Recurrent Central Nervous System Neoplasm
Conditions
Keywords
adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, adult astrocytoma, recurrent adult brain tumor
Brief summary
RATIONALE: Vaccines made from a person's tumor cells and dendritic cells may help the body build an effective immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side effects of vaccine therapy in treating patients undergoing surgery for recurrent glioblastoma multiforme (GBM).
Detailed description
OBJECTIVES: Primary * To evaluate the feasibility and safety of an autologous brain tumor stem cell messenger ribonucleic acid (mRNA)-loaded dendritic cell vaccine in adult patients with recurrent glioblastoma multiforme. Secondary * To assess humoral and cellular immune responses to vaccination. * To compare the proportion of vaccinated patients alive at 6 months from the time of surgery for recurrent tumor with matched historical cohorts. OUTLINE: Patients undergo surgical resection of tumor. Tumor tissue samples are collected to isolate brain tumor stem cells (BTSCs) and for extraction and amplification of BTSC-specific mRNA. Within 4 weeks after surgical resection, patients undergo leukapheresis over 4 hours to generate dendritic cells (DCs). Patients also undergo leukapheresis at 1 week after the third vaccination and then at least every 3 months as needed for generation of additional DCs. Patients receive autologous BTSC mRNA-loaded DC vaccine intradermally once weekly for 3 weeks and then once monthly in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.
Interventions
BIOLOGICALBTSC mRNA-loaded DCs
An escalating total dose of BTSC mRNA-loaded DCs (2x10\^6, 5x10\^6, and 2x10\^7 per vaccination) will be evaluated for purpose of establishing a maximum tolerated dose (MTD) and a dose-limiting toxicity (DLT).
Sponsors
National Cancer Institute (NCI)
John Sampson
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 years of age * First recurrence of GBM (WHO Grade IV glioma or astrocytoma) in surgically accessible areas with prior histologic diagnosis of GBM * No known contraindications to receiving Avastin * Karnofsky Performance Status (KPS) of \> 70% * Radiation Therapy (RT) with ≥ 45 Gy tumor dose, completed ≥ 8 weeks prior to study entry
Exclusion criteria
* Contrast-enhancing tumor component crossing the midline, multi-focal tumor, or tumor dissemination (subependymal or leptomeningeal) * Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment * Pregnant or need to breast feed during the study period (Negative beta-human chorionic gonadotropin (HCG) test required), or unable to maintain use of contraception while on study * Active infection requiring treatment or an unexplained febrile (\> 101.5 degrees F) illness * Known immunosuppressive disease, autoimmune disease or human immunodeficiency virus infection, Hepatitis B or Hepatitis C * Unstable or severe intercurrent medical conditions such as severe heart (New York Association Class 3 or 4) or lung (FEV1 \< 50%) disease, uncontrolled diabetes mellitus * Prior brachytherapy, carmustine wafer therapy, radiolabeled monoclonal antibodies, or stereotactic radiosurgery * Prior inguinal lymph node dissection Avastin-Specific
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility and safety | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Humoral and cellular immune responses | 12 months |
Countries
United States
Outcome results
None listed