search
Back to results

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

Primary Purpose

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

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tumor Lysate Vaccine
Imiquimod
Sponsored by
Frank Lieberman
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for High Risk WHO Grade II Glioma focused on measuring Glioma, Vaccine, Immunotherapy, WHO Grade II

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Pittsburgh Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

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).

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.

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.

Outcomes

Primary Outcome Measures

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)
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.

Secondary Outcome Measures

Full Information

First Posted
August 30, 2012
Last Updated
February 20, 2020
Sponsor
Frank Lieberman
Collaborators
University of Minnesota
search

1. Study Identification

Unique Protocol Identification Number
NCT01678352
Brief Title
Imiquimod and Tumor Lysate Vaccine Immunotherapy in Adults With High Risk or Recurrent Grade II Gliomas
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
November 8, 2017 (Actual)
Study Completion Date
November 8, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Frank Lieberman
Collaborators
University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High Risk WHO Grade II Glioma, Recurrent/Post-Chemotherapy WHO Grade II Glioma
Keywords
Glioma, Vaccine, Immunotherapy, WHO Grade II

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
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).
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Tumor Lysate Vaccine
Intervention Description
Cohort 1 Cohort 2 Cohort 3
Intervention Type
Drug
Intervention Name(s)
Imiquimod
Other Intervention Name(s)
Aldara
Intervention Description
Cohort 1 Cohort 2 Cohort 3
Primary Outcome Measure Information:
Title
Dose limiting toxicity (DLT)
Description
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)
Time Frame
Two Years
Title
Induction of BTIC Lysate-specific T-cell response
Description
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.
Time Frame
Two Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Lieberman, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs