgery.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To determine if basiliximab inhibits the functional and numeric recovery of T-regulatory
           cells (Tregs) after therapeutic temozolomide (TMZ)-induced lymphopenia in the context of
           vaccinating adult patients with newly diagnosed glioblastoma multiforme (GBM) using
           PEPvIII-keyhole limpet hemocyanin (KLH).

      Secondary

        -  To evaluate the safety of basiliximab in the context of vaccinating adult patients with
           newly diagnosed GBM using PEP-3-KLH conjugate vaccine during recovery from therapeutic
           TMZ-induced lymphopenia.

        -  To determine if basiliximab enhances the magnitude or character of PEPvIII-KLH-induced
           cellular or humoral immune responses, inhibits or enhances activation-induced cell
           death, or induces immunologic or clinical evidence of autoimmunity.

        -  To determine if basiliximab enhances the magnitude or character of PEPvIII-KLH-induced
           cellular or humoral immune responses, inhibits or enhances activation-induced cell
           death, or induces immunologic or clinical evidence of autoimmunity.

        -  To determine if basiliximab alters the phenotype (CD56-expression), cytokine secretion
           profile, or cytotoxicity of CD3-negative CD56-positive natural killer cells.

        -  To determine if basiliximab, in addition to vaccination, extend progression-free
           survival compared to historical cohorts.

        -  To characterize immunologic cell infiltrate in recurrent tumors and seek evidence of
           antigen escape outgrowth.

      OUTLINE:

        -  Leukapheresis: Patients undergo leukapheresis over 2-4 hours for immunologic monitoring.

        -  Concurrent standard adjuvant chemoradiotherapy: Patients receive external-beam
           radiotherapy once daily, 5 days a week, over 6-7 weeks (33 fractions) and concurrent
           temozolomide by mouth 7 days a week for up to 49 days beginning on the first day and
           continuing until the last day of radiotherapy.

        -  Temozolomide and PEP-3-KLH conjugate vaccine: Approximately 3 weeks after completion of
           radiotherapy, patients receive temozolomide by mouth on days 1-21, or on days 1-5
           depending on their treating neuro-oncologist, basiliximab IV over 30 minutes on day 21,
           and PEP-3-KLH conjugate vaccine intradermally on days 21, 35, and 49.

      Patients then receive a second course of temozolomide by mouth on days 1-21 or days 1-5,
      depending on their treating neuro-oncologist. Treatment with temozolomide repeats every 4
      weeks for 5 additional courses. Patients also receive PEP-3-KLH conjugate vaccine on day 21
      of each remaining temozolomide course. Patients then receive the vaccine monthly until
      disease progression.

      Patients undergo blood sample collection periodically for laboratory studies.

      After completion of study therapy, patients are followed periodically.
    

Intervention name(s): PEP-3-KLH conjugate vaccine; daclizumab; temozolomide; placebo; PEP-3-KLH
Intervention type(s): Biological; Biological; Drug; Other; Biological
Intervention description(s): Given intradermally; Given IV; Given by mouth.; Given IV; Basiliximab 20 mg IV over 30 minutes with PEP-3-KLH vaccine # 1 only.
Other intervention name(s): CDX-110; EGFRvIII-KLH
Intervention MeSH terms: Temozolomide; Daclizumab
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; adult high grade glioma