Vaccine Therapy in Treating Patients Undergoing Surgery for Recurrent Glioblastoma Multiforme

John Sampson

Status and phase

Completed

Phase 1

Conditions

Recurrent Central Nervous System Neoplasm

Treatments

Biological: BTSC mRNA-loaded DCs

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00890032

Pro00006677

R01CA135272 (U.S. NIH Grant/Contract)

CDR0000630701 (Other Identifier)

P30CA014236 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Full 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.

Enrollment

50 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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