Imiquimod/Brain Tumor Initiating Cell (BTIC) Vaccine in Brain Stem Glioma

Phase 1

Terminated

• Conditions: Diffuse Intrinsic Pontine Glioma
• Interventions: Biological: Tumor Lysate Vaccine; Drug: Imiquimod; Radiation: Radiation therapy

• Registration Number: NCT01400672
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2011-07-19
• Study First Submitted QC: 2011-07-21
• Study First Posted: 2011-07-22
• Study Start: 2012-07-17
• Primary Completion: 2016-03-07
• Study Completion: 2018-10-08
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-16
• Last Update Posted: 2020-03-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

Not provided

Exclusion Criteria

• Pregnant or breast-feeding. Pregnancy testing will be performed on all menstruating females within 14 days prior to study enrollment.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
• Currently receiving any chemotherapy, investigational agents or registration on another therapy based trial or received chemotherapy with radiation therapy
• History of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immunosuppression)
• Any isolated laboratory abnormality suggestive of a serious autoimmune disease
• Any conditions that could potentially alter immune function (AIDS, multiple sclerosis, diabetes, renal failure)
• Receiving ongoing treatment with immunosuppressive drugs, excluding those patients requiring dexamethasone for treatment of tumor-related edema

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DIPG Patients Receiving Vaccine	Tumor Lysate 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.
DIPG Patients Receiving Vaccine	Radiation therapy	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.
DIPG Patients Receiving Vaccine	Imiquimod	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.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity	Within 24 hours of vaccination	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.

Secondary Outcome Measures

Name	Time	Method
Drop-out rate	24 hours, 48 hours and 1 week after each vaccination	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
Time to Tumor Progression	Study entry through 24 months after treatment	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.

Trial Locations

Locations (1)

Masonic Cancer Center, University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States