Vaccine for Patients With Newly Diagnosed or Recurrent Low-Grade Glioma

Phase 2

Completed

Conditions: Adult Diffuse Astrocytoma
Recurrent Adult Brain Tumor
Adult Oligoastrocytoma
Adult Mixed Glioma
Adult Oligodendroglioma

Interventions: Biological: tumor lysate-pulsed autologous dendritic cell vaccine
Other: laboratory biomarker analysis

Brief Summary: The primary purpose of this phase II clinical trial is to determine the safety and effect on survival of patients autologous dendritic cells pulsed with autologous tumor lysate as a treatment for low-grade glioma patients. Other goals of this study are to determine if the vaccine can cause an immune response against patients' cancer cells and slow the growth of their brain tumors

Detailed Description: PRIMARY OBJECTIVES:

I. To determine the 5-year progression-free survival (PFS), using intradermal injections of autologous dendritic cells harvested from peripheral blood precursors and pulsed (co-cultured) with tumor lysate derived from surgical tissues in patients with low-grade gliomas.

SECONDARY OBJECTIVES:

I. To monitor overall survival (OS), and cellular immune responses in brain tumor patients injected with tumor lysate-pulsed dendritic cells.

OUTLINE:

Patients receive tumor lysate-pulsed autologous dendritic cell vaccine intradermally (ID) on days 0, 14, and 28.

Recruitment & Eligibility

Inclusion Criteria

Patients with newly diagnosed or recurrent glioma of World Health Organization (WHO) grade II (astrocytoma, oligodendroglioma, and/or oligoastrocytoma) will be eligible for this protocol
Patients must have had surgical resection at University of California, Los Angeles (UCLA), for which a separate informed consent was signed for the collection of their tumor prior to surgery
After surgery, a pathological diagnosis of low-grade glioma (WHO grade II) will need to be established
Patients must be able to read and understand the informed consent document; patients must sign the informed consent indicating that they are aware of the investigational nature of this study.
Patients must have a Karnofsky performance status (KPS) rating of >= 60 prior to initiating treatment; patients may be enrolled at a KPS of < 60 if it is felt that the patient will have adequate opportunity to recover to a KPS of >= 60 by the initiation of treatment
Hemoglobin >= 9 gm%
Absolute granulocyte count >= 1,500
Platelet count >= 100,000/microliter (uL)
Serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 times institutional normals
Bilirubin =< 1.5mg%
Blood urea nitrogen (BUN) or creatinine =< 1.5 times institutional normals

Exclusion Criteria

Subjects with an active infection
Inability to obtain informed consent because of psychiatric or complicating medical problems
Unstable or severe intercurrent medical or psychiatric conditions as determined by the Investigator
Females of child-bearing potential who are pregnant or lactating or who are not using approved contraception
History of immunodeficiency (e.g., human immunodeficiency virus [HIV]) or autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, vasculitis, polymyositis-dermatomyositis, scleroderma, multiple sclerosis, or juvenile-onset insulin-dependent diabetes) that may be exacerbated by immunotherapy
Subjects with organ allografts
Inability or unwillingness to return for required visits and follow-up exams
Subjects who have an uncontrolled systemic malignancy that is not in remission

Arm && Interventions

Group	Intervention	Description
Treatment (tumor lysate-pulsed autologous dendritic cells)	tumor lysate-pulsed autologous dendritic cell vaccine	Patients receive autologous glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 0, 14, and 28.
Treatment (tumor lysate-pulsed autologous dendritic cells)	laboratory biomarker analysis	Patients receive autologous glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 0, 14, and 28.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) of Low Grade Glioma Patients Treated With Autologous Dendritic Cells Pulsed With Autologous Tumor Lysate	Each case was assessed from the baseline date of surgery to MRI evidence of tumor progression through study completion, up to 44 months.	a Kaplan-Meier curve of the PFS of our trial patients was created and compared to the PFS of control patients matched for tumor grade, recurrence number, IDH1 status and 1p/19q status.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	The timeframe for OS was from the date of surgery until the date of death from any cause, up to 44 months.	From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months. a Kaplan-Meier curve of the OS of our trial patients was created and compared to the OS of control patients matched for tumor grade, recurrence number, IDH1 status and 1p/19q status.
Anti-tumor Immune Responses	Tumor for analysis (CD8, Programmed Death (PD)-1, PD-L1, mutation analysis) was collected at the vaccine-related surgery shortly after enrollment. Blood for analysis (IDH1-specific antibodies) was collected at Day 0, before the first vaccine injection.	Tumor and peripheral blood samples were collected from each of the participants and analyzed for the following biomarkers: IDH1-specific antibodies CD8, PD-1, and PD-L1 content, and correlations among those three biomarkers Mutation analysis/sequencing