Imiquimod/Brain Tumor Initiating Cell (BTIC) Vaccine in Brain Stem Glioma
This is a pilot/feasibility study. The study design represents a modification of current standard of care for Diffuse Intrinsic Pontine Glioma (DIPG) (5580 cGY involved field radiation), with the final two doses of radiation given at intervals during the vaccination phase of treatment.
Patients between the ages of 3 years and 25 years diagnosed with Diffuse Intrinsic Pontine Glioma (DIPG) will be allowed to participate in the trial. Study enrollment will occur after the completion of conformal radiation therapy to a dose of 5580 cGy and the post radiation therapy (RT) magnetic resonance imaging (MRI) shows no disease progression.
Three patients with glioblastoma multiforme, aged 16 years and older, will be entered first to confirm vaccine safety before enrolling DIPG patients.
Diffuse Intrinsic Pontine Glioma
Biological: Tumor Lysate Vaccine
Radiation: Radiation therapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Imiquimod/BTIC Lysate-Based Vaccine Immunotherapy for Diffuse Intrinsic Pontine Glioma in Children and Young Adults|
- Dose-limiting toxicity [ Time Frame: Within 24 hours of vaccination ] [ Designated as safety issue: Yes ]Determined as Grade 3 or 4 toxicity observation after dosing with BTIC vaccination. Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 4.0) in terms of local, regional and systemic events.
- Time to Tumor Progression [ Time Frame: Study entry through 24 months after treatment ] [ Designated as safety issue: No ]
Imaging will include MRI, SPECT/MRI and perfusion MRI. FDG-PET imaging may be also be used Response criteria: Complete responses (CR) are those in which there is a disappearance of all enhancing tumor or tumor mass on consecutive MRI scans. Patients must be off steroids, and neurologically stable or improved.
Partial responses (PR) are those in which there is a ≥ 50% reduction in the size of the enhancing tumor or tumor mass on consecutive MRI scans. In addition, the patient must be neurologically stable.
- Drop-out rate [ Time Frame: 24 hours, 48 hours and 1 week after each vaccination ] [ Designated as safety issue: Yes ]Treatment feasibility will be based on the drop-out rate in absence of disease progression. Information will be presented in a tabular and descriptive manner
|Study Start Date:||June 2013|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Experimental: DIPG Patients Receiving Vaccine
Patients with diffuse intrinsic pontine glioma (DIPG) receiving radiation therapy, Tumor Lysate Vaccine (dose of 4 x 10^6 cells divided into 2 doses then every 4 weeks for up to 1 year) and Imiquimod (5% Aldara cream at a total dose of 12.5 mg) topically at each site prior to and 24 hours after vaccination.
Biological: Tumor Lysate Vaccine
Vaccination is injected intradermally every 2 weeks for 4 doses, then every 4 weeks for up to 1 year. Patients will receive 1 mg protein divided into 2 doses at two separate subinguinal sites.Drug: Imiquimod
Marketed as 5% Aldara cream topically applied; total of 12.5 mg divided between the two vaccination sites and reapplied at the vaccination sites 24 hours later.
Other Name: Aldara creamRadiation: Radiation therapy
Initial course of radiation therapy is given over 6-7 weeks, 5580 cGy. Additional 180 cGy fractions will be delivered as a single dose on days of 1st and 3rd vaccinations and given according to standard of care at University of Minnesota Medical Center. Total radiation dose will be 5940 cGy.
Vaccine will be produced by the University Of Minnesota Molecular and Cellular Therapeutics Facility using the established brain tumor initiating cell (BTIC) cell line GBM-6 as the antigen source. Vaccine administration will begin at four weeks (week 10) following completion of radiation therapy and will be given every two weeks for four doses. At the time of the 1st and 3rd vaccinations, additional 180 cGy fractions will be delivered in single doses in a novel effort to induce NKG2D ligand upregulation (thereby "sensitizing" residual tumor to lymphocyte attack). The total radiation dose for each patient will be 5940 cGy. Subsequent vaccinations will be given every four weeks and will continue to a maximum of one year from study enrollment, by which time median survival will have passed based on historical data. Imaging will be obtained at study entry (post radiation therapy) and every eight weeks thereafter to eighteen months, after which time the interval between imaging follow-up episodes will be determined by the patient's clinical status. Imaging will include MRI of the brain using our current institutional brain tumor imaging protocol. Imaging will also include SPECT/MRI and perfusion MRI. FDG-PET imaging may be used in certain cases to differentiate tumor necrosis from progression.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01400672
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Christopher Moertel, M.D.||Masonic Cancer Center, University of Minnesota|