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

High Risk WHO Grade II Glioma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01678352
• Other study ID #: 11-136
• Status: Completed
• Phase: Early Phase 1
• Start date: October 2012
• Est. completion date: November 8, 2018

Study information

• Verified date: February 2020
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: November 8, 2018
• Est. primary completion date: November 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioma
• High Risk WHO Grade II Glioma
• Recurrent/Post-Chemotherapy WHO Grade II Glioma

Intervention

Biological:
• Tumor Lysate Vaccine
Cohort 1 Cohort 2 Cohort 3

Drug:
• Imiquimod
Cohort 1 Cohort 2 Cohort 3

Locations

Country	Name	City	State
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Frank Lieberman	University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity (DLT)	The incidence and severity of adverse events associated with the vaccine regime will be assessed according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE), as follows: . Grade 3-5 vaccine related allergic reaction; . Grade 3-5 organ toxicity (cardiac, dermatologic (excluding localized skin reaction), gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due to the underlying malignancy and occurring within 28 days of vaccination and of any length in duration; . Grade 2 -5 autoimmune reactions (such as hypothyroidism)	Two Years
Primary	Induction of BTIC Lysate-specific T-cell response	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.	Two Years