A PHASE I TRIAL OF SURGICAL RESECTION FOLLOWED BY VACCINATION WITH DENDRITIC CELLS PULSED WITH TUMOR LYSATE WITH IMIQUIMOD FOR PATIENTS WITH MALIGNANT GLIOMA (IRB# 19814)
Malignant gliomas are very aggressive and among the most common of brain tumors. A diagnosis carries with it a median survival of approximately 24 months. The current standard treatment of surgical resection followed by radiation therapy and chemotherapy has not substantially prolonged survival and even the few treatment options shown to exhibit small increases in survival primarily benefit certain (i.e., young) patient subpopulations.
Cancer vaccines represent one novel therapy for malignant gliomas. The goal is for the body to recognize the tumor cells are foreign and produce its own response to fight off recurring tumor cells. A promising means of causing an immune response so the body can create this immunity is through the use of dendritic cell (DC) vaccines.
Dendritic cells are a small group of cells contained in everyone's white blood cell population. These cells are responsible for letting the immune system know that something foreign, like bacteria, or a tumor, is in the body. Dendritic cells help the body ward off disease by alerting the immune system. The formulation process of the DC vaccines is described in documents uploaded on the 'Additional Information' page.
Imiquimod in an FDA-approved cream that is an immune response modifier, which will be used off-label in this study. Imiquimod cream (5%, 250 mg) will be self-applied topically by patients to a 4 x 5-cm outlined area of healthy skin overnight on days 1–5 of each cycle. Application and removal times will be recorded in treatment diaries. Dendritic cells will be injected intradermally into the imiquimod-treated site on day 3. Cycles will be repeated every 2 weeks for a total of three injections. This study will examine the effectiveness of using Imiquimod with DC vaccines, as previous studies within the oncology department have studied the effectiveness of DC vaccines. The "IND Application for Off-Label Use of FDA Approved Drugs" contains articles that show that research supports the use of imiquimod with vaccines.
Imiquimod (Aldara, 3M) is one of the better characterized imidazoquinolines and is the only one currently approved for clinical use as a topical ointment. It has been demonstrated to possess antiviral and antitumor properties, and it is approved for the treatment of genital warts. Vaccination studies in animal models have indicated that imidazoquinolines can boost the magnitude and quality of T cell responses. It is considered a Toll-like receptor agonist which controls the activation of dendritic cells.
In humans, it was shown that topical imiquimod treatment may enhance the immunogenicity of a melanoma vaccine. Additionally, injection of immature DCs into imiquimod-pretreated skin lead to DC activation in situ and enhanced migratory capacity to draining lymph nodes in cancer patients. In this study, we test the safety and feasibility of imiquimod in a vaccine against brain cancer to induce a more potent immune response that what has previously been observed.
In prior Phase I and Phase II studies, patients who received chemotherapy following DC demonstrated longer progression free and overall survival than the patients who received DC or chemotherapy alone. The use of DC vaccines is considered investigational and has not yet been approved by the FDA, but we have obtained an IND for use of the vaccines. The purpose of this study is to determine whether after standard therapy of tumor resection surgery followed by DC vaccines with Imiquimod will not only generate (start) an immune response, but will provide longer progression-free survival. Subjects will have clinically indicated resection surgery and will consent to our screening study for vaccine trials (IRB #9225), under which subjects will have their tumor tissue analyzed in order to verify eligibility into this study.
Study procedures include the following: laboratory blood draws, urinalysis at screening, immunological testing, administration of the quality of life questionnaire, neurological exams, MRI testing, leukapherisis for dendritic cells, review of adverse events/concomitant medications.
Patients who were screened and not enrolled in this clinical trial due to screen failure will be notified of the reason for screen failure. Pre HIV counseling and appropriate referral resources will be provided. If the screen failure is due to the positive HIV test, appropriate post HIV counseling will be provided and appropriate referrals will be made. The charts of the patients with screen failures will be destroyed. The patients' charts that will be enrolled in the study will be kept in the locked cabinet in the research office. Patients will be assigned a unique identifying code known only to the research team. Data will be captured by various source documents, or, as necessary, abstracted from hospital medical records by an experienced registered nurse. The electronic data for viral testing will be accessible to research personnel only.
The investigator will be responsible for all research-related costs, and the patient's insurance company will be responsible for costs that are considered standard of care--those that the patient would have regardless if he/she will be participating in a research study such as: surgery, blood tests, clinic visits and MRI scans.
John Yu, MD
Director, Brain Tumor Center
Download PDF Dendritic Cell Vaccine with Imiquimod Trial