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

NCT01678352 | Completed Early Phase 1 DMC

• 1 other identifier: 11-136
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Glioma; Vaccine; Immunotherapy; WHO Grade II

Outcome Measures

Primary Outcomes (2)

• 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: 1. . Grade 3-5 vaccine related allergic reaction 2. . 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 3. . Grade 2 -5 autoimmune reactions (such as hypothyroidism)

  Two Years

• 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

Study Arms (3)

Cohort 1

EXPERIMENTAL

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; Drug: Imiquimod

Cohort 2

EXPERIMENTAL

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; Drug: Imiquimod

Cohort 3

EXPERIMENTAL

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; Drug: Imiquimod

Interventions

Tumor Lysate Vaccine BIOLOGICAL

Cohort 1 Cohort 2 Cohort 3

Cohort 1; Cohort 2; Cohort 3

Imiquimod DRUG

Cohort 1 Cohort 2 Cohort 3

Also known as: Aldara

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Frank Lieberman: lead
• University of Minnesota: collaborator

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Glioma; Lymphoma, Follicular

Interventions

Imiquimod

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Frank Lieberman, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 30, 2012
• First Posted: September 5, 2012
• Study Start: October 1, 2012
• Primary Completion: November 8, 2017
• Study Completion: November 8, 2018
• Last Updated: February 24, 2020

Record last verified: 2020-02

Locations

US (1)