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Imiquimod/BTIC Lysate-Based Vaccine Immunotherapy for Diffuse Intrinsic Pontine Glioma in Children and Young Adults

Phase 1
3 Years
Open (Enrolling)
Diffuse Intrinsic Pontine Glioma, Glioblastoma Multiforme, Adult Glioblastoma

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Trial Information

Imiquimod/BTIC Lysate-Based Vaccine Immunotherapy for Diffuse Intrinsic Pontine Glioma in Children and Young Adults

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.

Inclusion Criteria

Inclusion Criteria - GBM patients only (enrollment plan 1):

- Histologically confirmed glioblastoma multiforme (GBM) World Health Organization
(WHO) grade III-IV with recurrent or progressive disease after standard therapy

- Age 16 years or older

Inclusion Criteria - DIPG patients only (enrollment plan 2 and 3):

- Diagnosis of diffuse intrinsic pontine glioma (DIPG) by magnetic resonance imaging
(MRI). Because the safety of biopsy of DIPG has not been firmly established, biopsy
will not be required for study enrollment.

- Completion of standard radiation therapy (not to exceed 5580 cGy) with a post
radiation therapy (RT) MRI that shows no disease progression when compared with
pre-RT MRI. All patients must be treated with Intensity Modulated Radiation Therapy
(IMRT) or an equivalent conformal technique. The clinical target volume will be
defined as the gross tumor volume (full extent of tumor visible on MRI) plus 1 cm
margin. Patients from an outside institution who are referred after the start of
radiation therapy may complete initial radiation therapy at their home institution as
long as dosage guidelines are met and the total dose does not exceed 5580 cGy at the
time of study registration.

- Able to begin vaccination 4 weeks (+ or - 1 week) of completion of standard radiation

- Age 3 years and older Inclusion Criteria - all patients regardless of diagnosis

- Clinically stable and off or on low dose (no more than 0.1 mg/kg/day, maximum of 4
mg/day dexamethasone) corticosteroid for at least 1 week prior to study enrollment

- Lansky (0-15 years) or Karnofsky (16 years or older) performance score of ≥ 60

- Adequate organ function within 14 days of study registration including the following:

- Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count
(ANC) ≥ 1.0 x 10^9/L, platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 8 g/dL

- Hepatic: - Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age and SGPT
(ALT) ≤ 2.5 x upper limit of normal (ULN) for age

- Renal: Normal serum creatinine for age or creatinine clearance >60 ml/min/1.73

- Sexually active females of child bearing potential must agree to use adequate
contraception (diaphragm, birth control pills, injections, intrauterine device [IUD],
surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration
of the vaccination period. Sexually active males must agree to use barrier
contraceptive for the duration of the vaccination period.

- Voluntary written informed consent must be obtained from all patients (if of assent
age) and their parents or legal guardians before performance of any study-related
procedure not part of normal medical care, with the understanding that consent may be
withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria - all patients:

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity

Outcome Description:

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.

Outcome Time Frame:

Within 24 hours of vaccination

Safety Issue:


Principal Investigator

Christopher Moertel, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Food and Drug Administration

Study ID:




Start Date:

July 2012

Completion Date:

July 2014

Related Keywords:

  • Diffuse Intrinsic Pontine Glioma
  • Glioblastoma Multiforme
  • Adult Glioblastoma
  • Diffuse intrinsic pontine glioma
  • glioblastoma multiforme
  • adult glioblastoma
  • Glioblastoma
  • Glioma
  • Pontine Glioma



Masonic Cancer Center, University of MinnesotaMinneapolis, Minnesota  55455