Dendritic Cell Vaccine For Malignant Glioma and Glioblastoma Multiforme in Adult and Pediatric Subjects
Dendritic Cell vaccine manufactured and partially matured using our standard operating procedures, developed in collaboration with the HGG Immuno Group, then administered through imiquimod treated skin will be safe and feasible in patients with high grade glioma. This will result in anti-tumor immunity that will prolong survival of subjects treated. Study treatment will correlate with laboratory evidence of immune activation.
High Grade Glioma
Biological: Dendritic Cell Vaccine
Biological: Tumor Lysate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Dendritic Cell Vaccine For Malignant Glioma and Glioblastoma Multiforme in Adult and Pediatric Subjects|
- Number of Subjects Experiencing Adverse Events [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]To demonstrate that dendritic cell vaccine loaded with tumor lysate is feasible and safe in pediatric and adult subjects with relapsed high grade glioma or glioblastoma multiforme treated at the University of Miami. This will be done in the same manner as that of our HGG Immuno collaborators and will use imiquimod topically as the final step in maturing the vaccine product. The number of subjects experiencing adverse events will be characterized by type, grade and attribution to treatment as well as by time of onset in relation to the day of Dendritic Cell vaccination. We will report the number and percent of unacceptable adverse events among subjects
- Measurement levels of immune response before and after treatment [ Time Frame: 5 years ] [ Designated as safety issue: No ]To demonstrate that treatment with dendritic cell vaccines loaded with tumor lysate created injected through imiquimod treated skin cause immune responses that can be measured in subjects
- Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]To demonstrate that treatment with dendritic cell vaccines loaded with tumor lysate created and matured through the in vivo process cause benefit for subjects in the form of prolonged survival. Measured from the date of enrollment on study to the recorded date of death
- Progression-Free Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]To demonstrate that treatment with dendritic cell vaccines loaded with tumor lysate created and matured through the in vivo process cause benefit for subjects in the form of prolonged progression free survival. Measured from the date of enrollment on study to the earliest occurrence of progression, relapse or death from any cause
- Comparison of clinical outcomes to pre-treatment clinical variables measured in other DC imiquimod clinical studies. [ Time Frame: 5 years ] [ Designated as safety issue: No ]To demonstrate if the clinical parameters associated with outcomes described for patients on other DC / imiquimod protocols hold for subjects treated on our study.
- Number of subjects with recurrent glioma who are able to receive all administrations of the Dendritic Cell Vaccine [ Time Frame: 5 years ] [ Designated as safety issue: No ]Number of subjects with recurrent glioma who are able to receive all administrations of DC and the proportion who are able to receive all administrations of DC and lysate.
|Study Start Date:||July 2013|
|Estimated Primary Completion Date:||July 2018 (Final data collection date for primary outcome measure)|
|Experimental: Dendritic Cell Vaccine||
Biological: Dendritic Cell Vaccine
Subjects will begin to receive DC vaccination alone, when recovered from pheresis and continue weekly for a total of four vaccinations. The vaccination with loaded DC will be given in the clinic as an intradermal injection in the upper arms. DC will be delivered with each vaccination in 6 separate syringes (3 syringe injections per arm within the area of approximately the size of a silver dollar spaced approximately equally) alternating between anterior and posterior deltoid. For subjects who are missing limbs (e.g., arms), the injection sites will be rotated between the arms and thighs (alternating anterior and lateral thigh) with anterior and posterior deltoid. For subjects who do not have an accessible deltoid, both legs will be used. All injections with DC or lysate will be done after topical treatment with imiquimod to the site of injection the day prior to injection, which will then be applied for two nights after the injection to the sites.
Other Name: DC VaccineBiological: Tumor Lysate
After completion of DC vaccination course, lysate of tumor will be administered during weeks 8, 12, 16, and 28. Lysate dose will be 1.5 mg of tumor lysate, divided into 2 syringes with a total volume of 0.4 mL per injection. If there is not enough lysate to produce 1.5 mg per dose, then the remaining lysate will be divided into four equal aliquots. All lysate will be injected into one (1) arm intradermally in alternating arms/thigh as above within an area of approximately the size of a silver dollar spaced approximately equally. Lysate will be injected from one syringe for each administration. Clinical examination after study treatment ends will be required every three (3) months + 14 days.
Other Name: Lysate of TumorOther: Imiquimod
Subjects will self-apply imiquimod one night before and each night for two nights after the scheduled administration of DC or lysate. Investigator will instruct the subject to apply a thin layer of imiquimod on the selected area (approximately the area of a silver dollar) of both arms,or thigh. Subjects are advised to rinse the selected area with water (where imiquimod is applied) the morning after application. Subjects will be given a medication diary when supplied with imiquimod in which they will record both the time of application of the imiquimod, and the time of rinse of the imiquimod.
Other Name: AldaraProcedure: Leukapheresis
Patients enrolled in the study will undergo a leukapheresis procedure performed to collect peripheral blood mononuclear cells. Leukapheresis will be performed using a continuous flow blood cell separator (COBE Spectra, Caridian BCT, Lakewood, CO). This instrument relies on density gradient centrifugation to collect mononuclear cells from the apheresis patients. Leukapheresis is typically performed through a central venous catheter (a catheter inserted into one of the larger veins in the body) or through a peripheral intravenous catheter that may be placed the day of the procedure. An anticoagulant is added to circulate blood to prevent clotting during the procedure. In this study, leukapheresis will be performed to collect 1.5 x 10^9 mononuclear cells. Each procedure may take 3-5 hours.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01808820
|United States, Florida|
|University of Miami||Recruiting|
|Miami, Florida, United States, 33136|
|Contact: John Goldberg, MD firstname.lastname@example.org|
|Contact: Emil Kamar email@example.com|
|Principal Investigator: John Goldberg, MD|
|Sub-Investigator: Ofelia Alvarez, MD|
|Sub-Investigator: Martin Andreasky, MD, PhD|
|Sub-Investigator: Antonello Podda, MD|
|Sub-Investigator: Julio Barredo, MD|
|Sub-Investigator: Joanna Davis, MD|
|Sub-Investigator: Deborah Heros, MD|
|Sub-Investigator: Edward D Ziga, MD|
|Sub-Investigator: Sherry Shariatmadar, MD|
|Sub-Investigator: Fernando Corrales, MD|
|Principal Investigator:||John Goldberg, MD||University of Miami|