Vaccine Therapy in Treating Patients Undergoing Surgery for Recurrent Glioblastoma Multiforme

Recurrent Central Nervous System Neoplasm Clinical Trial

Official title:

Recurrent GBM Stem Cell Tumor Amplified RNA Immunotherapy Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00890032
• Other study ID #: Pro00006677
• Secondary ID: R01CA135272P30CA
• Status: Completed
• Phase: Phase 1
• First received: April 28, 2009
• Last updated: October 13, 2016
• Start date: September 2009
• Est. completion date: February 2016

Study information

• Verified date: October 2016
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: February 2016
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms
• Recurrent Central Nervous System Neoplasm

Intervention

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).

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
John Sampson	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility and safety		12 months	Yes
Secondary	Humoral and cellular immune responses		12 months	No