Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors
DC 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 children with refractory brain tumors. This will result in anti-tumor immunity that will prolong survival of subjects treated and results will be consistent with the outcomes found for subjects treated by HGG Immuno Group investigators. Study treatment will correlate with laboratory evidence of immune activation. Correlative studies will also reveal targets in the immune system which can be exploited to improve response for patients on successor trials.
High Grade Glioma
Biological: Dendritic Cell Vaccine
Biological: Tumor Lysate
Procedure: Punch Biopsy of the Skin
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Dendritic Cell Vaccine Therapy With In Situ Maturation for Pediatric Brain Tumors|
- Number of Subjects Experiencing Adverse Events [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]To demonstrate that dendritic cell vaccine loaded with tumor lysate is feasible and safe in patients diagnosed with brain cancer as children.
- Number of Subjects Experiencing Complete Response or Partial Response according to RECIST Criteria 1.1 [ Time Frame: 36 months ] [ 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 or prolonged progression free survival.
- Measurement levels of Myeloid Derived Suppressor Cells before and after treatment [ Time Frame: 36 months ] [ Designated as safety issue: No ]To demonstrate that treatment with dendritic cell vaccines loaded with tumor lysate injected through imiquimod treated skin cause immune responses that can be measured in subjects.
- Number of Patients with Recurrent Brian Tumor who complete Therapy [ Time Frame: 36 months ] [ Designated as safety issue: No ]To estimate the proportion of patients with recurrent pediatric brain tumors who are able to receive all adminstrations 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: DC Vaccine + Lysate||
Biological: Dendritic Cell Vaccine
Subjects will begin to receive DC vaccination alone, approximately 2 weeks after 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 up to 1.5 mg of tumor lysate, divided into 4 equal doses. 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 Names:Other: 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. The DC and lysate are to be injected in the clinic by the PI or his designee. Subjects will be evaluated 24 hours, and whenever possible, 48 hours after injection for administration site reactions and delayed type hypersensitivity reactions (DTH).
Other Name: AklaraProcedure: Punch Biopsy of the Skin
This procedure is optional
Other Names:Procedure: 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 2 x 1010 mononuclear cells. Each procedure may take 3-5 hours.
Other Name: Pheresis
Please refer to this study by its ClinicalTrials.gov identifier: NCT01902771
|United States, Florida|
|University of Miami||Recruiting|
|Miami, Florida, United States, 33136|
|Contact: John M Goldberg, MD email@example.com|
|Contact: Emil Kamar firstname.lastname@example.org|
|Sub-Investigator: Ofelia Alvarez, MD|
|Sub-Investigator: Martin Andreansky, MD PhD|
|Sub-Investigator: Julio Barredo, MD|
|Sub-Investigator: Sanjiv Bhatis, MD|
|Sub-Investigator: Joanna Davis, MD|
|Sub-Investigator: Cristina Fernandes, MD|
|Sub-Investigator: Antonello Podda, MD|
|Sub-Investigator: John Ragheb, MD|
|Principal Investigator: John M Goldberg, MD|
|Principal Investigator:||John M Goldberg, MD||University of Miami|