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Imiquimod and Tumor Lysate Vaccine Immunotherapy in Adults With High Risk or Recurrent Grade II Gliomas

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by University of Pittsburgh
University of Minnesota - Clinical and Translational Science Institute
Information provided by (Responsible Party):
University of Pittsburgh Identifier:
First received: August 30, 2012
Last updated: January 12, 2016
Last verified: January 2016
This is a pilot study of a vaccination regime that is designed to efficiently induce anti-tumor T-cell responses in patients with WHO grade II glioma. The proposed regime with BTIC Lysate in combination with imiquimod, an FDA-approved immune response modifier will induce potent anti-glioma immune response with minimal or no toxicity.

Condition Intervention Phase
High Risk WHO Grade II Glioma
Recurrent/Post-Chemotherapy WHO Grade II Glioma
Biological: Tumor Lysate Vaccine
Drug: Imiquimod
Early Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study to Evaluate the Effects of Imiquimod and Tumor Lysate Vaccine Immunotherapy for Adults With High Risk or Recurrent/Post-Chemotherapy WHO Grade II Gliomas

Resource links provided by NLM:

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Safety [ Time Frame: Two Years ]
    The incidence and severity of adverse events associated with the vaccine regime will be assessed, with an early stopping rule based on the frequency of Dose Limiting Toxicity (DLT).

  • Induction of BTIC Lysate-specific T-cell response [ Time Frame: Two Years ]
    We will determine the response rate and magnitude of immune response in post-vaccine peripheral blood mononuclear cells (PBMC) against the BTIC Lysate in response to this form of vaccine, using IFN-enzyme-linked immuno-spot (ELISPOT) assays.

Estimated Enrollment: 27
Study Start Date: October 2012
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Patients must have undergone surgery or biopsy alone (no postoperative radiation or chemotherapy) and have a baseline MRI scan (within 4 weeks of the first vaccine) that shows stable disease or regression (no progression from the initial surgery/biopsy).
Biological: Tumor Lysate Vaccine
Cohort 1 Cohort 2 Cohort 3
Drug: Imiquimod
Cohort 1 Cohort 2 Cohort 3
Other Name: Aldara
Experimental: Cohort 2
Patients received surgery or biopsy and radiation therapy (RT) (including fractionated external beam radiation therapy and/or stereotactic radiosurgery), which was completed ≥ 6 months prior to enrollment, and have a baseline MRI scan within 4 weeks prior to the first vaccine that shows stable disease or regression.
Biological: Tumor Lysate Vaccine
Cohort 1 Cohort 2 Cohort 3
Drug: Imiquimod
Cohort 1 Cohort 2 Cohort 3
Other Name: Aldara
Experimental: Cohort 3
Patients with recurrent WHO grade 2 glioma may have received prior external beam radiotherapy and/or chemotherapy. Patients with stable WHO grade 2 glioma must have had prior chemotherapy (at least one cycle of Temozolomide or PCV-based chemotherapy). With regard to the prior therapy in Cohort 3, patients may have had treatment for no more than 2 prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy) or observation of stable disease. The intent therefore is that patients may have had 3 prior therapies (initial therapy and treatment for 2 relapses). If the patient had a surgical resection for relapsed disease, and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse.
Biological: Tumor Lysate Vaccine
Cohort 1 Cohort 2 Cohort 3
Drug: Imiquimod
Cohort 1 Cohort 2 Cohort 3
Other Name: Aldara

Detailed Description:

To determine the response rate and magnitude of CD8+ T-cell responses against the Imiquimod/BTIC lysate-based vaccines in post-vaccine PBMC using IFN- ELISPOT. ELISPOT assays indicate functional status of the antigen-specific T cells as cytokine-expression, and we are particularly interested in Type-1 (i.e. IFN expressing) T cell response. Therefore, IFN ELISPOT will be used as the primary assay for the immunological endpoint.

Using flow-cytometry, we will also evaluate the numbers of lymphocyte subsets such as CD4+ T cells, CD4+/Foxp3+ regulatory T cells in an exploratory manner. In addition, in participants who undergo surgical debulking of the progressing tumor, if the tumor tissue is available, infiltration of antigen-specific CTLs will be evaluated by flow cytometry of tumor-infiltrating lymphocytes with the Imiquimod/BTIC lysate-based vaccine-targeted GAA specific MHC-tetramers. In addition, serological responses will be evaluated with flow-cytometry of BTIC cells as well as western blotting. These plans (in this paragraph) are immunological evaluations; however, do not compose the primary endpoints due to their exploratory nature.

We will determine whether it is safe to administer Imiquimod/BTIC lysate-based vaccines in patients with grade II gliomas. Endpoints will therefore include incidence and severity of adverse events, using standard criteria as well as close clinical follow-up as would be performed normally in this group of participants following vaccinations. All reported or observed toxicities and adverse events at all clinic visits will be graded, documented and reported according to a standard toxicity table, the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Cohort 1 and 2: Age ≥18 year old with histologically diagnosed World Health Organization (WHO) grade II astrocytoma or oligoastrocytoma with "high-risk" factors - defined as:

    • age ≥ 40 with any extent resection;
    • age 18-39 with incomplete resection (post-op MRI showing >1cm residual disease, based on the maximum dimension of residual T2 or fluid-attenuated inversion-recovery [FLAIR] abnormality from the edge of the surgical cavity either laterally, anteroposteriorly, or superoinferiorly) or
    • age 18-39 with neurosurgeon-defined gross total resection (GTR) but the tumor size is ≥ 4 cm (the maximum preoperative tumor diameter, based on the axial and/or coronal T2 or FLAIR MR images) Cohort 3: Age ≥18 year old with histologically diagnosed WHO grade II glioma with recurrence
    • Karnofsky performance status ≥ 60%
    • Clinically stable and off corticosteroids for at least 4 weeks prior to study enrollment
    • Adequate organ function within 14 days of study registration including:
    • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1.0 x 109/L, platelets ≥100 x 109/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 or creatinine clearance ≥60 ml/min/1.73 m2

Exclusion Criteria:

  • History of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) that required systemic immunosuppression therapy and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immunosuppression)
  • Any isolated laboratory abnormality suggestive of a serious autoimmune disease (e.g. hypothyroidism)
  • 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
  • Currently receiving any investigational agents or registration on another therapy based trial
  • Pregnant or lactating
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01678352

Contact: Melinda Vargas-Jaffee, RN 412-235-1320
Contact: Sarah Anderson, RN 412-958-0728

United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Melinda Vargas-Jaffe, RN    412-235-1320   
Principal Investigator: Frank Lieberman, MD         
Sub-Investigator: Jan Drappatz, MD         
Sponsors and Collaborators
University of Pittsburgh
University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Frank Lieberman, MD University of Pittsburgh
  More Information

Responsible Party: University of Pittsburgh Identifier: NCT01678352     History of Changes
Other Study ID Numbers: 11-136
Study First Received: August 30, 2012
Last Updated: January 12, 2016

Keywords provided by University of Pittsburgh:
WHO Grade II

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antineoplastic Agents
Interferon Inducers processed this record on May 25, 2017