Daclizumab in Treating Patients With Newly Diagnosed Glioblastoma Multiforme Undergoing Targeted Immunotherapy and Temozolomide-Caused Lymphopenia
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.
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.
Malignant Neoplasms Brain
Biological: RNA-loaded dendritic cell vaccine
Biological: cytomegalovirus pp65-specific cytotoxic T lymphocytes
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||REGULATory T-Cell Inhibition With Daclizumab (Zenapax®) During Recovery From Therapeutic Temozolomide-induced Lymphopenia During Antitumor Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed Glioblastoma Multiforme [REGULATe]|
- Functional capacity of CD4+,CD25+, CD127- T-regulatory cells [ Time Frame: 26 months ] [ Designated as safety issue: No ]
- Safety [ Time Frame: 26 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2007|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Experimental: CMV pp65-LAMP mRNA-loaded DC vaccination
Basiliximab will be safe in combination with CMV pp65-LAMP mRNA-loaded DC vaccination and ALT
Biological: RNA-loaded dendritic cell vaccine
Only one dose of DCs (2 x 10^7) is being assessed.Biological: cytomegalovirus pp65-specific cytotoxic T lymphocytes
Only one dose of ALT (3 x 10^7/Kg) is being assessed.Drug: basiliximab
Only one dose of basiliximab (20 mg) is being assessed.Drug: imiquimod
For imiquimod pretreatment the site will be applied 3 times every other day with the last application being 6-24 hours before vaccination. One packet of imiquimod 5% cream with 12.5 mg of imiquimod per 0.25g cream will be used for each application.
- 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 autolymphocyte therapy (ALT) in patients who are seropositive and seronegative for CMV.
- 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 and ALT extends progression-free survival compared to historical cohorts.
- To assess the differential ability of indium In 111-labeled DCs to track to the inguinal lymph nodes under different skin-preparative conditions.
- 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) and autolymphocyte therapy (ALT) within 4 weeks 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 6 courses in the absence of disease progression or unacceptable toxicity. Beginning on day 21 of the first course of TMZ, patients receive pp65-LAMP mRNA-loaded mature DCs every 2 weeks for 3 vaccinations. Concurrently with the first DC vaccination, patients receive ALT IV over 15 minutes and basiliximab IV over 30 minutes.
On day 21 of the second course of post-radiation TMZ, patients receive indium In 111-labeled DCs (fourth vaccination) and randomly assigned skin preparations (unpulsed DCs vs imiquimod cream applied to the vaccination site 6-24 hours before vaccination). Single-photon emission computed tomography (SPECT) images are used to quantitate migration to the inguinal lymph nodes.
After completion of study treatment, patients are followed every 2 months.
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Gordana Vlahovic, MD||Duke University|