Vaccine Therapy in Treating Patients Undergoing Surgery for Recurrent Glioblastoma Multiforme

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
John Sampson, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00890032
First received: April 28, 2009
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention Phase
Recurrent Central Nervous System Neoplasm
Biological: BTSC mRNA-loaded DCs
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Recurrent GBM Stem Cell Tumor Amplified RNA Immunotherapy Trial

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Feasibility and safety [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Humoral and cellular immune responses [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: September 2009
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BTSC mRNA-loaded DCs
BTSC mRNA-loaded DCs administered intradermally weekly for first 3 vaccines, then monthly until progression or withdrawal.
Biological: 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).

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00890032

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
John Sampson
Investigators
Principal Investigator: Gordana Vlahovic, MD Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: John Sampson, Professor of Neurosurgery, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00890032     History of Changes
Other Study ID Numbers: Pro00006677, R01CA135272, P30CA014236, CDR0000630701
Study First Received: April 28, 2009
Last Updated: June 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
adult astrocytoma
recurrent adult brain tumor

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Glioblastoma
Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on October 22, 2014