A Bi-Institutional Pilot Study to Evaluate the Effects of Vaccinations With HLA-A2-Restricted Glioma Antigen-Peptides in Combination With Poly-ICLC for Adults With WHO Grade II Low-Grade Gliomas

Ian F. Pollack, M.D.2 sites in 1 country13 target enrollmentJanuary 2009

ConditionsAstrocytoma Oligo-Astrocytoma Glioma

Overview

Phase: Early Phase 1
Intervention: Not specified
Conditions: Astrocytoma
Sponsor: Ian F. Pollack, M.D.
Enrollment: 13
Locations: 2
Primary Endpoint: 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 Regimen Limiting Toxicity (RLT).
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a pilot vaccine study in adults with either WHO grade II astrocytoma, oligoastrocytoma or oligodendroglioma. The purpose of this study is test the safety and efficacy of an experimental tumor vaccine made from peptides and Montanide ISA-51 in combination with the study drug Poly-ICLC.

Poly-ICLC, manufactured by Oncovir, Inc., has already been received and generally well tolerated by subjects in earlier studies and has been shown to decrease the size of brain tumors in some cases.

The immunological and safety data will be used to decide whether a larger study of clinical efficacy is warranted in each of two patient cohorts.

Detailed Description

All patients on the study will be followed for a minimum of 2 years, so that the actual 2-year overall survival (OS) and progression-free survival (PFS) rates can be determined in an exploratory manner.

Registry

clinicaltrials.gov

Start Date

January 2009

End Date

July 2015

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Ian F. Pollack, M.D.

Responsible Party

Sponsor Investigator

Principal Investigator

Ian F. Pollack, M.D.

Chief, Pediatric Neurosurgery

University of Pittsburgh

Eligibility Criteria

Inclusion Criteria

•Participants must have documented pathological diagnosis of a WHO grade II astrocytoma or oligoastrocytoma or oligodendroglioma (see also the 4th bullet for oligodendroglioma).
•HLA-A2 positive based on flow cytometry.
•There will be 2 cohorts of patients based on whether patients have received prior RT. Cohort 1: patients must have undergone surgery or biopsy alone ≤16 weeks prior to study entry (no postoperative radiation or chemotherapy). 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 of the first vaccine) that shows stable disease or regression.
•For oligodendroglioma, at least one of the following three conditions has to be met: 1) age ≥ 40 with any extent resection; 2) age 18-39 with incomplete resection (post-op MRI showing \> 1cm residual disease, based on the maximum dimension of residual T2 or FLAIR abnormality from the edge of the surgical cavity either laterally, antero-posteriorly, or supero-inferiorly) or 3) age 18-39 with neurosurgeon-defined 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). Participants must be ≥ 18 years old because the safety of each therapeutic component has not been established in children.
•All participants must sign an informed consent document indicating that they are aware of the investigational nature of this study.
•Participants must have a Karnofsky performance status of \> 60 (Appendix I).
•Documented negative serum beta HCG for female participants of child-bearing age. Males and females must agree, in the consent form, to use effective birth control methods during the course of vaccination. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the peptide based vaccine and poly-ICLC, breastfeeding should be discontinued if the mother is treated in this study.
•Participants must be free of systemic infection
•Participants with adequate organ function as measured by white blood count ≥ 2500/mm3; lymphocytes ≥ 800/mm3; platelets ≥ 100,000/mm3, hemoglobin ≥ 10.0 g/dL, AST, ALT, GGT, LDH, alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin greater than or equal to 2.0 mg/dL, and serum creatinine within 1.5 X upper limit of normal limit. Coagulation tests PT and PTT have to be within normal limits.

Exclusion Criteria

•Presence of cranial or spinal leptomeningeal metastatic disease.
•Prior chemotherapy or anti-glioma therapy of any type other than radiation therapy (see 3.1.3)
•Concurrent treatment or medications including:
•Radiation therapy
•Chemotherapy
•Interferon
•Allergy desensitization injections
•Growth factors
•Interleukins
•Any investigational therapeutic medication

Outcomes

Primary Outcomes

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 Regimen Limiting Toxicity (RLT).

Time Frame: 1 year

Induction of GAA-specific T-cell response

Time Frame: 2 year

Secondary Outcomes

Clinical Response: Radiological response will be determined using the standard WHO response criteria. Based on serial magnetic resonance imaging (MRI) scans 2-year progression-free survival (PFS) will be evaluated in an exploratory manner.(3 years)
Biopsy/resection will be encouraged for patients who develop progression. Whenever post-vaccine tumor tissues are available, they will be analyzed for GAA expression status and infiltration of GAA-specific T-cells.(3 years)
Influence of RT on induction of GAA-specific immune response: we will compare the rate and magnitude of GAA-specific immune responses in Cohorts 1 and Cohort 2 using IFN-gamma-enzyme-linked immuno-spot (ELISPOT), and tetramer assays.(3 years)