Adult Diffuse Astrocytoma, Adult Mixed Glioma, Adult Oligoastrocytoma, Adult Oligodendroglioma, Recurrent Adult Brain Tumor
Conditions
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.
Interventions
BIOLOGICALtumor lysate-pulsed autologous dendritic cell vaccine
Given ID
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
Jonsson Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Recruitment details
Dates of recruitment period: 1/2012 - 8/2015 Types of location: Medical clinic
Pre-assignment details
Study enrollment patients must satisfy inclusion criteria, screening evaluations (vital signs, history, physical, neurological exams, Karnofsky Performance Scale, brain MRI , urinalysis, complete blood count, differential, platelets, coagulation tests), underwent leukapheresis, and had suitable Dendritic Cell (DC) Vaccine manufactured for them.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) Patients receive autologous glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 0, 14, and 28.
tumor lysate-pulsed autologous dendritic cell vaccine: Given ID
laboratory biomarker analysis: Correlative studies | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Tumor Progression | 3 |
Baseline characteristics
| Characteristic | Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | — |
|---|---|---|
| Age, Continuous | 46.2 years STANDARD_DEVIATION 21.95 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 5 participants | — |
| Sex: Female, Male Female | 2 Participants | — |
| Sex: Female, Male Male | 3 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 3 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Progression-free Survival (PFS) of Low Grade Glioma Patients Treated With Autologous Dendritic Cells Pulsed With Autologous Tumor Lysate
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.
Time frame: Each case was assessed from the baseline date of surgery to MRI evidence of tumor progression through study completion, up to 44 months.
Population: Completed the maximum time allowed on study without being affected by Tumor Recurrence or Progression.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | Progression-free Survival (PFS) of Low Grade Glioma Patients Treated With Autologous Dendritic Cells Pulsed With Autologous Tumor Lysate | 0-6 months | 0 participants |
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | Progression-free Survival (PFS) of Low Grade Glioma Patients Treated With Autologous Dendritic Cells Pulsed With Autologous Tumor Lysate | 7-12 months | 1 participants |
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | Progression-free Survival (PFS) of Low Grade Glioma Patients Treated With Autologous Dendritic Cells Pulsed With Autologous Tumor Lysate | 13-18 months | 1 participants |
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | Progression-free Survival (PFS) of Low Grade Glioma Patients Treated With Autologous Dendritic Cells Pulsed With Autologous Tumor Lysate | 19-24 months | 1 participants |
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | Progression-free Survival (PFS) of Low Grade Glioma Patients Treated With Autologous Dendritic Cells Pulsed With Autologous Tumor Lysate | 25-30 months | 0 participants |
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | Progression-free Survival (PFS) of Low Grade Glioma Patients Treated With Autologous Dendritic Cells Pulsed With Autologous Tumor Lysate | >30 months | 2 participants |
Secondary
Anti-tumor Immune Responses
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
Time frame: 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.
Population: Quantitative multiplex immuno-histochemical (IHC) of pre-treatment glioma microenvironment of IDH1-specific antibodies
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | Anti-tumor Immune Responses | 1.26 percentage of cells per field | Standard Deviation 1.03 |
| %PD-1+/Field | Anti-tumor Immune Responses | 1.35 percentage of cells per field | Standard Deviation 1.04 |
| %PD-L1+/Field | Anti-tumor Immune Responses | 6.76 percentage of cells per field | Standard Deviation 3.3 |
Secondary
Overall Survival (OS)
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.
Time frame: The timeframe for OS was from the date of surgery until the date of death from any cause, up to 44 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | Overall Survival (OS) | Alive | 5 Participants |
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | Overall Survival (OS) | Deceased | 0 Participants |
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | Overall Survival (OS) | Lost to Follow-Up | 0 Participants |
| Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells) | Overall Survival (OS) | Withdrawal by Subject | 0 Participants |