Basiliximab in Treating Patients With Newly Diagnosed Glioblastoma Multiforme Undergoing Targeted Immunotherapy and Temozolomide-Caused Lymphopenia
Condition: Malignant Neoplasms Brain
MeSH terms: Glioblastoma; Neoplasms; Lymphopenia
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: 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. 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. Giving these treatments together may kill more tumor cells. Granulocyte
      Macrophage-Colony Stimulating Factor (GM-CSF) is a powerful adjuvant capable of stimulating
      macrophage function, inducing proliferation and maturation of DCs, and is able to enhance
      T-lymphocyte stimulatory function. Intradermal administration of GM-CSF enhances the
      immunization efficacy at the site of administration

      PURPOSE: This clinical trial is studying how well basiliximab works in treating patients with
      newly diagnosed glioblastoma multiforme and temozolomide-caused lymphopenia who are
      undergoing targeted immunotherapy.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To determine if basiliximab inhibits the functional and numeric recovery of T-regulatory
           cells after therapeutic temozolomide (TMZ)-induced lymphopenia in the context of
           vaccinating adult patients with newly diagnosed glioblastoma multiforme (GBM) using
           cytomegalovirus (CMV) pp65-lysosomal-associated membrane protein (LAMP) mRNA-loaded
           dendritic cells (DCs) with GM-CSF in patients who are seropositive and seronegative for
           CMV.

      Secondary

        -  To evaluate the safety of basiliximab in these patients.

        -  To determine if basiliximab enhances the magnitude or character of pp65-specific
           vaccine-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-CD56+ natural killer cells.

        -  To determine if basiliximab in addition to vaccination extends progression-free survival
           compared to historical cohorts.

        -  To characterize immunologic cell infiltrate in recurrent tumors and seek evidence of
           antigen-escape outgrowth.

      OUTLINE: Patients undergo leukapheresis for generation of dendritic cells (DCs) after
      resection. After initial leukapheresis, all patients undergo stereotactic radiotherapy (RT)
      on days 1-5 and concurrent temozolomide (TMZ) IV on days 1-7 for 6.5 weeks in the absence of
      disease progression or unacceptable toxicity.

      Beginning 3 weeks after completion of RT, patients receive TMZ IV on days 1-5. Treatment
      repeats every 28 days for 12 courses in the absence of disease progression or unacceptable
      toxicity. On day 14 ± 2 days of this first cycle of TMZ, patients will receive basiliximab,
      which is 7 days (± 2 days) before DC vaccine #1 and 2 weeks later, a second dose of
      basiliximab will be given, which is also 7 days before vaccine # 2.

      All patients will undergo leukapheresis again for DC generation and immunologic monitoring
      with specific assessment of baseline antigen-specific cellular and humoral immune responses 3
      + 1 weeks after vaccine #3.

      Patients will then be treated monthly with TMZ cycles for a total of 12 cycles . On day 21 ±
      2 days of each TMZ cycle, patients will receive monthly vaccines for a total of 8 vaccines.
      Patients will have blood drawn for immunologic monitoring before basiliximab infusions and
      prior to vaccines 1, 2, 3, and prior to monthly vaccines and then bimonthly through TMZ
      cycles without receiving any other prescribed antitumor therapy until progression.

      After completion of study treatment, patients are followed every 2 months.
    

Intervention name(s): RNA-loaded dendritic cell vaccine; basiliximab
Intervention type(s): Biological; Drug
Intervention description(s): Only one dose of DCs (2 x 10^7) is being assessed.; Basiliximab 20 mg and 40 mg is being assessed depending on dose-cohort enrollment.
Intervention MeSH terms: Basiliximab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult giant cell glioblastoma; adult gliosarcoma