Vaccine Therapy in Treating Patients Undergoing Surgery for Recurrent Glioblastoma Multiforme

NCT ID: NCT00890032

Last Updated: 2016-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2016-02-29

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.

Conditions

Recurrent Central Nervous System Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BTSC mRNA-loaded DCs

BTSC mRNA-loaded DCs administered intradermally weekly for first 3 vaccines, then monthly until progression or withdrawal.

Group Type: EXPERIMENTAL

BTSC mRNA-loaded DCs

Intervention Type: BIOLOGICAL

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).

Interventions

BTSC 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).

Intervention Type: BIOLOGICAL

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

John Sampson

OTHER

Sponsor Role: lead

Responsible Party

John Sampson

Professor of Neurosurgery

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Gordana Vlahovic, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

R01CA135272

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014236

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000630701

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00006677

Identifier Type: -

Identifier Source: org_study_id