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]
- 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
- 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
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
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
After completion of study treatment, patients are followed every 2 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Functional capacity of CD4+,CD25+, CD127- T-regulatory cells
Gordana Vlahovic, MD
United States: Food and Drug Administration
|Duke University Medical Center||Durham, North Carolina 27710|