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

NCT ID: NCT01678352

Last Updated: 2020-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2018-11-08

Brief 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.

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

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Tumor Lysate Vaccine

Intervention Type: BIOLOGICAL

Cohort 1 Cohort 2 Cohort 3

Imiquimod

Intervention Type: DRUG

Cohort 1 Cohort 2 Cohort 3

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.

Group Type: EXPERIMENTAL

Tumor Lysate Vaccine

Intervention Type: BIOLOGICAL

Cohort 1 Cohort 2 Cohort 3

Imiquimod

Intervention Type: DRUG

Cohort 1 Cohort 2 Cohort 3

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.

Group Type: EXPERIMENTAL

Tumor Lysate Vaccine

Intervention Type: BIOLOGICAL

Cohort 1 Cohort 2 Cohort 3

Imiquimod

Intervention Type: DRUG

Cohort 1 Cohort 2 Cohort 3

Interventions

Tumor Lysate Vaccine

Cohort 1 Cohort 2 Cohort 3

Intervention Type: BIOLOGICAL

Imiquimod

Cohort 1 Cohort 2 Cohort 3

Intervention Type: DRUG

Other Intervention Names

Aldara

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: collaborator

Frank Lieberman

OTHER

Sponsor Role: lead

Responsible Party

Frank Lieberman

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Frank Lieberman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

11-136

Identifier Type: -

Identifier Source: org_study_id