Clinical trial NCT00890032: Vaccine Therapy in Treating Patients Undergoing Surgery for Recurrent Glioblastoma Multiforme
Official title: Recurrent GBM Stem Cell Tumor Amplified RNA Immunotherapy Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Recurrent Central Nervous System Neoplasm
Keywords: adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
adult astrocytoma
recurrent adult brain tumor
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-04-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 Exclusion Criteria

Subjects meeting any of the following criteria are ineligible for study entry:

* Inadequately controlled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 100 mmHg)
* Prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* History of myocardial infarction or unstable angina within 6 months prior to enrollment
* History of stroke or transient ischemic attack within 6 months prior to enrollment
* Significant vascular disease (e.g. aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) (within 6 months prior to enrollment)
* History of hemoptysis (\> or = 1/2 teaspoon of bright red blood per episode) within 28 days prior to enrollment
* Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrollment
* Serious, non-healing wound, active ulcer or untreated bone fracture
* Proteinuria as defined by \> +1 on urinalysis dipstick
* Known hypersensitivity to any component of Avastin
* Pregnant (positive pregnancy test) or lactation

Primary outcomes:
measure: Feasibility and safety
timeFrame: 12 months
Secondary outcomes:
measure: Humoral and cellular immune responses
timeFrame: 12 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Gordana Vlahovic, MD
role: PRINCIPAL_INVESTIGATOR
References: