Vaccine Therapy in Treating Patients Undergoing Surgery for Recurrent Glioblastoma Multiforme

Phase 1

Completed

• Conditions: Recurrent Central Nervous System Neoplasm
• Interventions: Biological: BTSC mRNA-loaded DCs

• Registration Number: NCT00890032
• Lead Sponsor: John Sampson

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2009-04-28
• Study First Submitted QC: 2009-04-28
• Study First Posted: 2009-04-29
• Study Start: 2009-09
• Primary Completion: 2014-10
• Study Completion: 2016-02
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-13
• Last Update Posted: 2016-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Feasibility and safety	12 months

Secondary Outcome Measures

Name	Time	Method
Humoral and cellular immune responses	12 months

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States